Using Computer-extracted Image Phenotypes from Tumors on Breast MRI to Predict Breast Cancer Pathologic Stage

PubMed Central

Burnside, Elizabeth S.; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M.; Sutton, Elizabeth; Brandt, Kathleen R.; Whitman, Gary; Conzen, Suzanne; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl; Huang, Erich; Freymann, John; Kirby, Justin; Morris, Elizabeth; Giger, Maryellen

2015-01-01

Background To demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on MRI can accurately predict pathologic stage. Methods We used a dataset of de-identified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. We analyzed 91 biopsy-proven breast cancer cases with pathologic stage (stage I = 22; stage II = 58; stage III = 11) and surgically proven nodal status (negative nodes = 46, ≥ 1 positive node = 44, no nodes examined = 1). We characterized tumors by (a) radiologist measured size, and (b) CEIP. We built models combining two CEIPs to predict tumor pathologic stage and lymph node involvement, evaluated them in leave-one-out cross-validation with area under the ROC curve (AUC) as figure of merit. Results Tumor size was the most powerful predictor of pathologic stage but CEIPs capturing biologic behavior also emerged as predictive (e.g. stage I+II vs. III demonstrated AUC = 0.83). No size measure was successful in the prediction of positive lymph nodes but adding a CEIP describing tumor “homogeneity,” significantly improved this discrimination (AUC = 0.62, p=.003) over chance. Conclusions Our results indicate that MRI phenotypes show promise for predicting breast cancer pathologic stage and lymph node status. PMID:26619259

[Diagnostic validity of the intraoperative analysis in frozen section of the sentinel lymph node in the surgical management of breast cancer].

PubMed

Bañuelos-Andrío, Luis; Rodríguez-Caravaca, Gil; Argüelles-Pintos, Miguel; Mitjavilla-Casanovas, Mercedes

2014-01-01

The method for intraoperative sentinel lymph node (SLN) evaluation has still not been established in breast cancer staging. This study has evaluated the diagnostic validity and impact of intraoperative analysis using the frozen section (FS) of SLN. We performed a descriptive study of the diagnostic validity of the FS of the SLN in patients with breast cancer and selective sentinel node biopsy (SSNB) from October-2006 to October-2012. The diagnostic validity indexes were evaluated using sensitivity, specificity, positive and negative predictive values and global value. Gold standard was considered as the final histopathological results of the biopsies. A total of 370 patients were studied. Sensitivity and specificity for detection of metastasis by FS in the SLN were 67% and 100%, respectively. Global diagnostic validity was 95%. There was a correlation between detection of metastasis and tumor size (p<0.05). Twelve of the 15 patients with SLN micro-metastases underwent axillary lymph node dissection (ALND). Metastatic lymph nodes were not found in any of them. Intraoperative FS examination of the SLN is a useful and reliable predictor of axillary lymph node staging in patients with initial stages of breast cancer. FS reduces the need for second interventions, at least for most patients who have breast cancer with identifiable positive SLN and unequivocal evidence of positive lymph node disease. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.

PubMed

Roberts, Megan C; Miller, Dave P; Shak, Steven; Petkov, Valentina I

2017-06-01

The Oncotype DX ® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001). Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer

PubMed Central

Chung, Il Yong; Park, Yu Rang; Min, Yul Ha; Lee, Yura; Yoon, Tae In; Sohn, Guiyun; Lee, Sae Byul; Kim, Jisun; Kim, Hee Jeong; Ko, Beom Seok; Son, Byung Ho; Ahn, Sei Hyun

2017-01-01

The aim of this study was to determine the relationship between the body mass index (BMI) at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS) and breast-cancer-specific survival (BCSS) outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029), and BCSS (P = 0.013) in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48) and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99). In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19) and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44). Being underweight (BMI < 18.50 kg/m2) with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00–3.95) and BCSS (HR = 2.24, 95% CI = 1.12–4.47). There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer. PMID:28248981

PREOPERATIVE MRI IMPROVES PREDICTION OF EXTENSIVE OCCULT AXILLARY LYMPH NODE METASTASES IN BREAST CANCER PATIENTS WITH A POSITIVE SENTINEL LYMPH NODE BIOPSY

PubMed Central

Loiselle, Christopher; Eby, Peter R.; Kim, Janice N.; Calhoun, Kristine E.; Allison, Kimberly H.; Gadi, Vijayakrishna K.; Peacock, Sue; Storer, Barry; Mankoff, David A.; Partridge, Savannah C.; Lehman, Constance D.

2014-01-01

Rationale and Objectives To test the ability of quantitative measures from preoperative Dynamic Contrast Enhanced MRI (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have ≥ 4 positive axillary lymph nodes upon completion axillary dissection. Methods and Materials A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (6/2005 – 1/2010). Clinical/pathologic factors, primary lesion size and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (p < 0.05) to predict ≥ 4 positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. Results Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of ≥4 metastatic nodes. Receiver operating characteristic (ROC) curves demonstrated an area under the curve (AUC) of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (p = 0.003). Conclusion Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict presence of metastases in ≥ 4 nodes. DCE-MRI may help identify sentinel node positive patients requiring further localregional therapy. PMID:24331270

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

PubMed

Wang, Na-Na; Yang, Zheng-Jun; Wang, Xue; Chen, Li-Xuan; Zhao, Hong-Meng; Cao, Wen-Feng; Zhang, Bin

2018-04-25

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P < 0.001), and the number of negative sentinel lymph nodes (OR = 0.686, 95% CI 0.575-0.817; P < 0.001) were independent statistically significant predictors of non-sentinel lymph node metastasis. Furthermore, luminal B (OR = 3.311, 95% CI 1.593-6.884; P = 0.001) and HER2 overexpression (OR = 4.308, 95% CI 1.097-16.912; P = 0.036) were independent and statistically significant predictor of non-sentinel lymph node metastasis versus luminal A. A regression model based on the results of multivariate analysis was established to predict the risk of non-sentinel lymph node metastasis, which had an AUC of 0.8188. The model was validated in the validation cohort and showed excellent diagnostic performance. The mathematical prediction model that incorporates five variables including breast cancer molecular subtype demonstrates excellent diagnostic performance in assessing the risk of non-sentinel lymph node metastasis in sentinel lymph node-positive patients. The prediction model could be of help surgeons in evaluating the risk of non-sentinel lymph node involvement for breast cancer patients; however, the model requires further validation in prospective studies.

Radiation Use and Long-Term Survival in Breast Cancer Patients With T1, T2 Primary Tumors and One to Three Positive Axillary Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchholz, Thomas A.; Woodward, Wendy A.; Duan Zhigang

2008-07-15

Background: For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. Methods and Materials: We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). Results: Patients treated with BCT + XRT were younger, were more likelymore » to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. Conclusions: Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.« less

Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.

PubMed

Albain, Kathy S; Barlow, William E; Shak, Steven; Hortobagyi, Gabriel N; Livingston, Robert B; Yeh, I-Tien; Ravdin, Peter; Bugarini, Roberto; Baehner, Frederick L; Davidson, Nancy E; Sledge, George W; Winer, Eric P; Hudis, Clifford; Ingle, James N; Perez, Edith A; Pritchard, Kathleen I; Shepherd, Lois; Gralow, Julie R; Yoshizawa, Carl; Allred, D Craig; Osborne, C Kent; Hayes, Daniel F

2010-01-01

The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes. There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0.006; hazard ratio [HR] 2.64, 95% CI 1.33-5.27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score <18; log-rank p=0.97; HR 1.02, 0.54-1.93), but an improvement in disease-free survival for those with a high recurrence score (score > or =31; log-rank p=0.033; HR 0.59, 0.35-1.01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival. The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence score identifies women who might not benefit from anthracycline-based chemotherapy, despite positive nodes. National Cancer Institute and Genomic Health. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.

PubMed

Pagani, Olivia; Gelber, Shari; Simoncini, Edda; Castiglione-Gertsch, Monica; Price, Karen N; Gelber, Richard D; Holmberg, Stig B; Crivellari, Diana; Collins, John; Lindtner, Jurij; Thürlimann, Beat; Fey, Martin F; Murray, Elizabeth; Forbes, John F; Coates, Alan S; Goldhirsch, Aron

2009-08-01

To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.

Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression

PubMed Central

Santos, Rosângela Portilho Costa; Benvenuti, Ticiana Thomazine; Honda, Suzana Terumi; Del Valle, Paulo Roberto; Katayama, Maria Lucia Hirata; Brentani, Helena Paula; Carraro, Dirce Maria; Rozenchan, Patrícia Bortman; Brentani, Maria Mitzi; de Lyra, Eduardo Carneiro; Torres, César Henrique; Salzgeber, Marcia Batista; Kaiano, Jane Haruko Lima; Góes, João Carlos Sampaio

2010-01-01

Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor. Electronic supplementary material The online version of this article (doi:10.1007/s13277-010-0108-7) contains supplementary material, which is available to authorized users. PMID:20820980

Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression.

PubMed

Santos, Rosângela Portilho Costa; Benvenuti, Ticiana Thomazine; Honda, Suzana Terumi; Del Valle, Paulo Roberto; Katayama, Maria Lucia Hirata; Brentani, Helena Paula; Carraro, Dirce Maria; Rozenchan, Patrícia Bortman; Brentani, Maria Mitzi; de Lyra, Eduardo Carneiro; Torres, César Henrique; Salzgeber, Marcia Batista; Kaiano, Jane Haruko Lima; Góes, João Carlos Sampaio; Folgueira, Maria Aparecida Azevedo Koike

2011-02-01

Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor.

[Definition of nodal volumes in breast cancer treatment and segmentation guidelines].

PubMed

Kirova, Y M; Castro Pena, P; Dendale, R; Campana, F; Bollet, M A; Fournier-Bidoz, N; Fourquet, A

2009-06-01

To assist in the determination of breast and nodal volumes in the setting of radiotherapy for breast cancer and establish segmentation guidelines. Materials and methods. Contrast metarial enhanced CT examinations were obtained in the treatment position in 25 patients to clearly define the target volumes. The clinical target volume (CTV) including the breast, internal mammary nodes, supraclavicular and subclavicular regions and axxilary region were segmented along with the brachial plexus and interpectoral nodes. The following critical organs were also segmented: heart, lungs, contralateral breast, thyroid, esophagus and humeral head. A correlation between clinical and imaging findings and meeting between radiation oncologists and breast specialists resulted in a better definition of irradiation volumes for breast and nodes with establishement of segmentation guidelines and creation of an anatomical atlas. A practical approach, based on anatomical criteria, is proposed to assist in the segmentation of breast and node volumes in the setting of breast cancer treatment along with a definition of irradiation volumes.

Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost.

PubMed

Pellet, Andrew C; Erten, Mujde Z; James, Ted A

2016-06-01

Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. Copyright © 2015 Elsevier Inc. All rights reserved.

[Feasibility analysis of sentinel lymph node biopsy in patients with breast cancer after local lumpectomy].

PubMed

Wang, J; Wang, X; Wang, W Y; Liu, J Q; Xing, Z Y; Wang, X

2016-07-01

To explore the feasibility, safety and clinical application value of sentinel lymph node biopsy(SLNB)in patients with breast cancer after local lumpectomy. Clinical data of 195 patients who previously received local lumpectomy from January 2005 to April 2015 were retrospectively analyzed. All the patients with pathologic stage T1-2N0M0 (T1-2N0M0) breast cancer underwent SLNB. Methylene blue, carbon nanoparticles suspension, technetium-99m-labeled dextran, or in combination were used in the SLNB. The interval from lumpectomy to SLNB was 1-91 days(mean, 18.3 days)and the maximum diameter of tumors before first operation was 0.2-4.5 cm (mean, 1.8 cm). The sentinel lymph node was successfully found in all the cases and the detection rate was 100%. 42 patients received axillary lymph node dissection (ALND), 19 patients had pathologically positive sentinel lymph node, with an accuracy rate of 97.6%, sensitivity of 95.0%, false negative rate of 5.0%, and specificity of 100%, and the false positive rate was 0. Logistic regression analysis suggested that the age of patients was significantly associated with sentinel lymph node metastasis after local lumpectomy. For early breast cancer and after breast tumor biopsy, the influence of local lumpectomy on detection rate and accuracy of sentinel lymph node is not significant. Sentinel lymph node biopsy with appropriately chosen tracing technique may still provide a high detection rate and accuracy.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

PubMed

van Roozendaal, L M; Vane, M L G; van Dalen, T; van der Hage, J A; Strobbe, L J A; Boersma, L J; Linn, S C; Lobbes, M B I; Poortmans, P M P; Tjan-Heijnen, V C G; Van de Vijver, K K B T; de Vries, J; Westenberg, A H; Kessels, A G H; de Wilt, J H W; Smidt, M L

2017-07-01

Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Axillary lymph node metastases in patients with breast carcinomas: assessment with nonenhanced versus uspio-enhanced MR imaging.

PubMed

Memarsadeghi, Mazda; Riedl, Christopher C; Kaneider, Andreas; Galid, Arik; Rudas, Margaretha; Matzek, Wolfgang; Helbich, Thomas H

2006-11-01

To prospectively assess the accuracy of nonenhanced versus ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging for depiction of axillary lymph node metastases in patients with breast carcinoma, with histopathologic findings as reference standard. The study was approved by the university ethics committee; written informed consent was obtained. Twenty-two women (mean age, 60 years; range, 40-79 years) with breast carcinomas underwent nonenhanced and USPIO-enhanced (2.6 mg of iron per kilogram of body weight intravenously administered) transverse T1-weighted and transverse and sagittal T2-weighted and T2*-weighted MR imaging in adducted and elevated arm positions. Two experienced radiologists, blinded to the histopathologic findings, analyzed images of axillary lymph nodes with regard to size, morphologic features, and USPIO uptake. A third independent radiologist served as a tiebreaker if consensus between two readers could not be reached. Visual and quantitative analyses of MR images were performed. Sensitivity, specificity, and accuracy values were calculated. To assess the effect of USPIO after administration, signal-to-noise ratio (SNR) changes were statistically analyzed with repeated-measurements analysis of variance (mixed model) for MR sequences. At nonenhanced MR imaging, of 133 lymph nodes, six were rated as true-positive, 99 as true-negative, 23 as false-positive, and five as false-negative. At USPIO-enhanced MR imaging, 11 lymph nodes were rated as true-positive, 120 as true-negative, two as false-positive, and none as false-negative. In two metastatic lymph nodes in two patients with more than one metastatic lymph node, a consensus was not reached. USPIO-enhanced MR imaging revealed a node-by-node sensitivity, specificity, and accuracy of 100%, 98%, and 98%, respectively. At USPIO-enhanced MR imaging, no metastatic lymph nodes were missed on a patient-by-patient basis. Significant interactions indicating differences in the decrease of SNR values for metastatic and nonmetastatic lymph nodes were found for all sequences (P < .001 to P = .022). USPIO-enhanced MR imaging appears valuable for assessment of axillary lymph node metastases in patients with breast carcinomas and is superior to nonenhanced MR imaging.

Prediction of lymph node involvement in patients with breast tumors measuring 3-5 cm in a middle-income setting: the role of CancerMath.

PubMed

Pijnappel, E N; Bhoo-Pathy, N; Suniza, J; See, M H; Tan, G H; Yip, C H; Hartman, M; Taib, N A; Verkooijen, H M

2014-12-01

In settings with limited resources, sentinel lymph node biopsy (SNB) is only offered to breast cancer patients with small tumors and a low a priori risk of axillary metastases. We investigated whether CancerMath, a free online prediction tool for axillary lymph node involvement, is able to identify women at low risk of axillary lymph node metastases in Malaysian women with 3-5 cm tumors, with the aim to offer SNB in a targeted, cost-effective way. Women with non-metastatic breast cancers, measuring 3-5 cm were identified within the University Malaya Medical Centre (UMMC) breast cancer registry. We compared CancerMath-predicted probabilities of lymph node involvement between women with versus without lymph node metastases. The discriminative performance of CancerMath was tested using receiver operating characteristic (ROC) analysis. Out of 1,017 patients, 520 (51 %) had axillary involvement. Tumors of women with axillary involvement were more often estrogen-receptor positive, progesterone-receptor positive, and human epidermal growth factor receptor (HER)-2 positive. The mean CancerMath score was higher in women with axillary involvement than in those without (53.5 vs. 51.3, p = 0.001). In terms of discrimination, CancerMath performed poorly, with an area under the ROC curve of 0.553 (95 % confidence interval CI 0.518-0.588). Attempts to optimize the CancerMath model by adding ethnicity and HER2 to the model did not improve discriminatory performance. For Malaysian women with tumors measuring 3-5 cm, CancerMath is unable to accurately predict lymph node involvement and is therefore not helpful in the identification of women at low risk of node-positive disease who could benefit from SNB.

The genomic heritage of lymph node metastases: implications for clinical management of patients with breast cancer.

PubMed

Becker, Tyson E; Ellsworth, Rachel E; Deyarmin, Brenda; Patney, Heather L; Jordan, Rick M; Hooke, Jeffrey A; Shriver, Craig D; Ellsworth, Darrell L

2008-04-01

Metastatic breast cancer is an aggressive disease associated with recurrence and decreased survival. To improve outcomes and develop more effective treatment strategies for patients with breast cancer, it is important to understand the molecular mechanisms underlying metastasis. We used allelic imbalance (AI) to determine the molecular heritage of primary breast tumors and corresponding metastases to the axillary lymph nodes. Paraffin-embedded samples from primary breast tumors and matched metastases (n = 146) were collected from 26 patients with node-positive breast cancer involving multiple axillary nodes. Hierarchical clustering was used to assess overall differences in the patterns of AI, and phylogenetic analysis inferred the molecular heritage of axillary lymph node metastases. Overall frequencies of AI were significantly higher (P < 0.01) in primary breast tumors (23%) than in lymph node metastases (15%), and there was a high degree of discordance in patterns of AI between primary breast carcinomas and the metastases. Metastatic tumors in the axillary nodes showed different patterns of chromosomal changes, suggesting that multiple molecular mechanisms may govern the process of metastasis in individual patients. Some metastases progressed with few genomic alterations, while others harbored many chromosomal alterations present in the primary tumor. The extent of genomic heterogeneity in axillary lymph node metastases differs markedly among individual patients. Genomic diversity may be associated with response to adjuvant therapy, recurrence, and survival, and thus may be important in improving clinical management of breast cancer patients.

Regional lymph node staging in breast cancer: the increasing role of imaging and ultrasound-guided axillary lymph node fine needle aspiration.

PubMed

Mainiero, Martha B

2010-09-01

The status of axillary lymph nodes is a key prognostic indicator in patients with breast cancer and helps guide patient management. Sentinel lymph node biopsy is increasingly being used as a less morbid alternative to axillary lymph node dissection. However, when sentinel lymph node biopsy is positive, axillary dissection is typically performed for complete staging and local control. Axillary ultrasound and ultrasound-guided fine needle aspiration (USFNA) are useful for detecting axillary nodal metastasis preoperatively and can spare patients sentinel node biopsy, because those with positive cytology on USFNA can proceed directly to axillary dissection or neoadjuvant chemotherapy. Internal mammary nodes are not routinely evaluated, but when the appearance of these nodes is abnormal on imaging, further treatment or metastatic evaluation may be necessary. Copyright © 2010 Elsevier Inc. All rights reserved.

Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma.

PubMed

Paula, Luciana Marques; De Moraes, Luis Henrique Ferreira; Do Canto, Abaeté Leite; Dos Santos, Laurita; Martin, Airton Abrahão; Rogatto, Silvia Regina; De Azevedo Canevari, Renata

2017-01-01

Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with the development of distant metastases, they did not have predictive potential.

[Is there still a place for extemporaneous exam in breast cancer?].

PubMed

Michy, T; Le Bouëdec, G; Mishellany, F; Penault-Llorca, F; Dauplat, J

2006-02-01

The rise of preoperative diagnosis thanks to new methods of micro and macrobiopsy and the development of sentinel lymph node have dramatically modified the surgical management of patients with breast tumor. The purpose of this study is to know if extemporaneous exams still have a place in the management of breast cancer. Retrospective study which compares the qualitiative evolution of frozen sections in breast tumor at Jean-Perrin center before the practice of percutaneous strereotaxic biopsy and after the training of sentinel lymph node operative biopsy. The results were in favour of a different distribution of anatomocytopathological activity with a decrease of frozen section in breast tumor and an increase of cytological imprints on sentinel nodes. The interest of histologic preoperative diagnosis and the failure of consensus in the sentinel lymph node just leave a restrictive position to frozen section in breast cancer.

Breast Cancer Subtype is Associated With Axillary Lymph Node Metastasis

PubMed Central

He, Zhen-Yu; Wu, San-Gang; Yang, Qi; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Qin; Lin, Huan-Xin

2015-01-01

Abstract The purpose of this study was to assess whether breast cancer subtype (BCS) as determined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 can predict the axillary lymph node metastasis in breast cancer. Patients who received breast conserving surgery or mastectomy and axillary lymph node dissection were identified from 2 cancer centers. The associations between clinicopathological variables and axillary lymph node involvement were evaluated in univariate and multivariate regression analyses. A total of 3471 patients met the inclusion criteria, and 53.0% had axillary lymph node metastases at diagnosis. Patients with hormone receptor (HR)−/human epidermal growth factor receptor 2 (HER2)− subtype had a higher grade disease and the lowest rate of lymphovascular invasion. Univariate and multivariable logistic regression analyses showed that BCS was significantly associated with lymph node involvement. Patients with the HR−/HER2− subtype had the lowest odds of having nodal positivity than those with other BCSs. HR+/HER2− (odds ratio [OR] 1.651, 95% confidence interval [CI]: 1.349–2.021, P < 0.001), HR+/HER2+ (OR 1.958, 95%CI 1.542–2.486, P < 0.001), and HR−/HER2+ (OR 1.525, 95%CI 1.181–1.970, P < 0.001) tumors had higher risk of nodal positivity than the HR−/HER2− subtype. The other independent predictors of nodal metastases included tumor size, tumor grade, and lymphovascular invasion. Breast cancer subtype can predict the presence of axillary lymph node metastasis in breast cancer. HR−/HER2− is associated with a reduced risk of axillary lymph node metastasis compared to other BCSs. Our findings may play an important role in guiding axillary treatment considerations if further confirmed in larger sample size studies. PMID:26632910

Impact of prognostic factors for postmastectomy radiation therapy of breast cancer patients

NASA Astrophysics Data System (ADS)

Simonov, K. A.; Startseva, Zh. A.; Slonimskaya, E. M.; Velikaya, V. V.

2017-09-01

The study included 196 breast cancer patients with stages T1-3N0-3M0. The comprehensive therapy for breast cancer included surgical operation, chemotherapy, and radiotherapy. Multivariate analysis showed that multifocality growth of tumor (p = 0.004), high grade III (p = 0.008), two metastatic lymph nodes (p = 0.02) were associated with an increased risk of regional node failure in the patients with one to three positive lymph nodes. The prognostic models describing the probability of local recurrences of breast cancer were developed for individualization of the radiation therapy tactics. Postmastectomy radiation therapy in the patients with high-risk breast cancer treated with modified radical mastectomy improves locoregional control, breast cancer-specific survival, does not increase late toxicity.

Coexistence of breast cancer metastases and tuberculosis in axillary lymph nodes--a rare association and review of the literature.

PubMed

Salemis, Nikolaos S; Razou, Anna

2010-05-01

The coexistence of metastatic breast cancer and tuberculosis in axillary lymph nodes is very rare. We present the case of a 57-year-old woman with multifocal invasive ductal breast carcinoma in whom the resected axillary nodes were found to harbor both metastatic cancer and tuberculous lymphadenitis. Thorough investigation revealed no evidence of primary tuberculosis elsewhere. A quantiFERON TB-Gold test was positive, indicating latent tuberculosis. The patient was treated with adjuvant chemotherapy antituberculous therapy, radiation and hormonal therapy with aromatase inhibitors. We conclude the possibility of coexistent latent tuberculosis should be kept in mind when granulomatous lesions are identified in axillary lymph nodes with metastatic breast cancer, especially in patients from endemic regions.

Racial Variation in the Uptake of Oncotype DX Testing for Early-Stage Breast Cancer.

PubMed

Roberts, Megan C; Weinberger, Morris; Dusetzina, Stacie B; Dinan, Michaela A; Reeder-Hayes, Katherine E; Carey, Lisa A; Troester, Melissa A; Wheeler, Stephanie B

2016-01-10

Oncotype DX (ODX) is a tumor gene-profiling test that aids in adjuvant chemotherapy decision-making. ODX has the potential to improve quality of care; however, if not equally accessible across racial groups, disparities in cancer care quality may persist or worsen. We examined racial disparities in ODX testing uptake. We used data from the Carolina Breast Cancer Study, phase III, a longitudinal, population-based study of 2,998 North Carolina women who received a diagnosis of breast cancer between 2008 and 2014. Our primary analysis used modified Poisson regression to determine the association between race and whether ODX testing was ordered among two strata: node-negative and node-positive breast cancer. A total of 1,468 women with estrogen receptor-positive, human epidermal growth factor receptor-2-negative, stage I or II breast cancer met inclusion criteria. Black patients had higher-grade and larger tumors, more comorbidities, younger age at diagnosis, and lower socioeconomic status than non-black women. Overall, 42% of women had ODX test results in their pathology reports. Compared with those who did not receive ODX testing, women who received ODX testing tended to be younger and have medium tumor size and grade. Our regression analyses indicated no racial disparities in ODX uptake among node-negative patients. However, racial differences were detected among node-positive patients, with black patients being 46% less likely to receive ODX testing than non-black women (adjusted relative risk, 0.54; 95% CI, 0.35 to 0.84; P = .006). We did not find racial disparities in ODX testing for node-negative patients for whom ODX testing is guideline recommended and widely covered by insurers. However, our findings suggest that a newer, non-guideline-concordant application of ODX testing for node-positive breast cancer was accessed less by black women than by non-black women, reflecting more guideline concordant care among black women. © 2015 by American Society of Clinical Oncology.

Subgroup Economic Evaluation of Radiotherapy for Breast Cancer After Mastectomy.

PubMed

Wan, Xiaomin; Peng, Liubao; Ma, Jinan; Chen, Gannong; Li, Yuanjian

2015-11-01

A recent meta-analysis by the Early Breast Cancer Trialists' Collaborative Group found significant improvements achieved by postmastectomy radiotherapy (PMRT) for patients with breast cancer with 1 to 3 positive nodes (pN1-3). It is unclear whether PMRT is cost-effective for subgroups of patients with positive nodes. To determine the cost-effectiveness of PMRT for subgroups of patients with breast cancer with positive nodes. A semi-Markov model was constructed to estimate the expected lifetime costs, life expectancy, and quality-adjusted life-years for patients receiving or not receiving radiation therapy. Clinical and health utilities data were from meta-analyses by the Early Breast Cancer Trialists' Collaborative Group or randomized clinical trials. Costs were estimated from the perspective of the Chinese society. One-way and probabilistic sensitivity analyses were performed. The incremental cost-effective ratio was estimated as $7984, $4043, $3572, and $19,021 per quality-adjusted life-year for patients with positive nodes (pN+), patients with pN1-3, patients with pN1-3 who received systemic therapy, and patients with >4 positive nodes (pN4+), respectively. According to World Health Organization recommendations, these incremental cost-effective ratios were judged as cost-effective. However, the results of one-way sensitivity analyses suggested that the results were highly sensitive to the relative effectiveness of PMRT (rate ratio). We determined that the results were highly sensitive to the rate ratio. However, the addition of PMRT for patients with pN1-3 in China has a reasonable chance to be cost-effective and may be judged as an efficient deployment of limited health resource, and the risk and uncertainty of PMRT are relatively greater for patients with pN4+. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Breast Cancer. Patients' Survival. Report to the Chairman, Subcommittee on Health and Environment, Committee on Energy and Commerce. House of Representatives.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC.

This monograph examines the effectiveness of adjuvant chemotherapy in premenopausal women with breast cancer that has spread to the lymph nodes under the arm. The review focuses on the issue of how the survival of node-positive breast cancer patients has changed over time. It concludes that the survivability benefits from this treatment need…

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience.

PubMed

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R; Chagpar, Anees B; Killelea, Brigid K; Lannin, Donald R

2017-01-01

Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

Quantification of STAT3 and VEGF expression for molecular diagnosis of lymph node metastasis in breast cancer

PubMed Central

Chen, Yujuan; Liu, Ya; Wang, Yu; Li, Wen; Wang, Xiaolu; Liu, Xuejuan; Chen, Yao; Ouyang, Chibin; Wang, Jing

2017-01-01

Abstract Background: Axillary lymph node metastasis is associated with increased risk of regional recurrence, distant metastasis, and poor survival in breast malignant neoplasm. Expression of signal transducer and activator of transcription 3 (STAT3) is significantly associated with tumor formation, migration, and invasion in various cancers. In addition, vascular endothelial growth factor (VEGF) expression could promote angiogenesis and increase the risk of tumorigenesis. To determine correlations among STAT3 expression, VEGF, and clinicopathological data on lymph node involvement in breast cancer patients after surgery. Methods: The mRNA expression levels of STAT3 and VEGFs were measured in 45 breast invasive ductal carcinoma tissues, 45 peritumoral tissues, and 45 adjacent nontumor tissues by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Postoperative pathological examination revealed explicit axillary lymph node involvement in all patients. Results: Average mRNA levels of STAT3 and VEGFs were the highest in breast invasive ductal carcinoma tissues, followed by peritumoral tissues. High expression of STAT3 showed significant positive correlation with high axillary lymph node involvement and progesterone receptor (PR), VEGF-C, VEGF-D, and vascular endothelial growth factor receptor (VEGFR)-3 expression. The expression levels of STAT3, VEGF-C, and VEGFR-3 were significantly higher in the tumor tissues of patients with axillary lymph node metastasis than in those of patients without the metastasis. Expression levels of VEGF-C and VEGFR-3 were also significantly higher in peritumoral tissues of patients with axillary lymph node metastasis. Positive correlations were found between STAT3 and VEGF-C/-D mRNA levels. Conclusion: These data suggest that STAT3/VEGF-C/VEGFR-3 signaling pathway plays an important role in carcinogenesis and lymph-angiogenesis. Our findings suggest that STAT3 may be a potential molecular biomarker for predicting the involvement of axillary lymph nodes in breast cancer, and therapies targeting STAT3 may be important for preventing breast cancer metastasis. PMID:29137038

The AA genotype of the regulatory BCL2 promoter polymorphism ( 938C>A) is associated with a favorable outcome in lymph node negative invasive breast cancer patients.

PubMed

Bachmann, Hagen S; Otterbach, Friedrich; Callies, Rainer; Nückel, Holger; Bau, Maja; Schmid, Kurt W; Siffert, Winfried; Kimmig, Rainer

2007-10-01

Expression of the antiapoptotic and antiproliferative protein Bcl-2 has been repeatedly shown to be associated with better clinical outcome in breast cancer. We recently showed a novel regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Paraffin-embedded neoplastic and nonneoplastic tissues from 274 patients (161 still alive after a follow-up period of at least 80 months) with primary unilateral invasive breast carcinoma were investigated. Bcl-2 expression of tumor cells was shown by immunohistochemistry; nonneoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (P = 0.030) in lymph node-negative breast cancer patients, whereas no genotype effect could be observed in lymph node-positive cases. Ten-year survival rates were 88.6% for the AA genotype, 78.4% for the AC genotype, and 65.8% for the CC genotype. Multivariable Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for cancer-related death in lymph node-negative breast carcinoma patients (hazard ratio, 3.59; P = 0.032). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome of lymph node-positive but not of lymph node-negative breast cancer patients. In lymph node-negative cases, the (-938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression (P = 0.044) and the survival of patients with Bcl-2-expressing carcinomas (P = 0.006). These results suggest the (-938C>A) polymorphism as a survival prognosticator as well as indicator of a high-risk group within patients with lymph node-negative breast cancer.

Sentinel Lymph Node Biopsy in Early Breast Cancer.

PubMed

Kühn, Thorsten

2011-01-01

The role of axillary surgery for the treatment of primary breast cancer is in a process of constant change. During the last decade, axillary dissection with removal of at least 10 lymph nodes (ALD) was replaced by sentinel lymph node biopsy (SLNB) as a staging procedure. Since then, the indication for SLNB rapidly expanded. Today's surgical strategies aim to minimize the rate of patients with a negative axillary status who undergo ALD. For some subgroups of patients, the indication for SLNB (e.g. multicentric disease, large tumors) or its implication for treatment planning (micrometastatic involvement, neoadjuvant chemotherapy) is being discussed. Although the indication for ALD is almost entirely restricted to patients with positive axillary lymph nodes today, the therapeutic effect of completion ALD is more and more questioned. On the other hand, the diagnostic value of ALD in node-positive patients is discussed. This article reflects today's standards in axillary surgery and discusses open issues on the diagnostic and therapeutic role of SLNB and ALD in the treatment of early breast cancer.

High Expression of CCR7 Predicts Lymph Node Metastasis and Good Prognosis in Triple Negative Breast Cancer.

PubMed

Li, Xuelu; Sun, Siwen; Li, Ning; Gao, Jiyue; Yu, Jing; Zhao, Jinbo; Li, Man; Zhao, Zuowei

2017-01-01

Previous preclinical and clinical studies have reported a positive correlation between the expression of the C-C chemokine receptor 7 (CCR7) and the incidence of lymph node metastasis in breast cancer. However, the prognostic relevance of CCR7 expression in breast cancer remains contradictory till now. The aim of this study is to assess the correlation of the CCR7 expression with other clinicopathological features and prognosis in breast cancer. The CCR7 gene amplification and mRNA expression levels from approximately 3,000 patients were retrieved from human breast cancer databases and analyzed. Furthermore, a total of 188 primary triple negative breast cancer patients were enrolled in this study (diagnosed since January 2009 to January 2013 from the Second Hospital of Dalian Medical University). The protein levels of CCR7 were examined by immunohistochemistry using paraffin-embedded tumor tissues. The analysis of gene amplification and mRNA levels showed the expression of CCR7 in breast cancer correlated with better prognosis. When we compared the CCR7 expressions in different subtypes, the basal-like group showed the highest expression of CCR7 and exhibited a better prognosis. Consistently, Kaplan-Meier analysis of 188 triple negative breast cancer patients showed that the prognosis of patients with positive CCR7 expression was significantly better than those with negative expression (HR=0.642, p=0.0275). Additionally, we also observed a positive correlation between lymph node metastasis and the CCR7 expression (p=0.0096). Our results indicated that elevated CCR7 expression as a marker for increased lymph node metastasis, in addition to serve as an independent prognostic indicator for better overall survival in triple negative breast cancer patients. © 2017 The Author(s). Published by S. Karger AG, Basel.

Sentinel Lymph Nodes for Breast Carcinoma: A Paradigm Shift.

PubMed

Maguire, Aoife; Brogi, Edi

2016-08-01

-Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.

Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis.

PubMed

Ruano Pérez, R; Rebollo Aguirre, A C; García-Talavera San Miguel, P; Díaz Expósito, R; Vidal-Sicart, S; Cordero García, J M; Carrera Salazar, D; Rioja Martín, M E

The role of the selective sentinel node biopsy (SNB) is increasing in relevance in breast cancer women with indication of neoadjuvant chemotherapy (NAC). The Radiosurgery Working Group of the SEMNIM is aware of the necessity of establishing the need for SNB before or after NAC, and also how to manage patients with axillary node-negative or node-positive. There is sufficient data to assess that the SNB with radioisotope techniques are feasible and safe in all these scenarios. An adequate axilla evaluation prior to surgery and the possibility of marking prior to NAC the nodes infiltrated must be the two main pillars to guarantee the success of the SNB. It has been shown that to incorporate the SNB in breast cancer women with indication of NAC increases the rate of a conservative treatment of the axilla that will be a clear benefit for these patients. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

The correlation of extranodal invasion with other prognostic parameters in lymph node positive breast cancer.

PubMed

Altinyollar, Hüseyin; Berberoğlu, Uğur; Gülben, Kaptan; Irkin, Fikret

2007-06-01

The presence of extranodal invasion (ENI) in the metastatic lymph nodes is reported to increase the risk of locoregional recurrence while shortening disease-free and overall survival in patients with breast cancer. In this study the relationship between ENI and other prognostic parameters and survival is investigated. Of 650 patients with breast cancer who were treated in Ankara Oncology Teaching and Research Hospital from 1996 to 2003, 368 (56.6%) had lymph node metastasis. The patients with axillary metastasis were separated into two groups as with and without invasion to lymph node capsule and the surrounding adipose tissue. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. Of 368 patients with axillary metastasis, 135 (36.7%) had ENI. Based on multivariate analysis; the number of metastatic lymph nodes, lymphatic invasion, and tumor necrosis were found to be related with ENI. In the group with ENI, 5-year overall survival rate was 74.8%, compared to 82.3% for patients without ENI which was significantly lower (P = 0.04). In lymph node positive breast cancer with presence of ENI, adverse prognostic parameters are more frequently encountered and has a worse overall survival compared to group without ENI. (c) 2007 Wiley-Liss, Inc.

Breast cancer subtypes can be determinant in the decision making process to avoid surgical axillary staging: A retrospective cohort study.

PubMed

Marrazzo, Antonio; Boscaino, Giovanni; Marrazzo, Emilia; Taormina, Pietra; Toesca, Antonio

2015-09-01

The need for performing axillary lymph-node dissection in early breast cancer when the sentinel lymph node (SLN) is positive has been questioned in recent years. The purpose of this study was to identify a low-risk subgroup of early breast cancer patients in whom surgical axillary staging could be avoided, and to assess the probability of having a positive lymph-node (LN). We evaluated the cohort of 612 consecutive women affected by early breast cancer. We considered age, tumor size, histological grade, vascular invasion, lymphatic invasion and cancer subtype (Luminal A, Luminal B HER-2+, Luminal B HER-2-, HER-2+, and Triple Negative) as variables for univariate and multivariate analyses to assess probability of there being a positive SLN o nonsentinel lymph node (NSLN). Chi-square, Fisher's Exact test and Student's t tests were used to investigate the relationship between variables; whereas logit models were used to estimate and quantify the strength of the relationship among some covariates and SLN or the number of metastases. A significant positive effect of vascular invasion and lymphatic invasion (odds ratios are 4 and 6), and a negative effect of TN (odds ratios is 10) were noted. With respect to positive NSLN, size alone has a significant (positive) effect on tumor presence, but focusing on the number of metastases, also age has a (negative) significant effect. This work shows correlation between subtypes and the probability of having positive SLN. Patients not expressing vascular invasion, lymphatic invasion and, moreover, a triple-negative tumor subtype may be good candidates for breast conservative surgery without axillary surgical staging. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Indications for axillary ultrasound use in breast cancer patients.

PubMed

Joh, Jennifer E; Han, Gang; Kiluk, John V; Laronga, Christine; Khakpour, Nazanin; Lee, M Catherine

2012-12-01

Axillary ultrasound has been adopted for preoperative planning in breast cancer. Our objective was to determine features predictive of abnormal AUS and/or positive axillary node needle biopsy (NBx). Single-institution database of breast cancer patients identified patients with preoperative AUS. Patient characteristics and outcomes were correlated with AUS and NBx. Significant features were identified using univariable and multivariable analysis and correlative statistics. Three hundred thirteen breast cancers were evaluated. Abnormal AUS was demonstrated in 250 cases (80%). Node needle biopsy was performed in 247 cases (79%). Sensitivity and specificity was 93% and 48% for AUS and 86% and 100% for NBx, respectively. Palpable axillary adenopathy was significant in logistic regression model (P < .05). There were positive correlations between tumor grade, clinical T and tumor-node-metastasis stage, invasive ductal carcinoma histology, and inflammatory breast carcinoma with AUS and NBx (P < .05). Clinicopathologic features (grade, histology, tumor size) might help guide judicious use of AUS. Copyright © 2012 Elsevier Inc. All rights reserved.

21-Gene Recurrence Score and Locoregional Recurrence in Node-Positive/ER-Positive Breast Cancer Treated With Chemo-Endocrine Therapy

PubMed Central

Mamounas, Eleftherios P.; Liu, Qing; Paik, Soonmyung; Baehner, Frederick L.; Tang, Gong; Jeong, Jong-Hyeon; Kim, S. Rim; Butler, Steven M.; Jamshidian, Farid; Cherbavaz, Diana B.; Sing, Amy P.; Shak, Steven; Julian, Thomas B.; Lembersky, Barry C.; Wickerham, D. Lawrence; Costantino, Joseph P.; Wolmark, Norman

2017-01-01

Background: The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)–positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. Methods: B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor–positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. Results: There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02). Conclusions: RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy. PMID:28122895

21-Gene Recurrence Score and Locoregional Recurrence in Node-Positive/ER-Positive Breast Cancer Treated With Chemo-Endocrine Therapy.

PubMed

Mamounas, Eleftherios P; Liu, Qing; Paik, Soonmyung; Baehner, Frederick L; Tang, Gong; Jeong, Jong-Hyeon; Kim, S Rim; Butler, Steven M; Jamshidian, Farid; Cherbavaz, Diana B; Sing, Amy P; Shak, Steven; Julian, Thomas B; Lembersky, Barry C; Wickerham, D Lawrence; Costantino, Joseph P; Wolmark, Norman

2017-01-01

The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02). RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ].

PubMed

Ruvalcaba-Limón, Eva; de Jesús Garduño-Raya, María; Bautista-Piña, Verónica; Trejo-Martínez, Claudia; Maffuz-Aziz, Antonio; Rodríguez-Cuevas, Sergio

2014-01-01

Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.

Lymphatic mapping with fluorescence navigation using indocyanine green and axillary surgery in patients with primary breast cancer.

PubMed

Takeuchi, Megumi; Sugie, Tomoharu; Abdelazeem, Kassim; Kato, Hironori; Shinkura, Nobuhiko; Takada, Masahiro; Yamashiro, Hiroyasu; Ueno, Takayuki; Toi, Masakazu

2012-01-01

The indocyanine green fluorescence (ICGf) navigation method provides real-time lymphatic mapping and sentinel lymph node (SLN) visualization, which enables the removal of SLNs and their associated lymphatic networks. In this study, we investigated the features of the drainage pathways detected with the ICGf navigation system and the order of metastasis in axillary nodes. From April 2008 to February 2010, 145 patients with clinically node-negative breast cancer underwent SLN surgery with ICGf navigation. The video-recorded data from 79 patients were used for lymphatic mapping analysis. We analyzed 145 patients with clinically node-negative breast cancer who underwent SLN surgery with the ICGf navigation system. Fluorescence-positive SLNs were identified in 144 (99%) of 145 patients. Both single and multiple routes to the axilla were identified in 47% of cases using video-recorded lymphatic mapping data. An internal mammary route was detected in 6% of the cases. Skip metastasis to the second or third SLNs was observed in 6 of the 28 node-positive patients. We also examined the strategy of axillary surgery using the ICGf navigation system. We found that, based on the features of nodal involvement, 4-node resection could provide precise information on the nodal status. The ICGf navigation system may provide a different lymphatic mapping result than computed tomography lymphography in clinically node-negative breast cancer patients. Furthermore, it enables the identification of lymph nodes that do not accumulate indocyanine green or dye adjacent to the SLNs in the sequence of drainage. Knowledge of the order of nodal metastasis as revealed by the ICGf system may help to personalize the surgical treatment of axilla in SLN-positive cases, although additional studies are required. © 2012 Wiley Periodicals, Inc.

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.

PubMed

Habel, Laurel A; Shak, Steven; Jacobs, Marlena K; Capra, Angela; Alexander, Claire; Pho, Mylan; Baker, Joffre; Walker, Michael; Watson, Drew; Hackett, James; Blick, Noelle T; Greenberg, Deborah; Fehrenbacher, Louis; Langholz, Bryan; Quesenberry, Charles P

2006-01-01

The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients.

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients

PubMed Central

Habel, Laurel A; Shak, Steven; Jacobs, Marlena K; Capra, Angela; Alexander, Claire; Pho, Mylan; Baker, Joffre; Walker, Michael; Watson, Drew; Hackett, James; Blick, Noelle T; Greenberg, Deborah; Fehrenbacher, Louis; Langholz, Bryan; Quesenberry, Charles P

2006-01-01

Introduction The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. Methods A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. Results After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7–3.9%), 10.7% (95% CI 6.3–14.9%), and 15.5% (95% CI 7.6–22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5–7.9%), 17.8% (95% CI 11.8–23.3%), and 19.9% (95% CI 14.2–25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. Conclusion In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients. PMID:16737553

Regional Nodal Irradiation in Early-Stage Breast Cancer.

PubMed

Whelan, Timothy J; Olivotto, Ivo A; Parulekar, Wendy R; Ackerman, Ida; Chua, Boon H; Nabid, Abdenour; Vallis, Katherine A; White, Julia R; Rousseau, Pierre; Fortin, Andre; Pierce, Lori J; Manchul, Lee; Chafe, Susan; Nolan, Maureen C; Craighead, Peter; Bowen, Julie; McCready, David R; Pritchard, Kathleen I; Gelmon, Karen; Murray, Yvonne; Chapman, Judy-Anne W; Chen, Bingshu E; Levine, Mark N

2015-07-23

Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Primary ectopic breast cancer of the vulva, treated with local excision of the vulva and sentinel lymph node biopsy: a case report.

PubMed

Ishigaki, Takayuki; Toriumi, Yasuo; Nosaka, Ryouko; Kudou, Rei; Imawari, Yoshimi; Kamio, Makiko; Nogi, Hiroko; Shioya, Hisashi; Takeyama, Hiroshi

2017-12-01

Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases have been published in the English-language literature, and there has been no report of primary breast carcinoma of the vulva in Japan. We report a rare case of primary ectopic breast cancer of the vulva that was treated with local excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72-year-old woman who had noticed a right vulvar tumor 10 years earlier. The tumor was excised by the Department of Plastic Surgery of our hospital. The histology of the vulvar tumor revealed an invasive ductal carcinoma of the breast, and immunohistochemical staining of the vulvar specimen showed the tumor cells to be 100% estrogen-receptor-positive and 100% progesterone-receptor-positive. All margins of resection were positive for neoplastic involvement. An additional local excision of the vulva and right inguinal SLNB were performed in our department. The intraoperative frozen section was negative for metastasis, and lymph node dissection was not performed. The final pathology was negative for residual disease, and a partially normal ductal component was present. Adjuvant hormonal therapy with an aromatase inhibitor was indicated post-operatively. The patient was asymptomatic and free of detectable disease at a 6-month follow-up. Due to the rarity of this diagnosis, there are no established guidelines for treatment. Although cases in which SLNB was performed are rare, we consider SLNB to be an effective alternative to inguinal node dissection for ectopic primary breast cancer of the vulva.

Predicting axillary lymph node metastasis from kinetic statistics of DCE-MRI breast images

NASA Astrophysics Data System (ADS)

Ashraf, Ahmed B.; Lin, Lilie; Gavenonis, Sara C.; Mies, Carolyn; Xanthopoulos, Eric; Kontos, Despina

2012-03-01

The presence of axillary lymph node metastases is the most important prognostic factor in breast cancer and can influence the selection of adjuvant therapy, both chemotherapy and radiotherapy. In this work we present a set of kinetic statistics derived from DCE-MRI for predicting axillary node status. Breast DCE-MRI images from 69 women with known nodal status were analyzed retrospectively under HIPAA and IRB approval. Axillary lymph nodes were positive in 12 patients while 57 patients had no axillary lymph node involvement. Kinetic curves for each pixel were computed and a pixel-wise map of time-to-peak (TTP) was obtained. Pixels were first partitioned according to the similarity of their kinetic behavior, based on TTP values. For every kinetic curve, the following pixel-wise features were computed: peak enhancement (PE), wash-in-slope (WIS), wash-out-slope (WOS). Partition-wise statistics for every feature map were calculated, resulting in a total of 21 kinetic statistic features. ANOVA analysis was done to select features that differ significantly between node positive and node negative women. Using the computed kinetic statistic features a leave-one-out SVM classifier was learned that performs with AUC=0.77 under the ROC curve, outperforming the conventional kinetic measures, including maximum peak enhancement (MPE) and signal enhancement ratio (SER), (AUCs of 0.61 and 0.57 respectively). These findings suggest that our DCE-MRI kinetic statistic features can be used to improve the prediction of axillary node status in breast cancer patients. Such features could ultimately be used as imaging biomarkers to guide personalized treatment choices for women diagnosed with breast cancer.

Lymphoscintigraphy Can Select Breast Cancer Patients for Internal Mammary Chain Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindie, Elif, E-mail: elif.hindie@sls.aphp.fr; Department of Nuclear Medicine, CHU de Bordeaux, University of Bordeaux-Segalen, Bordeaux; Groheux, David

2012-07-15

Purpose: Given the risk of undesired toxicity, prophylactic internal mammary (IM) chain irradiation should be offered only to patients at high risk of occult involvement. Lymphoscintigraphy for axillary sentinel node biopsy might help in selecting these patients. Methods and Materials: We reviewed published studies with the following selection criteria: {>=}300 breast cancer patients referred for axilla sentinel node biopsy; scintigraphy performed after peritumoral or intratumoral tracer injection; IM biopsy in the case of IM drainage; and axilla staged routinely independent of IM status. Results: Six prospective studies, for a total of 3,876 patients, fulfilled the inclusion criteria. Parasternal drainage wasmore » present in 792 patients (20.4%). IM biopsy was performed in 644 patients and was positive in 111 (17.2%). Of the positive IM biopsies, 40% were associated with tumors in the lateral breast quadrants. A major difference in the IM positivity rate was found according to the axilla sentinel node status. In patients with negative axilla, the IM biopsy was positive in 7.8% of cases. In patients with positive axilla, however, the IM biopsy was positive in 41% (p < .00001). Because biopsy of multiple IM hot nodes is difficult, the true risk could be even greater, probably close to 50%. Conclusions: Patients with IM drainage on lymphoscintigraphy and a positive axilla sentinel node have a high risk of occult IM involvement. These women should be considered for IM radiotherapy.« less

Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial.

PubMed

Gingras, Isabelle; Holmes, Eileen; De Azambuja, Evandro; Nguyen, David H A; Izquierdo, Miguel; Anne Zujewski, Jo; Inbar, Moshe; Naume, Bjorn; Tomasello, Gianluca; Gralow, Julie R; Wolff, Antonio C; Harris, Lyndsay; Gnant, Michael; Moreno-Aspitia, Alvaro; Piccart, Martine J; Azim, Hatem A

2017-08-01

Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sentinel Lymph Nodes for Breast Carcinoma A Paradigm Shift

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

Context Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. Objective To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. Data Sources Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. Conclusions The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin–stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non–sentinel lymph node involvement. This information is important to decide on further axillary treatment. PMID:27472237

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience

PubMed Central

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R.; Chagpar, Anees B.

2017-01-01

Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1–15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient. PMID:28492062

SLP-2 overexpression could serve as a prognostic factor in node positive and HER2 negative breast cancer.

PubMed

Cao, Wenfeng; Zhang, Bin; Li, Jin; Liu, Yanxue; Liu, Zhihua; Sun, Baocun

2011-12-01

This study aimed to evaluate the utility as a prognostic factor of SLP-2 on the outcome of breast cancer patients. We performed immunohistochemical analysis to examine the SLP-2 expression in a large panel of invasive breast cancer samples. Of the 496 samples, 261 showed overexpression of SLP-2. Importantly, there were significant associations between SLP-2 overexpression and tumour size (p = 0.002), lymph node/distant metastases, clinical stage (p < 0.001), HER2/neu expression (p = 0.003). In addition, there were obvious differences in levels of SLP-2 expression within four molecular subtypes of breast cancer (p = 0.011). High level SLP-2 expression was shown in tumour samples of HER2 and luminal B subtypes, and low level SLP-2 expression was shown in luminal A and triple negative subtypes, suggesting that overexpression of SLP-2 was closely correlated with HER2/neu expression, and that both SLP-2 and HER2/neu can play a role in lymph node/distant metastases of breast cancers. Thus lymph node status, HER2/neu and SLP-2 high-level expression can act as independent prognostic factors. There is an obvious link between SLP-2 and HER2/neu expression. Overexpression of SLP-2 is associated with poorer total survival, especially in lymph node positive coupled with HER2/neu negative patients.

Axillary metastasis as first symptom of occult breast cancer: a case report.

PubMed

Frattaroli, Fabrizio Maria; Carrara, Alessandro; Conte, Anna Maria; Pappalardo, Giuseppe

2002-01-01

Axillary lymph node metastasis from an occult breast carcinoma is a rare occurrence. We report this condition in a 59-year-old woman who presented with a swelling in the right axilla. No breast mass was clinically evident. Mammography, ultrasonography and multiple random fine-needle breast biopsies yielded no pathological findings. No extramammary primary lesions were present. Axillary sampling was performed and histological examination revealed the presence of metastatic adenocarcinoma in three of the 12 dissected lymph nodes. Estrogen receptors were positive and immunohistochemistry pointed to a breast origin. All these data were suggestive of occult breast cancer. The patient refused any further treatment but accepted clinical and radiological follow-up. Eight years later mammography revealed in the same breast a 10-mm nodule containing microcalcifications, which was not evident at physical examination. The patient underwent a lumpectomy. Intraoperative histology was positive for breast carcinoma and complete axillary clearance was performed. Histological examination revealed a lobular invasive breast carcinoma and the presence of micrometastasis in one of the 23 removed lymph nodes. The patient was given radiotherapy to the breast and axilla and tamoxifen. At present, one year after the appearance of the primary tumor, she is free of disease. Based on this case report we suggest an eclectic approach in the management of patients with axillary metastasis from occult breast cancer, depending on the clinical, pathological and biological findings.

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

PubMed

van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

2006-04-01

Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Scientific Impact Recognition Award. Sentinel node staging for breast cancer: intraoperative molecular pathology overcomes conventional histologic sampling errors.

PubMed

Blumencranz, Peter; Whitworth, Pat W; Deck, Kenneth; Rosenberg, Anne; Reintgen, Douglas; Beitsch, Peter; Chagpar, Anees; Julian, Thomas; Saha, Sukamal; Mamounas, Eleftherios; Giuliano, Armando; Simmons, Rache

2007-10-01

When sentinel node dissection reveals breast cancer metastasis, completion axillary lymph node dissection is ideally performed during the same operation. Intraoperative histologic techniques have low and variable sensitivity. A new intraoperative molecular assay (GeneSearch BLN Assay; Veridex, LLC, Warren, NJ) was evaluated to determine its efficiency in identifying significant sentinel lymph node metastases (>.2 mm). Positive or negative BLN Assay results generated from fresh 2-mm node slabs were compared with results from conventional histologic evaluation of adjacent fixed tissue slabs. In a prospective study of 416 patients at 11 clinical sites, the assay detected 98% of metastases >2 mm and 88% of metastasis greater >.2 mm, results superior to frozen section. Micrometastases were less frequently detected (57%) and assay positive results in nodes found negative by histology were rare (4%). The BLN Assay is properly calibrated for use as a stand alone intraoperative molecular test.

Comparison of the diagnostic accuracy of CA27.29 and CA15.3 in primary breast cancer.

PubMed

Gion, M; Mione, R; Leon, A E; Dittadi, R

1999-05-01

A new, fully automated method that measures the breast cancer-associated glycoprotein CA27.29 has become commercially available. The aim of the present study was to compare this CA27.29 assay with the assay that measures CA15.3 in primary breast cancer. The study was performed retrospectively on preoperative serum samples collected from 275 patients with untreated primary breast cancer (154 node positive and 121 node negative). Eighty-three healthy control subjects were also evaluated. CA27.29 was measured using the fully automated Chiron Diagnostics immunochemiluminescent system (ACS:180 BR). CA15.3 was measured with a manual immunoradiometric method (Centocor CA15.3 RIA). In healthy subjects, CA15.3 was significantly higher than CA27.29 (P <0. 0001). On the other hand, in breast cancer patients CA27.29 was higher than CA15.3 (P = 0.013). The mean value found in the control group plus 2 SD was chosen as the positive/negative cutoff point. The overall positivity rates were 34.9% for CA27.29 and 22.5% for CA15.3. The area under the ROC curve was greater (P <0.001) for CA27. 29 (0.72) than for CA15.3 (0.61). Both markers showed a statistically significant, direct relationship, with pathological stage being higher in node-positive than in node-negative cases and in larger than in smaller tumors. Neither CA27.29 nor CA15.3 showed significant associations with age, menopausal status, or tumor receptor status. CA27.29 discriminates primary breast cancer from healthy subjects better than CA15.3, especially in patients with limited disease. Prospective studies are necessary to confirm this conclusion. Copyright 1999 American Association for Clinical Chemistry.

The efficacy of adjuvant trastuzumab in HER-2 positive breast cancer with axillary lymph node metastases according to the treatment duration.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Ozdemir, Nuriye Y; Yazici, Ozan; Zengin, Nurullah; Altundag, Kadri

2014-12-01

Trastuzumab is the first anti-HER-2 humanized monoclonal antibody. The benefit of adjuvant trastuzumab has been shown in randomized phase III trials. Despite trastuzumab being recommended for 52 weeks in the adjuvant treatment of HER-2 positive breast cancer according to the current breast cancer guidelines, there is still no consensus on the optimal duration of adjuvant trastuzumab. The aim of our study is to investigate the efficacy and safety of adjuvant trastuzumab for 9 weeks and 52 weeks in axillary lymph node positive HER-2 positive breast cancer patients. A total of 271 HER-2 and axillary node positive breast cancer patients who received trastuzumab in adjuvant treatment between the years 2005 and 2013 were retrospectively analyzed. Patients with axillary node positive HER-2 positive breast cancer who were non-metastatic were enrolled to the study. Patients were allocated to the 9 week trastuzumab group (n = 155) or the 52 week trastuzumab group (n = 116). Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). Two-sided p values of <0.05 were considered statistically significant. The most important limitation of our manuscript is the retrospective design. The median follow-up time for this analysis was 34 (4-95) months. Patients' clinical and pathological characteristics were well balanced between the two treatment arms. In the 9 week trastuzumab treatment group, the DFS rate was 96.7%, 84.8% and 74.9% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 94.3%, 80.0% and 80.0% (P = 0.76). In the 9 week trastuzumab treatment group, the OS rate was 99.3%, 92.2% and 88.3% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 99.0%, 94.7% and 78.6% (P = 0.99). In both groups, symptomatic heart failure was not reported but asymptomatic left ventricular ejection fraction (LVEF) decline was observed 3 (1.9%) and 18 (15.5%) patients in the 9 week and 52 week trastuzumab treatment groups, respectively (P < 0.001). In our study, the efficacy of trastuzumab for 52 weeks and 9 weeks was similar in node-positive HER-2 positive breast cancer. Cardiotoxicity was significantly increased in the 52 week trastuzumab arm compared to the 9 week trastuzumab arm.

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

PubMed

Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsunuma, Ryoichi, E-mail: r-matsunuma@nifty.com; First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka; Oguchi, Masahiko

2012-07-01

Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and lymore » status. Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.« less

Predictors of axillary lymph node metastases in women with early breast cancer in Singapore.

PubMed

Tan, L G L; Tan, Y Y; Heng, D; Chan, M Y

2005-12-01

The presence of axillary lymph node metastases is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) is an emerging method for the staging of the axilla. It is hoped that with SLNB, the morbidity from axillary lymph node dissection (ALND) can be avoided without compromising the staging and management of early breast cancer. However, only patients found to be SLNB negative benefit from this procedure, as those with positive SLNB may still require ALND. Our objective is to study the various clinico-pathological factors to find predictive factors for axillary lymph node involvement in early breast cancer. It is hoped that with these factors, we will be better able to identify groups of patients most likely to benefit from SLNB. A retrospective study of 380 early breast cancer cases (stage T1 and T2, N0, N1, M0) in women treated in the Department of General Surgery, Tan Tock Seng Hospital, between January 1999 and August 2002, was conducted. Incidence of nodal metastases was correlated with clinico-pathological factors, and analysed by univariate and multivariate analyses. Approximately 35 percent of the 380 cases of early breast cancer had nodal metastases. Multivariate analyses revealed four independent predictors of node positivity: tumour size (p-value equals 0.0001), presence of lymphovascular invasion (p-value is less than 0.0001), tumours with histology other than invasive ductal or lobular carcinoma (p-value equals 0.04), and presence of progesterone receptors (p-value equals 0.05). We have found independent preoperative predictive factors in our local population for the presence of nodal metastases. This information can aid patient selection for SLNB and improve patient counselling.

Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS):a randomised, multicentre, open-label, phase 3 non-inferiority trial

PubMed Central

Donker, Mila; van Tienhoven, Geertjan; Straver, Marieke E; Meijnen, Philip; van de Velde, Cornelis J H; Mansel, Robert E; Cataliotti, Luigi; Westenberg, A Helen; Klinkenbijl, Jean H G; Orzalesi, Lorenzo; Bouma, Willem H; van der Mijle, Huub C J; Nieuwenhuijzen, Grard A P; Veltkamp, Sanne C; Slaets, Leen; Duez, Nicole J; de Graaf, Peter W; van Dalen, Thijs; Marinelli, Andreas; Rijna, Herman; Snoj, Marko; Bundred, Nigel J; Merkus, Jos W S; Belkacemi, Yazid; Petignat, Patrick; Schinagl, Dominic A X; Coens, Corneel; Messina, Carlo G M; Bogaerts, Jan; Rutgers, Emiel J T

2014-01-01

Summary Background If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods Patients with T1–2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Findings Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1–8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00–0·92) after axillary lymph node dissection versus 1·19% (0·31–2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00–5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Interpretation Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1–2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. Funding EORTC Charitable Trust. PMID:25439688

[Adenoid cystic carcinoma of the breast:report of 25 cases].

PubMed

Wei, Lijuan; Liang, Xiaofeng; Li, Shixia; Liu, Juntian

2014-02-01

To explore the clinical features, management approach and treatment outcomes for adenoid cystic carcinoma (ACC) of the breast. The clinicopathological data of 25 patients with breasts ACC treated in our hospital from years 1990 to 2012 were retrospectively reviewed and their prognosis was analyzed. The median age of these 25 patients was 53 years (ranged from 31 to 81 years). With the exception of one male case, all patients were female including 17 cases of postmenopausal women. The most frequent presenting symptom is breast lumps, most (48.0%) were in the upper outer quadrant and areola area of the breast. Core needle biopsy was performed in five patients. The specimen finding were adenoids in three and invasive carcinoma in two cases. Axillary lymph node dissection was performed in 23 patients. Only two patients had histologically positive lymph nodes (3 of 14 and 2 of 20). Expression of ER and PR in 14 cases was detected by immunohistochemistry, showing one PR-positive and three ER-positive cases. The median follow-up of the 25 cases was 118 months (ranged from 12 to 244 months). Two patients died of lung metastases at 3 and 10 years after the surgery, respectively. Due to the complexity of the histology of ACC, adequate sampling of specimens is essential for accurate diagnosis. ACC of the breast is a rare disease with a relatively good prognosis. The low incidence of axillary lymph node metastasis suggests that axillary node dissection is not recommended as a routine procedure. Breast ACC are often with negative ER and PR expression, and the value of adjuvant therapy needs to be further investigated.

Positive versus negative sentinel nodes in early breast cancer patients: axillary or loco-regional relapse and survival. A study spanning 2000-2012.

PubMed

García Fernández, A; Chabrera, C; García Font, M; Fraile, M; Lain, J M; Barco, I; González, C; Gónzalez, S; Reñe, A; Veloso, E; Cassadó, J; Pessarrodona, A; Giménez, N

2013-10-01

Sentinel Node Biopsy (SNB) is a minimally invasive alternative to elective axillary lymph node dissection (ALND) for nodal staging in early breast cancer. The present study was conducted to evaluate prognostic implications of a negative sentinel node (SN) versus a positive SN (followed by completion ALND) in a closely followed-up sample of early breast cancer patients. We studied 889 consecutive breast cancer patients operated for 908 primaries. Patients received adjuvant therapy with chemotherapy, hormone therapy and eventually trastuzumab. Radiation therapy was based on tangential radiation fields that usually included axillary level I. Median follow-up was 47 months. Axillary recurrence was seen in 1.2% (2/162) of positive SN patients, and 0.8% (5/625) of negative SN patients (p = n.s.). There was an overall 3.2% loco-regional failure rate (29/908). Incidence of distant recurrence was 3.3% (23/693) for negative SN patients, and 4.6% (9/196) for positive SN patients (p = n.s.). Overall mortality rate was 4% (8/198) for positive SN patients, while the corresponding specific mortality rate was 2.5% (5/198). For patients with negative SNs, overall mortality was 4.9% (34/693), and the specific mortality was 1.4% (19/693) (p = n.s.). We did not find significant differences in axillary/loco-regional relapse, distant metastases, disease-free interval or mortality between SN negative and SN positive patients, with a follow-up over 4 years. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sentinel Lymph Nodes for Breast Carcinoma: An Update on Current Practice

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1-T2 disease and cN0 who undergo breast conserving surgery and whole-breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2mm). Gross sectioning SLNs at 2 mm intervals and microscopic examination of one H&E-stained section from each SLN block is the preferred method of pathologic evaluation of SLNs. The role and timing of SLN biopsy for patients having neoadjuvant chemotherapy is controversial and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists. PMID:26768036

Impact of Oncotype DX breast Recurrence Score testing on adjuvant chemotherapy use in early breast cancer: Real world experience in Greater Manchester, UK.

PubMed

Loncaster, J; Armstrong, A; Howell, S; Wilson, G; Welch, R; Chittalia, A; Valentine, W J; Bundred, N J

2017-05-01

The National Institute for Health and Clinical Excellence (NICE) recommended the Oncotype DX ® Breast Recurrence Score ® (RS) assay as an option for informing adjuvant chemotherapy decisions in node-negative, oestrogen receptor (ER)+, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer assessed to be at intermediate risk of recurrence based on clinicopathological factors. We evaluated the impact of RS testing on adjuvant chemotherapy decision-making in routine clinical practice in a UK Cancer Network. RS testing was performed in 201 females with newly diagnosed, ER+, HER2-negative, invasive breast cancer who underwent breast surgery with curative intent, were calculated to have a >3% overall survival benefit at 10 years from adjuvant chemotherapy based on PREDICT, and were considered for adjuvant chemotherapy. The impact of RS testing on adjuvant treatment decisions/associated cost was assessed. In all patients, the multi-disciplinary team recommended chemotherapy but the RS result allowed 127/201 patients (63.2%) to avoid unnecessary adjuvant chemotherapy. Amongst ER+, HER2-negative, node-negative patients (eligible for Oncotype DX testing in UK guidelines), 60.3% were spared chemotherapy. In node-positive patients, the assay reduced the use of chemotherapy by 69.2%. The use of RS testing to guide treatment in these 201 patients was associated with significant cost saving (when considering the cost of RS testing for all patients plus chemotherapy and its associated cost for 74 patients). Incorporating RS testing into routine clinical practice for selected node-negative and node-positive breast cancer patients significantly reduces the use of chemotherapy (p < 0.001) with its associated morbidity and costs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative study between ultrasound-guided fine needle aspiration cytology of axillary lymph nodes and sentinel lymph node histopathology in early-stage breast cancer

PubMed Central

Cardoso-Coelho, Lívio Portela; Borges, Rafael Soares; Alencar, Airlane Pereira; Cardoso-Campos-Verdes, Larysse Maira; da Silva-Sampaio, João Paulo; Borges, Umbelina Soares; Gebrim, Luiz Henrique; da Silva, Benedito Borges

2017-01-01

The replacement of sentinel lymph node biopsy (SNB) by ultrasound-guided fine-needle aspiration (US-guided FNA) cytology of axillary lymph nodes is controversial, despite the simplicity and reduced cost of the latter. In the present study, US-guided FNA was performed in 27 patients with early-stage breast cancer for comparison with SNB. Data were analyzed by calculation of sample proportions. Tumor subtypes included invasive ductal carcinoma (85%), invasive lobular carcinoma (7%), and tubular and metaplastic carcinoma (4%). FNA had a sensitivity of 45%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 73%. Axillary lymph node cytology obtained by US guided-FNA in patients with breast cancer had a specificity similar to that of sentinel lymph node histopathology in the presence of axillary node metastases. However, when lymph node cytology is negative, it does not exclude the existence of metastatic implants, due to its low sensitivity in comparison to sentinel lymph node histopathology. PMID:28521436

Enhancing Hormonal Therapy for Breast Cancer by Combination with a Well-Known Approved Pharmaceutical with Little Toxicity

DTIC Science & Technology

2008-07-01

node- positive , and estrogen receptor- positive breast cancer patients : a Southwest Oncology Group study. J Clin Oncol 12(10):2078–2085 7. Woods KE...official Department of the Army position , policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form...ER) positive metastatic breast cancer are limited by the phenomenon of hormonal resistance. We have found that valproic acid (VPA), a pharmaceutical

Number of Negative Lymph Nodes Can Predict Survival after Postmastectomy Radiotherapy According to Different Breast Cancer Subtypes

PubMed Central

Wu, San-Gang; Peng, Fang; Zhou, Juan; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Qin; Lin, Huan-Xin; Bao, Yong; He, Zhen-Yu

2015-01-01

Purpose: To assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with positive axillary lymph nodes after mastectomy and its predictive value for radiotherapy efficacy of different breast cancer subtypes (BCS). Methods: The records of 1,260 breast cancer patients with positive axillary lymph nodes who received mastectomy between January 1998 and December 2007 were reviewed. The prognostic impact and predictive value of the number of NLNs with respect to locoregional recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were analyzed. Results: The median follow-up time was 58 months, and 444 patients (35.2%) received postmastectomy radiotherapy (PMRT). Univariate and multivariate Cox survival analysis indicated the number of NLNs was an independent prognostic factor of LRFS, DFS, and OS. Patients with a higher number of NLNs had better survival. PMRT improved the LRFS of patients with ≤ 8 NLNs ( p < 0.001), while failing to improve the LRFS of patients with > 8 NLNs (p = 0.075). In patients with luminal A subtype, PMRT improved the LRFS, DFS, and OS of patients with ≤ 8 NLNs, but in patients with > 8 NLNs only the LRFS was improved. For patients with luminal B subtype, PMRT only improved the LRFS of patients with ≤ 8 NLNs. The number of NLNs had no predictive value for the efficacy with PMRT in Her2+ and triple-negative subtypes. Conclusions: The number of NLNs is a prognostic indicator in patients with node-positive breast cancer, and it can predict the efficacy of PMRT according to different BCS. PMID:25663944

Detection of Wilms' tumor antigen--specific CTL in tumor-draining lymph nodes of patients with early breast cancer.

PubMed

Gillmore, Roopinder; Xue, Shao-An; Holler, Angelika; Kaeda, Jaspal; Hadjiminas, Dimitri; Healy, Vourneen; Dina, Roberto; Parry, Suzanne C; Bellantuono, Ilaria; Ghani, Yasmeen; Coombes, R Charles; Waxman, Jonathan; Stauss, Hans J

2006-01-01

The Wilms' tumor antigen (WT1) is overexpressed in approximately 90% of breast tumors and, thus, is a potential target antigen for the immunotherapy of breast cancer. We have tested the working hypotheses that WT1 can be immunogenic in patients with breast cancer and can stimulate CTL of sufficient avidity to kill tumor cells. Paired tumor-draining lymph node and peripheral blood samples were analyzed from five HLA-A2-positive patients with stage I/II breast cancer. Fluorescent HLA-A*0201/WT1 tetramers were used to quantify WT1-specific CTL and the functional capacity of the CTL was assessed using cytotoxicity assays and intracellular cytokine staining. WT1 tetramer-binding T cells expanded from all lymph node samples but none of the corresponding peripheral blood samples. Functional assays were carried out on T cells from the patient who had yielded the highest frequency of HLA-A*0201/WT1 tetramer-positive cells. The cytotoxicity assays showed WT1 peptide--specific killing activity of the CTL, whereas intracellular cytokine staining confirmed that the tetramer--positive T cells produced IFN-gamma after stimulation with WT1 peptide. These WT1-specific T cells killed HLA-A2-positive breast cancer cell lines treated with IFN-gamma but no killing was observed with untreated tumor cells. These results show that WT1-specific CTL can be expanded from the tumor-draining lymph nodes of breast cancer patients and that they can display peptide-specific effector function. However, the CTL only killed IFN-gamma-treated tumor targets expressing high levels of HLA-A2 and not tumor cells with low HLA expression. This suggests that induction of autologous WT1-specific CTL may offer only limited tumor protection and that strategies that allow a high level of peptide/MHC complex presentation and/or improve CTL avidity may be required.

Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry.

PubMed

Stemmer, Salomon M; Steiner, Mariana; Rizel, Shulamith; Geffen, David B; Nisenbaum, Bella; Peretz, Tamar; Soussan-Gutman, Lior; Bareket-Samish, Avital; Isaacs, Kevin; Rosengarten, Ora; Fried, Georgeta; McCullough, Debbie; Svedman, Christer; Shak, Steven; Liebermann, Nicky; Ben-Baruch, Noa

2017-01-01

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 ( N  = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated ( n  = 27) and 2.9% in chemotherapy-untreated patients ( n  = 352); P  = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients ( n  = 102) was significantly lower than in untreated patients ( n  = 156) (1.0% vs. 9.7% P  = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated ( n  = 89) and 4.4% in chemotherapy-untreated patients ( n  = 488); P  = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score < 18.

Radionavigated detection of sentinel nodes in breast carcinoma--first experiences of our department.

PubMed

Duchaj, B; Chvalny, P; Vesely, J; Makaiova, I; Durdik, S; Straka, V; Palaj, J; Procka, V; Aksamitova, K; Skraskova, S; Banki, P; Kovacova, S; Galbavy, S

2010-01-01

Biopsy and histological evaluation of sentinel lymphatic node limits the axillary node dissection only in cases of positive histological finding and decreases the occurrence of postoperative complications related to the axillary node dissection. We used radiotracer SentiScint, Medi-Radiopharma Ltd, Hungary and preoperatively administered blue dye--Blue Patenté V, Guebert, Aulnay-Sous-Bios, France. 11 (18%) patients were subdued to deep peritimorous application of radiotracer, 10 (16.4%) to sub/intradermal application over the lesions and n 40 (65.6%) patients the application was sub/intradermal and periareolar. The patients underwent an operation protocol of corresponding quadrantectomy, radionavigated blue-dye sentinel node biopsy and axillary dissection. From May 2006 to June 2008, we examined 61 patients with breast carcinoma. They underwent radionavigated and blue-dye sentinel node biopsy. We detected 57 (93.4%) sentinel nodes with preoperative scintigraphy, of which only 51 (83.6%) were detected peroperatively and underwent histological evaluation. In six (9.8%) cases, the "frozen cut" histology of the primary lesion had shown a benign lesion; hence no sentinel node biopsy or axillary disection was performed. 12 (19.7%) of 51 histologically evaluated sentinel nodes had metastatic invasion. We retrospectively compared the histological fund in sentinel and axillary nodes in patients with metastatic sentinel nodes. In 6 (16.6%) cases, the sentinel node was positive of metastatic invasion but axillary nodes were histologically negative, in 6 (16.6%) cases the sentinel node and axillary nodes were positive for metastatic invasion. We observed falsely negative findings in 3 (8.3%) patients with negative histological fund in the sentinel node, but positive axillary nodes (Tab. 3, Fig. 2, Ref. 11). Full Text (Free, PDF) www.bmj.sk.

Fluorodeoxyglucose--positive internal mammary lymph node in breast cancer patients with silicone implants: is it always metastatic cancer?

PubMed

Soudack, Michalle; Yelin, Alon; Simansky, David; Ben-Nun, Alon

2013-07-01

Patients with breast cancer following mastectomy and silicone implant reconstruction may have enlarged internal mammary lymph nodes with pathological uptake on positron emission tomography with (18)F-fluorodeoxyglucose. This lymphadenopathy is usually considered as metastatic in nature, but has also been reported to be related to other conditions, including silicon migration. The purpose of this study was to determine the rate of metastatic disease in this unique group of patients. A retrospective comparative study of 12 female patients with breast cancer with silicone implants referred for biopsy due to isolated internal mammary lymph node fluorodeoxyglucose uptake on positron emission tomography. Five patients (41.6%) had histological findings related to silicone (n = 4) or non-specific inflammation (n = 1). The remaining 7 (58.3%) had histological evidence of cancer recurrence. There was no significant difference in the fluorodeoxyglucose-standardized uptake value between the two groups. Fluorodeoxyglucose-positive mammary lymph nodes in patients with breast cancer following silicone implant reconstruction may be due to metastatic deposits, non-specific inflammation or silicone migration. Clinical and imaging characteristics are insufficient in differentiating between these conditions. Biopsy is recommended prior to initiation of further treatment.

Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma.

PubMed

Keser, Sevinc H; Kandemir, Nilufer O; Ece, Dilek; Gecmen, Gonca G; Gul, Aylin E; Barisik, Nagehan O; Sensu, Sibel; Buyukuysal, Cagatay; Barut, Figen

2017-04-01

In many cancers, mast cell density (MCD) in the tumor microenvironment is associated with tumor progression and, to a greater extent, angiogenesis. Our study was designed to investigate the correlation between MCD, tumor lymphangiogenesis, and several well-established prognostic parameters in breast cancer. One hundred and four cases of invasive breast carcinoma diagnosed in our clinic between 2007 and 2011 were included. Mast cells and lymphatic vessels were stained with toluidine blue and D2-40, respectively, and their densities were calculated in various areas of tumors and lymph nodes. The variables of MCD and lymphatic vessel density (LVD) were compared using prognostic parameters as well as with each other. As tumor size and volume increased, MCD increased comparably in metastatic lymph nodes; intratumoral and peritumoral LVD also increased. Lymphovascular invasion, lymphatic invasion, perineural invasion, and estrogen receptor positivity were positively related to intratumoral MCD. The relationship between peritumoral MCD and nontumoral breast tissue MCD was statistically significant. Stage was correlated with MCD in metastatic lymph nodes. Metastatic lymph node MCD and intratumoral MCD were also significantly related. Stage, lymphatic invasion, perineural invasion, lymphovascular invasion, and metastatic lymph node MCD were all correlated with intratumoral and/or peritumoral LVD. As nuclear grade increased, intratumoral LVD became higher. In breast carcinoma, MCD, depending on its location, was related to several prognostic parameters. Notably, mast cells may have at least some effect on lymphangiogenesis, which appears to be a predictor of tumor progression. Copyright © 2017. Published by Elsevier Taiwan.

Correlation of SASH1 expression and ultrasonographic features in breast cancer.

PubMed

Gong, Xuchu; Wu, Jinna; Wu, Jian; Liu, Jun; Gu, Hailin; Shen, Hao

2017-01-01

SASH1 is a member of the SH3/SAM adapter molecules family and has been identified as a new tumor suppressor and critical protein in signal transduction. An ectopic expression of SASH1 is associated with decreased cell viability of breast cancer. The aim of this study was to explore the association between SASH1 expression and the ultrasonographic features in breast cancer. A total of 186 patients diagnosed with breast cancer were included in this study. The patients received preoperative ultrasound examination, and the expression of SASH1 was determined using immunohistochemistry methods. Spearman's rank correlation analysis was used to analyze the correlation between SASH1-positive expression and the ultrasonographic features. The positive expression of SASH1 was observed in 63 (33.9%) patients. The positive expression rate of SASH1 was significantly decreased in patients with breast cancer (63/186, 33.9%) compared with controls ( P <0.001). The positive expression rate of SASH1 was significantly decreased in patients with edge burr sign ( P =0.025), lymph node metastasis ( P =0.007), and a blood flow grade of III ( P =0.013) compared with patients without those adverse ultrasonographic features. The expression of SASH1 was negatively correlated with edge burr sign ( P =0.025), lymph node metastasis ( P =0.007), and blood flow grade ( P =0.003) of the patients with breast cancer. The expression of SASH1 was inversely correlated with some critical ultrasonographic features, including edge burr sign, lymph node metastasis, and blood flow grade in breast cancer, and decreased SASH1 expression appears to be associated with adverse clinical and imaging features in breast cancer.

Correlation of SASH1 expression and ultrasonographic features in breast cancer

PubMed Central

Gong, Xuchu; Wu, Jinna; Wu, Jian; Liu, Jun; Gu, Hailin; Shen, Hao

2017-01-01

Objective SASH1 is a member of the SH3/SAM adapter molecules family and has been identified as a new tumor suppressor and critical protein in signal transduction. An ectopic expression of SASH1 is associated with decreased cell viability of breast cancer. The aim of this study was to explore the association between SASH1 expression and the ultrasonographic features in breast cancer. Patients and methods A total of 186 patients diagnosed with breast cancer were included in this study. The patients received preoperative ultrasound examination, and the expression of SASH1 was determined using immunohistochemistry methods. Spearman’s rank correlation analysis was used to analyze the correlation between SASH1-positive expression and the ultrasonographic features. Results The positive expression of SASH1 was observed in 63 (33.9%) patients. The positive expression rate of SASH1 was significantly decreased in patients with breast cancer (63/186, 33.9%) compared with controls (P<0.001). The positive expression rate of SASH1 was significantly decreased in patients with edge burr sign (P=0.025), lymph node metastasis (P=0.007), and a blood flow grade of III (P=0.013) compared with patients without those adverse ultrasonographic features. The expression of SASH1 was negatively correlated with edge burr sign (P=0.025), lymph node metastasis (P=0.007), and blood flow grade (P=0.003) of the patients with breast cancer. Conclusion The expression of SASH1 was inversely correlated with some critical ultrasonographic features, including edge burr sign, lymph node metastasis, and blood flow grade in breast cancer, and decreased SASH1 expression appears to be associated with adverse clinical and imaging features in breast cancer. PMID:28138250

A Prospective Trial on Initiation Factor 4E (eIF4E) Overexpression and Cancer Recurrence in Node-Positive Breast Cancer

PubMed Central

McClusky, Derek R.; Chu, Quyen; Yu, Herbert; DeBenedetti, Arrigo; Johnson, Lester W.; Meschonat, Carol; Turnage, Richard; McDonald, John C.; Abreo, Fleurette; Li, Benjamin D. L.

2005-01-01

Objective: A previous study of patients with stage I to III breast cancer showed that those patients whose tumors were in the highest tertile of eIF4E overexpression experienced a higher risk for recurrence. This study was designed to determine whether high eIF4E overexpression predicts cancer recurrence independent of nodal status by specifically targeting patients with node-positive disease. Methods: The prospective trial was designed to accrue 168 patients with node-positive breast cancer to detect a 2.5-fold increase in risk for recurrence. eIF4E level was quantified by Western blots as x-fold elevated compared with breast tissues from noncancer patients. End points measured were disease recurrence and cancer-related death. Statistical analyses performed include survival analysis by the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. Results: One hundred seventy-four patients with node-positive breast cancer were accrued. All patients fulfilled study inclusion and exclusion criteria, treatment protocol, and surveillance requirements, with a compliance rate >95%. The mean eIF4E elevation was 11.0 ± 7.0-fold (range, 1.4–34.3-fold). Based on previously published data, tertile distribution was as follow: 1) lowest tertile (<7.5-fold) = 67 patients, 2) intermediate tertile (7.5–14-fold) = 54 patients, and 3) highest tertile (>14-fold) = 53 patients. At a median follow up of 32 months, patients with the highest tertile had a statistically significant higher cancer recurrence rate (log-rank test, P = 0.002) and cancer-related death rate (P = 0.036) than the lowest group. Relative risk calculations demonstrated that high eIF4E patients had a 2.4-fold increase in relative risk increase for cancer recurrence (95% confidence interval, 1.2–4.1; P = 0.01). Conclusions: In this prospective study designed to specifically address risk for recurrence in patients with node-positive breast cancer, the patients whose tumors were in the highest tertile of eIF4E overexpression had a 2.4-fold increase in relative risk for cancer recurrence. Therefore, eIF4E overexpression appears to be an independent predictor of a worse outcome in patients with breast cancer independent of nodal status. PMID:16192819

Sentinel lymph node intraoperative imprint cytology in patients with breast cancer-costly or cost effective?

PubMed

Kamiński, Jan P; Case, Doug; Howard-McNatt, Marissa; Geisinger, Kim R; Levine, Edward A

2010-11-01

Sentinel lymph node (SLN) biopsy is now standard of care for breast cancer patients. Intraoperative imprint cytology (IIC) provides results to the surgeon, which may lead to a lymphadenectomy under the same anesthetic when it is positive for metastases. Thus, a positive IIC can spare the patient a second operation and the charges associated with it. The aim of this study is to assess the cost effectiveness of IIC in breast cancer patients. This study evaluated 98 patients who underwent a SLN biopsy between July 2008 and May 2009. The patients were divided into 1 of 3 groups based on the results of IIC and permanent sections: (1) true-negative (TN) IIC, (2) true-positive (TP) IIC, and (3) false-negative (FN) IIC. Total charges for each patient were extracted retrospectively, and nonparametric tests assessed differences in the charges between the three groups. The median total charges per patient for each population were the following: (1) $14,764.62, (2) $19,025.89, and (3) $29,750.64 (P < 0.05). A difference of more than $10,000 exists in total charges per patient between the node-positive population who did not benefit from IIC (FN) and the node-positive population who did benefit from IIC (TP). IIC is a cost-effective evaluation of breast cancer patients. The difference in total charges between the FN and TP groups outweighs the cost of the IIC. In addition to the reduced costs incurred by the patient and the hospital, IIC spares the patient the psychological and physical stress of a second operation.

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

PubMed Central

Goldstein, Lori J.; Gray, Robert; Badve, Sunil; Childs, Barrett H.; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L.; Ravdin, Peter M.; Davidson, Nancy E.; Sledge, George W.; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Sparano, Joseph A.

2008-01-01

Purpose Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. Patients and Methods A sample of 465 patients with hormone receptor (HR) –positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Results Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). Conclusion The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments. PMID:18678838

Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.

PubMed

Goldstein, Lori J; Gray, Robert; Badve, Sunil; Childs, Barrett H; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L; Ravdin, Peter M; Davidson, Nancy E; Sledge, George W; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Sparano, Joseph A

2008-09-01

Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

The Added Value of a Single-photon Emission Computed Tomography-Computed Tomography in Sentinel Lymph Node Mapping in Patients with Breast Cancer and Malignant Melanoma.

PubMed

Bennie, George; Vorster, Mariza; Buscombe, John; Sathekge, Mike

2015-01-01

Single-photon emission computed tomography-computed tomography (SPECT-CT) allows for physiological and anatomical co-registration in sentinel lymph node (SLN) mapping and offers additional benefits over conventional planar imaging. However, the clinical relevance when considering added costs and radiation burden of these reported benefits remains somewhat uncertain. This study aimed to evaluate the possible added value of SPECT-CT and intra-operative gamma-probe use over planar imaging alone in the South African setting. 80 patients with breast cancer or malignant melanoma underwent both planar and SPECT-CT imaging for SLN mapping. We assessed and compared the number of nodes detected on each study, false positive and negative findings, changes in surgical approach and or patient management. In all cases where a sentinel node was identified, SPECT-CT was more accurate anatomically. There was a significant change in surgical approach in 30 cases - breast cancer (n = 13; P 0.001) and malignant melanoma (n = 17; P 0.0002). In 4 cases a node not identified on planar imaging was seen on SPECT-CT. In 16 cases additional echelon nodes were identified. False positives were excluded by SPECT-CT in 12 cases. The addition of SPECT-CT and use of intra-operative gamma-probe to planar imaging offers important benefits in patients who present with breast cancer and melanoma. These benefits include increased nodal detection, elimination of false positives and negatives and improved anatomical localization that ultimately aids and expedites surgical management. This has been demonstrated in the context of industrialized country previously and has now also been confirmed in the setting of a emerging-market nation.

Clinical and economic outcomes associated with adjuvant chemotherapy in elderly patients with early stage operable breast cancer.

PubMed

Sail, Kavita R; Franzini, Luisa; Lairson, David R; Du, Xianglin L

2012-01-01

Breast cancer poses a huge medical burden to the U.S. health-care system, and chemotherapy is an important contributor to cancer costs. This article examines the differences between breast cancer patients who received chemotherapy and those who did not in costs and survival by age, treatment, and axillary node status. We studied a cohort of 23,110 node-positive and 31,572 node-negative women aged 65 years and older diagnosed with incident American Joint Committee on Cancer stage I, II, or IIIA breast cancer between January 1, 1991, and December 31, 2002, using Surveillance Epidemiology and End Results-Medicare data. Total treatment costs and costs associated with the use of chemotherapy were estimated by using the phase-of-care approach. The phase-specific costs were combined to estimate total Medicare payments for cancer care from diagnosis to death. Cox proportional hazard ratio of mortality was used to determine the effectiveness of adjuvant chemotherapy after adjusting for selected patient and tumor characteristics. We used propensity scores to minimize the bias associated with the receipt of adjuvant chemotherapy. Regression-adjusted difference in the average lifetime cost estimates for all node-positive patients receiving chemotherapy was approximately $2438 and was significantly higher (P < 0.05) than for patients not receiving chemotherapy. Mortality was significantly lower in node-positive and node-negative women aged 65 to 74 years receiving chemotherapy. Decision makers can use cost and effectiveness estimates from this study to assess the relative value of chemotherapy in different age groups. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Recent Trends in Chemotherapy Use and Oncologists' Treatment Recommendations for Early-Stage Breast Cancer.

PubMed

Kurian, Allison W; Bondarenko, Irina; Jagsi, Reshma; Friese, Christopher R; McLeod, M Chandler; Hawley, Sarah T; Hamilton, Ann S; Ward, Kevin C; Hofer, Timothy P; Katz, Steven J

2018-05-01

There is growing concern about overtreatment of breast cancer as outcomes have improved over time. However, little is known about how chemotherapy use and oncologists' recommendations have changed in recent years. We surveyed 5080 women (70% response rate) diagnosed with breast cancer between 2013 and 2015 and accrued through two Surveillance, Epidemiology, and End Results registries (Georgia and Los Angeles) about chemotherapy receipt and their oncologists' chemotherapy recommendations. We surveyed 504 attending oncologists (60.3% response rate ) about chemotherapy recommendations in node-negative and node-positive case scenarios. We conducted descriptive statistics of chemotherapy use and patients' report of oncologists' recommendations and used a generalized linear mixed model of chemotherapy use according to time and clinical factors. All statistical tests were two-sided. The analytic sample was 2926 patients with stage I-II, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. From 2013 to 2015, keeping other factors constant, chemotherapy use was estimated to decline from 34.5% (95% confidence interval [CI] = 30.8% to 38.3%) to 21.3% (95% CI = 19.0% to 23.7%, P < .001). Estimated decline in chemotherapy use was from 26.6% (95% CI = 23.0% to 30.7%) to 14.1% (95% CI = 12.0% to 16.3%) for node-negative/micrometastasis patients and from 81.1% (95% CI = 76.6% to 85.0%) to 64.2% (95% CI = 58.6% to 69.6%) for node-positive patients. Use of the 21-gene recurrence score (RS) did not change among node-negative/micrometastasis patients, and increasing RS use in node-positive patients accounted for one-third of the chemotherapy decline. Patients' report of oncologists' recommendations for chemotherapy declined from 44.9% (95% CI = 40.2% to 49.7%) to 31.6% (95% CI = 25.9% to 37.9%), controlling for other factors. Oncologists were much more likely to order RS if patient preferences were discordant with their recommendations (67.4%, 95% CI = 61.7% to 73.0%, vs 17.5%, 95% CI = 13.1% to 22.0%, concordant), and they adjusted recommendations based on patient preferences and RS results. For both node-negative/micrometastasis and node-positive patients, chemotherapy receipt and oncologists' recommendations for chemotherapy declined markedly over time, without substantial change in practice guidelines. Results of ongoing trials will be essential to confirm the quality of this approach to breast cancer care.

Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

PubMed

Wallace, Anne M; Han, Linda K; Povoski, Stephen P; Deck, Kenneth; Schneebaum, Schlomo; Hall, Nathan C; Hoh, Carl K; Limmer, Karl K; Krontiras, Helen; Frazier, Thomas G; Cox, Charles; Avisar, Eli; Faries, Mark; King, Dennis W; Christman, Lori; Vera, David R

2013-08-01

Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance. A total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept. A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept. [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.

Number of negative lymph nodes should be considered for incorporation into staging for breast cancer

PubMed Central

Wu, San-Gang; Wang, Yan; Zhou, Juan; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; He, Zhen-Yu

2015-01-01

This study aimed to investigate the prognostic value of the number of involved lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR), number of negative lymph nodes (NLNs), and log odds of positive lymph nodes (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients who received a mastectomy or breast-conserving surgery were retrospectively reviewed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis showed that pN stage, LNR, number of RLNs, and number of NLNs were significant prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN stage and the number of NLNs were independent prognostic factors for DFS and OS. A higher number of NLNs was associated with higher DFS and OS, and a higher number of involved lymph nodes were associated with poorer DFS and OS. Patients with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed that the NLNs count had a prognostic value in patients with different pT stages and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage and NLNs count have a better prognostic value compared to the RLNs count, LNR, and LODDS. Number of negative lymph nodes should be considered for incorporation into staging for breast cancer. PMID:25973321

Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20.

PubMed

Mamounas, Eleftherios P; Tang, Gong; Fisher, Bernard; Paik, Soonmyung; Shak, Steven; Costantino, Joseph P; Watson, Drew; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2010-04-01

The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen-treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.

Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haffty, Bruce G., E-mail: hafftybg@cinj.rutgers.edu; McCall, Linda M.; Ballman, Karla V.

2016-03-01

Purpose: American College of Surgeons Oncology Group Z1071 was a prospective trial evaluating the false negative rate of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were made at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC. Methods and Materials: Of 756 patients enrolled from July 2009 to June 2011, 685 met all eligibility requirements. Surgical approach, RT, and radiation field design were analyzed based on presenting clinical and pathologic factors. Results: Of 401 node-positive patients, mastectomy was performed inmore » 148 (36.9%), mastectomy with immediate reconstruction in 107 (26.7%), and breast-conserving surgery (BCS) in 146 patients (36.4%). Of the 284 pathologically node-negative patients, mastectomy was performed in 84 (29.6%), mastectomy with immediate reconstruction in 69 (24.3%), and BCS in 131 patients (46.1%). Bilateral mastectomy rates were higher in women undergoing reconstruction than in those without (66.5% vs 32.2%, respectively, P<.0001). Use of internal mammary RT was low (7.8%-11.2%) and did not differ between surgical approaches. Supraclavicular RT rate ranged from 46.6% to 52.2% and did not differ between surgical approaches but was omitted in 193 or 408 node-positive patients (47.3%). Rate of axillary RT was more frequent in patients who remained node-positive (P=.002). However, 22% of patients who converted to node-negative still received axillary RT. Post-mastectomy RT was more frequently omitted after reconstruction than mastectomy (23.9% vs 12.1%, respectively, P=.002) and was omitted in 19 of 107 patients (17.8%) with residual node-positive disease in the reconstruction group. Conclusions: Most clinically node-positive patients treated with NAC undergoing mastectomy receive RT. RT is less common in patients undergoing reconstruction. There is wide variability in RT fields. These practice patterns conflict with expert recommendations and ongoing trial guidelines. There is a significant need for greater uniformity and guidelines regarding RT following NAC.« less

Triple-Negative or HER2-Positive Status Predicts Higher Rates of Locoregional Recurrence in Node-Positive Breast Cancer Patients After Mastectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Shulian; Li Yexiong, E-mail: yexiong@yahoo.com; Song Yongwen

2011-07-15

Purpose: To evaluate the prognostic value of determining estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression in node-positive breast cancer patients treated with mastectomy. Methods and Materials: The records of 835 node-positive breast cancer patients who had undergone mastectomy between January 2000 and December 2004 were analyzed retrospectively. Of these, 764 patients (91.5%) received chemotherapy; 68 of 398 patients (20.9%) with T1-2N1 disease and 352 of 437 patients (80.5%) with T3-4 or N2-3 disease received postoperative radiotherapy. Patients were classified into four subgroups according to hormone receptor (Rec+ or Rec-) and HER2 expression profiles:more » Rec-/HER2- (triple negative; n = 141), Rec-/HER2+ (n = 99), Rec+/HER2+ (n = 157), and Rec+/HER2- (n = 438). The endpoints were the duration of locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival. Results: Patients with triple-negative, Rec-/HER2+, and Rec+/HER2+ expression profiles had a significantly lower 5-year locoregional recurrence-free survival than those with Rec+/HER2- profiles (86.5% vs. 93.6%, p = 0.002). Compared with those with Rec+/HER2+ and Rec+/HER2- profiles, patients with Rec-/HER2- and Rec-/HER2+ profiles had significantly lower 5-year distant metastasis-free survival (69.1% vs. 78.5%, p = 0.000), lower disease-free survival (66.6% vs. 75.6%, p = 0.000), and lower overall survival (71.4% vs. 84.2%, p = 0.000). Triple-negative or Rec-/HER2+ breast cancers had an increased likelihood of relapse and death within the first 3 years after treatment. Conclusions: Triple-negative and HER2-positive profiles are useful markers of prognosis for locoregional recurrence and survival in node-positive breast cancer patients treated with mastectomy.« less

Results of Sentinel Lymph Node Biopsy in Patients with Breast Cancer in 10-Year Own Material of the 4th Military Teaching Hospital with Polyclinic in Wrocław.

PubMed

Kabziński, Piotr; Rac, Jacek; Dorobisz, Tadeusz; Pawłowski, Wiktor; Ziomek, Agnieszka; Chabowski, Mariusz; Janczak, Dawid; Leśniak, Michał; Janczak, Dariusz

2016-05-01

At present, sentinel lymph node biopsy is a standard procedure to assess the advancement of breast cancer and cutaneous melanoma. The aim of the study was to assess the role of the sentinel lymph node biopsy in the treatment of patients with breast cancer in our own material. Analyzed was medical documentation of 258 patients with initially operable breast cancer, qualified for operation with sentinel lymph node biopsy in 2004-2014 in the Department of Surgery of the 4th Military Teaching Hospital. A few hours prior to the planned surgery, radioisotope (technitium-99 sulfur colloid) was applied in the area of tumor or under the areola. 1-2 hours after administering the tracer, the lymphoscintigraphy with the labelling of the sentinel lymph node on the skin was performed. On the basis of the gathered material, obtained were the following parameters: sensitivity - 100%, and specificity - 94.6%. Four cases were false negative (5.5%). 1. Marking the sentinel lymph node in breast cancer, based on the single visualisation method with the use of radioisotope, is a useful and effective technique. 2. The factor influencing the results of the sentinel lymph node biopsy (true positive and negative results and false negative result) was the number of the excised lymph nodes except for the sentinel lymph node. 3. Patients with estrogen receptor expression had often metastases to sentinel lymph node (145 cases - 56%). 4. The false negative rate, i.e. 5.5% in our material, is within the limits of acceptability given in the literature. 5. The sentinel lymph node biopsy performed by the experienced surgical team is a reliable diagnostic tool with a low complication rate.

Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary breast cancer and axillary lymph node metastases as a prognostic factor.

PubMed

Ito, Maiko; Shien, Tadahiko; Omori, Masako; Mizoo, Taeko; Iwamoto, Takayuki; Nogami, Tomohiro; Motoki, Takayuki; Taira, Naruto; Doihara, Hiroyoshi; Miyoshi, Shinichiro

2016-05-01

Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells, and the expression of ALDH1 may be a prognostic factor of poor clinical outcome. The epithelial-mesenchymal transition may produce cells with stem-cell-like properties promoted by transcription factors. We investigated the expression of ALDH1 and transcription factors in both primary and metastatic lesions, and prognostic value of them in breast cancer patients with axillary lymph node metastasis (ALNM). Forty-seven breast cancer patients with ALNM who underwent surgery at Okayama University Hospital from 2002 to 2008 were enrolled. We retrospectively evaluated the levels of ALDH1 and transcription factors, such as Snail, Slug and Twist, in both primary and metastatic lesions by immunohistochemistry. In primary lesions, the positive rate of ALDH1, Snail, Slug and Twist was 19, 49, 40 and 26%, respectively. In lymph nodes, that of ALDH1, Snail, Slug and Twist was 21, 32, 13 and 23%, respectively. The expression of ALDH1 or transcription factors alone was not significantly associated with a poor prognosis. However, co-expression of ALDH1 and Slug in primary lesions was associated with a shorter DFS (P = 0.009). The evaluation of the co-expression of ALDH1 and transcription factors in primary lesions may be useful in prognosis of node-positive breast cancers.

Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer.

PubMed

Nabais, Celso; Figueiredo, Joana; Lopes, Paulina; Martins, Manuela; Araújo, António

2017-04-01

This study aimed to determine the relationship between CK19 mRNA copy number in sentinel lymph nodes (SLN) assessed by one-step nucleic acid amplification (OSNA) technique, and non-sentinel lymph nodes (NSLN) metastization in invasive breast cancer. A model using total tumor load (TTL) obtained by OSNA technique was also constructed to evaluate its predictability. We conducted an observational retrospective study including 598 patients with clinically T1-T3 and node negative invasive breast cancer. Of the 88 patients with positive SLN, 58 patients fulfill the inclusion criteria. In the analyzed group 25.86% had at least one positive NSLN in axillary lymph node dissection. Univariate analysis showed that tumor size, TTL and number of SLN macrometastases were predictive factors for NSLN metastases. In multivariate analysis just the TTL was predictive for positive NSLN (OR 2.67; 95% CI 1.06-6.70; P = 0.036). The ROC curve for the model using TTL alone was obtained and an AUC of 0.805 (95% CI 0.69-0.92) was achieved. For TTL >1.9 × 10 5 copies/μL we got 73.3% sensitivity, 74.4% specificity and 88.9% negative predictive value to predict NSLN metastases. When using OSNA technique to evaluate SLN, NSLN metastases can be predicted intraoperatively. This prediction tool could help in decision for axillary lymph node dissection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Management of Axillary Lymph Nodes in Breast Cancer

PubMed Central

Brenin, David R.; Morrow, Monica; Moughan, Jennifer; Owen, Jean B.; Wilson, J. Frank; Winchester, David P.

1999-01-01

Objective To determine the rates of axillary lymph node dissection (ALND) and axillary irradiation (AI) in patients with breast cancer and to identify the factors influencing them. Summary Background Data Routine performance of ALND in the treatment of breast cancer has become controversial. AI has been proposed as an alternative to ALND, and it has been suggested that AI in addition to ALND may decrease local failure in high-risk patients. Methods A joint study was conducted by the Commission on Cancer of the American College of Surgeons and the American College of Radiology. A total of 17,151 patients with stage I and II breast cancer treated at 819 institutions in 1994 were studied. Results A total of 15,992 patients underwent ALND (93%). The mean ages of patients who did and did not undergo ALND were 60.4 and 73.0 years. Univariate analysis demonstrated significantly decreased rates of ALND for women age 70 or older (86%vs. 97%), patients with clinical T1a tumors (81%vs. 93%), grade I histology (90%vs. 95%), and patients with favorable tumor types (88%vs. 94%). The ALND rate did not vary between palpable and nonpalpable tumors. Multivariate analysis of variables affecting the rate of ALND identified type of surgery, age, tumor size, histology, and payer status as significant. A total of 889 patients received AI. Patients not undergoing ALND were more likely to receive AI (10%vs. 5%). A total of 1.6% of patients with no lymph node metastasis underwent AI, 8.9% of those with one to three positive nodes underwent AI, 24.0% of those with four to nine positive lymph nodes underwent AI, and 29.9% of those with ≥10 positive lymph nodes underwent AI. Multivariate analysis of variables affecting the proportion of patients who received AI and had undergone ALND identified nodal status and type of surgery as significant. Conclusions Axillary lymph node dissection continues to be routinely applied in the treatment of breast cancer, and AI remains underused in patients at high risk for local regional relapse. PMID:10561093

Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials.

PubMed

McGale, P; Taylor, C; Correa, C; Cutter, D; Duane, F; Ewertz, M; Gray, R; Mannu, G; Peto, R; Whelan, T; Wang, Y; Wang, Z; Darby, S

2014-06-21

Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fluorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04). After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy. Cancer Research UK, British Heart Foundation, UK Medical Research Council. Copyright © 2014 EBCTCG. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

Diagnostic and prognostic value of additional SPECT/CT in sentinel lymph node mapping in breast cancer patients.

PubMed

Stanzel, Susanne; Pernthaler, Birgit; Schwarz, Thomas; Bjelic-Radisic, Vesna; Kerschbaumer, Stefan; Aigner, Reingard M

2018-06-01

of the study was to demonstrate the diagnostic and prognostic value of SPECT/CT in sentinel lymph node mapping (SLNM) in patients with invasive breast cancer. 114 patients with invasive breast cancer with clinically negative lymph nodes were included in this retrospective study as they were referred for SLNM with 99m Tc-nanocolloid. Planar image acquisition was accomplished in a one-day or two-day protocol depending on the schedule of the surgical procedure. Low dose SPECT/CT was performed after the planar images. The sentinel lymph node biopsy (SLNB) was considered false negative if a primary recurrence developed within 12 months after SLNB in the axilla from which a tumor-free SLN had been removed. Between December 2009 and December 2011, 114 patients (pts.) underwent SLNM with additional SPECT/CT. Planar imaging identified in 109 pts. 139 SLNs, which were tumor-positive in 42 nodes (n = 41 pts.). SPECT/CT identified in 81 pts. 151 additional SLNs, of which 19 were tumor-positive and led to therapy change (axillary lymph node dissection) in 11 pts. (9.6 %). Of overall 61 tumor-positive SLNs (n = 52 pts.) SPECT/CT detected all, whereas planar imaging detected only 42 of 61 ( P < 0.0001). No patient had lymph node metastasis within 12 months after SLNB in the axilla from which a tumor-free SLN had been removed resulting in a false-negative rate of 0 %. The local relapse rate was 1.8 % leading to a 4-year disease-free survival rate of 90 %. Among patients with breast cancer, the use of SPECT/CT-aided SLNM correlated due to a better anatomical localization and identification of planar not visible SLNs with a higher detection rate of SLNs. This led to therapeutic consequences and an excellent false-negative and 4-year disease-free survival rate. Schattauer GmbH.

Medico-economic impact of MSKCC non-sentinel node prediction nomogram for ER-positive HER2-negative breast cancers.

PubMed

Bonsang-Kitzis, Hélène; Mouttet-Boizat, Delphine; Guillot, Eugénie; Feron, Jean-Guillaume; Fourchotte, Virginie; Alran, Séverine; Pierga, Jean-Yves; Cottu, Paul; Lerebours, Florence; Stevens, Denise; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Campana, François; Rouzier, Roman; Reyal, Fabien

2017-01-01

Avoiding axillary lymph node dissection (ALND) for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB) could decrease morbidity with minimal clinical significance. The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN) prediction nomogram for ER+ HER2- breast cancer patients. We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients' characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results. A 0.3 threshold discriminate the type of sentinel node (SN) metastases: 98.8% of patients with pN0(i+) and 91.6% of patients with pN1(mic) had a MSKCC score under 0.3 (false negative rate = 6.4%). If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients. We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+) or pN1(mic) ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3.

Medico-economic impact of MSKCC non-sentinel node prediction nomogram for ER-positive HER2-negative breast cancers

PubMed Central

Guillot, Eugénie; Feron, Jean-Guillaume; Fourchotte, Virginie; Alran, Séverine; Pierga, Jean-Yves; Cottu, Paul; Lerebours, Florence; Stevens, Denise; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Campana, François; Rouzier, Roman; Reyal, Fabien

2017-01-01

Background Avoiding axillary lymph node dissection (ALND) for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB) could decrease morbidity with minimal clinical significance. Purpose The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN) prediction nomogram for ER+ HER2- breast cancer patients. Methods We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients’ characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results. Results A 0.3 threshold discriminate the type of sentinel node (SN) metastases: 98.8% of patients with pN0(i+) and 91.6% of patients with pN1(mic) had a MSKCC score under 0.3 (false negative rate = 6.4%). If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients. Conclusion We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+) or pN1(mic) ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3. PMID:28241044

Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial.

PubMed

Zeidan, Youssef H; Habib, Joyce G; Ameye, Lieveke; Paesmans, Marianne; de Azambuja, Evandro; Gelber, Richard D; Campbell, Ian; Nordenskjöld, Bo; Gutiérez, Jorge; Anderson, Michael; Lluch, Ana; Gnant, Michael; Goldhirsch, Aron; Di Leo, Angelo; Joseph, David J; Crown, John; Piccart-Gebhart, Martine; Francis, Prudence A

2018-06-01

To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P = .005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P = .02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. Our analysis of the BIG 02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. Copyright © 2018 Elsevier Inc. All rights reserved.

Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)

ClinicalTrials.gov

2018-06-19

Breast Adenocarcinoma; Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIB Breast Cancer AJCC v7

PRC2/EED-EZH2 Complex Is Up-Regulated in Breast Cancer Lymph Node Metastasis Compared to Primary Tumor and Correlates with Tumor Proliferation In Situ

PubMed Central

Yu, Hongxiang; Simons, Diana L.; Segall, Ilana; Carcamo-Cavazos, Valeria; Schwartz, Erich J.; Yan, Ning; Zuckerman, Neta S.; Dirbas, Frederick M.; Johnson, Denise L.; Holmes, Susan P.; Lee, Peter P.

2012-01-01

Background Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression. Methodology/Principal Findings We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors. Conclusions/Significance This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens up epigenetic drug development possibilities for the treatment and prevention of lymph node metastasis in breast cancer. PMID:23251464

Use of 99mTc-Tilmanocept as a Single Agent for Sentinel Lymph Node Identification in Breast Cancer: A Retrospective Pilot Study.

PubMed

Unkart, Jonathan T; Wallace, Anne M

2017-09-01

99m Tc-tilmanocept received recent Food and Drug Administration approval for lymphatic mapping in 2013. However, to our knowledge, no prior studies have evaluated the use of 99m Tc-tilmanocept as a single agent in sentinel lymph node (SLN) biopsy in breast cancer. Methods: We executed this retrospective pilot study to assess the ability of 99m Tc-tilmanocept to identify sentinel nodes as a single agent in clinically node-negative breast cancer patients. Patients received a single intradermal injection overlying the tumor of either 18.5 MBq (0.5 mCi) of 99m Tc-tilmanocept on the day of surgery or 74.0 MBq (2.0 mCi) on the day before surgery by a radiologist. Immediate 3-view lymphoscintigraphy was performed. Intraoperatively, SLNs were identified with a portable γ-probe. A node was classified as hot if the count (per second) of the node was more than 3 times the background count. Descriptive statistics are reported. Results: Nineteen patients underwent SLN biopsy with single-agent 99m Tc-tilmanocept. Immediate lymphoscintigraphy identified at least 1 sentinel node in 13 of 17 patients (76.5%). Intraoperatively, at least 1 (mean, 1.7 ± 0.8; range, 1-3) hot node was identified in all patients. Three patients (15.8%) had 1 disease-positive SLN. Conclusion: In this small, retrospective pilot study, 99m Tc-tilmanocept performed well as a single agent for intraoperative sentinel node identification in breast cancer. A larger, randomized clinical trial is warranted to compare 99m Tc-tilmanocept as a single agent with other radiopharmaceuticals for sentinel node identification in breast cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: a systematic review and meta-analysis.

PubMed

Glechner, Anna; Wöckel, Achim; Gartlehner, Gerald; Thaler, Kylie; Strobelberger, Michaela; Griebler, Ursula; Kreienberg, Rolf

2013-03-01

The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients. We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1 year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest. Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing. The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of Lump Size and Nodal Status on Prognosis in Invasive Breast Cancer: Experience from Rural India

PubMed Central

Garg, Monique; Sidhu, Darshan Singh; Singh, Amandeep

2016-01-01

Introduction Breast cancer is now the leading cause of cancer among Indian women. Usually large tumour size and axillary lymph node involvement are linked with adverse outcome and this notion forms the basis of screening programs i.e. early detection. Aim The present study was carried out to analyse relationship between tumour size, lymph node status and there relation with outcome after treatment. Materials and Methods Fifty patients with cytology-proven invasive breast tumours were evaluated for size, clinical and pathologic characteristics of tumour, axillary lymph node status and outcome data recorded on sequential follow-up. Results Mean age of all participated patients was 52.24±10 years. Most common tumour location was in the upper outer quadrant with mean size of primary tumour being 3.31±1.80cm. On pathology number of lymph nodes examined ranged from 10 to 24 and 72% of patients recorded presence of disease in axilla. Significant positive correlation (p<0.013; r2=0.026) between tumour size and axillary lymph node involvement on linear regression. Also an indicative correlation between size and grade of tumour and axillary lymph node status was found with survival from the disease. Conclusion The present study highlights that the size of the primary tumour and the number of positive lymph nodes have an inverse linear relationship with prognosis. Despite advances in diagnostic modalities, evolution of newer markers and genetic typing both size of tumour as T and axillary lymphadenopathy as N form an integral part of TNM staging and are of paramount importance for their role in treatment decisions and illustrate prognosis in patients with invasive breast cancer. PMID:27504343

Solid papillary carcinoma of the breast: A special entity needs to be distinguished from conventional invasive carcinoma avoiding over-treatment.

PubMed

Guo, Shuangping; Wang, Yingmei; Rohr, Joseph; Fan, Chaoliang; Li, Qinglong; Li, Xia; Wang, Zhe

2016-04-01

Solid papillary carcinoma of the breast, a newly-defined entity, is poorly recognized, and its nature and management is still debated. Eleven cases of pure solid papillary breast carcinoma in our archive and 253 cases reported in previous literature were retrospectively analyzed for their clinicopathological features and outcomes. The eleven cases occurred in elderly females. Grossly, all tumors were well-circumscribed and typically composed of solid papillary nodules. The tumor cells were bland-looking with low-grade atypia and mitoses < 5/10HPF. Immunophenotypically, all eleven cases showed positivity for ER and PR, negativity for CK5/6 and HER2, and a low proliferative index of Ki67. Five cases showed scattered positivity for myoepithelial marker p63, and four cases were positive for CK5/6 and CD10 around the nodules, whereas the other cases were completely negative for all myoepithelial markers. Five cases expressed the neuroendocrine marker synaptophysin, and six cases expressed chromogranin. In nine cases, mastectomy and axillary lymph nodes excision were performed, and only one showed micrometastasis in an axillary lymph node. There was no local recurrence or distant metastasis or breast carcinoma related-death during the follow-up periods of 50 months. Out of 253 solid papillary breast carcinomas reported in literature, the percentage of axillary lymph node metastasis was 4/136 (3%), with rare local recurrences and distant metastasis; only three patients died of breast carcinoma. Solid papillary carcinoma of the breast is a rare entity with distinctive clinicopathological features and excellent prognosis and should be distinguished from conventional breast carcinoma to avoid over-treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial

PubMed Central

Hugh, Judith; Hanson, John; Cheang, Maggie Chon U.; Nielsen, Torsten O.; Perou, Charles M.; Dumontet, Charles; Reed, John; Krajewska, Maryla; Treilleux, Isabelle; Rupin, Matthieu; Magherini, Emmanuelle; Mackey, John; Martin, Miguel; Vogel, Charles

2009-01-01

Purpose To investigate the prognostic and predictive significance of subtyping node-positive early breast cancer by immunohistochemistry in a clinical trial of a docetaxel-containing regimen. Methods Pathologic data from a central laboratory were available for 1,350 patients (91%) from the BCIRG 001 trial of docetaxel, doxorubicin, and cyclophosphamide (TAC) versus fluorouracil, doxorubicin, and cyclophosphamide (FAC) for operable node-positive breast cancer. Patients were classified by tumor characteristics as (1) triple negative (estrogen receptor [ER]–negative, progesterone receptor [PR]–negative, HER2/neu [HER2]–negative), (2) HER2 (HER2-positive, ER-negative, PR-negative), (3) luminal B (ER-positive and/or PR-positive and either HER2-positive and/or Ki67high), and (4) luminal A (ER-positive and/or PR-positive and not HER2-positive or Ki67high), and assessed for prognostic significance and response to adjuvant chemotherapy. Results Patients were subdivided into triple negative (14.5%), HER2 (8.5%), luminal B (61.1%), and luminal A (15.9%). Three-year disease-free survival (DFS) rates (P values with luminal B as referent) were 67% (P < .0001), 68% (P = .0008), 82% (referent luminal B), and 91% (P = .0027), respectively, with hazard ratios of 2.22, 2.12, and 0.46. Improved 3-year DFS with TAC was found in the luminal B group (P = .025) and a combined ER-positive/HER2-negative group treated with tamoxifen (P = .041), with a marginal trend in the triple negatives (P = .051) and HER2 (P = .068) subtypes. No DFS advantage was seen in the luminal A population. Conclusion A simple immunopanel can divide breast cancers into biologic subtypes with strong prognostic effects. TAC significantly complements endocrine therapy in patients with luminal B subtype and, in the absence of targeted therapy, is effective in the triple-negative population. PMID:19204205

75 FR 12764 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

..., taxanes such as paclitaxel and docetaxel have emerged as effective chemotherapy agents for breast cancer... with early stage breast cancer. The researchers have developed an immunohistochemistry method for... chemotherapy in NSABP B-28 patients with node-positive breast cancer. J Clin Oncol. 2009 (May 20 Supplement);27...

[Evaluation of green indocyanine interest compared to Technetium in sentinel lymph node detection in breast cancer].

PubMed

Guenane, Y; Gorj, M; Nguyen, V; Revol, M; Mazouz-Dorval, S

2016-12-01

Axillary sentinel lymph node (SN) biopsy by using indocyanine green (ICG) fluorescence for breast cancer is a recent technique. However, compared to Technetium-99m (Tc), which is the reference technique, its efficiency has received little testing. Between December 2013 and January 2014, 40 patients with node-negative breast cancer underwent SN biopsy by injecting sub areolar Tc in preoperative stage and injecting sub areolar ICG in intraoperative stage. SN were previously identified and resected by using ICG coupled with infrared camera. After resection of fluorescent SN, we check its radioactivity with a gamma probe (isotopic method). In case of residual radioactive labeling in the axillary crease, we remove the remaining SN. We have retrospectively analyzed the SN detection concordance rates of these two methods. In total we resected 53 SN, among which 48 (90.6%) were indocyanine green positive and 53 (100%) Tc positive. The remaining 5 SN were all ICG negative and Tc positive. Using ICG has not caused any side effect. SN detection for breast cancer by using ICG fluorescence is a promising, reliable technique which nonetheless requires a degree of expertise before reaching similar results as the Tc technique. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Detection of breast cancer metastasis in sentinel lymph nodes using intra-operative real time GeneSearch BLN Assay in the operating room: results of the Cardiff study.

PubMed

Mansel, Robert E; Goyal, Amit; Douglas-Jones, Anthony; Woods, Victoria; Goyal, Sumit; Monypenny, Ian; Sweetland, Helen; Newcombe, Robert G; Jasani, Bharat

2009-06-01

Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of approximately 2 mm alternating node slabs and 3 additional sections cut at approximately 150 microm interval from each face of the node slab. 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI 86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was performed in a median time of 32 min (range 26-69 min). Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch BLN Assay.

Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients.

PubMed

Chen, Xue; He, Yingjian; Wang, Jiwei; Huo, Ling; Fan, Zhaoqing; Li, Jinfeng; Xie, Yuntao; Wang, Tianfeng; Ouyang, Tao

2018-06-14

Knowledge of the pathology of axillary lymph nodes (ALN) in breast cancer patients is critical for determining their treatment. Ultrasound is the best noninvasive evaluation for the ALN status. However, the correlation between negative ultrasound results and the sentinel lymph nodes (SLN) pathology remains unknown. To test the hypothesis that negative ultrasound results of ALN predict the negative pathology results of SLN in breast cancer patients, we assessed the association between ALN ultrasonography-negative results and the SLN pathology in 3115 patients with breast cancer recruited between October 2010 and April 2016 from a single cancer center, prospective database. Of these patients who met the inclusion criteria, 2317 (74.4%) had no SLN pathological metastasis. In the univariate analysis, other 798 patient with positive SLN tended to be under age 40 and premenopausal, having large tumor sizes (>2 cm), higher histological grade of primary tumor, positive hormone receptors, and negative HER-2 status (P < .05 for all). In the multivariate analysis, menstrual status, tumor size, ER status and histological types of primary tumor remained to be independent predictors for SLN pathological metastasis. The area under curve (AUC) was 0.658 (95% CI = 0.637-0.679), P > .05. In conclusion, only a 74.4% consistency between ALN ultrasonography-negative results and negative pathological SLN results, although menstrual status, tumor size, histologic subtypes of primary tumor and ER status were found to be statistically independent predictors of positive SLN among patients negative for ALN ultrasonography. Therefore, the present study suggests that negative ultrasound results of ALN do not adequately predict the negative pathology results of SLN in breast cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Radiotherapy in Italy after conservative treatment of early breast cancer. A survey by the Italian Society of Radiation Oncology (AIRO).

PubMed

Aristei, Cynthia; Amichetti, Maurizio; Ciocca, Mario; Nardone, Luigia; Bertoni, Filippo; Vidali, Cristiana

2008-01-01

The aim of surveys on clinical practice is to stimulate discussion and optimize practice. In this paper the current Italian radiotherapy practice after breast-conserving surgery for early breast cancer is described and adherence to national and international guidelines is assessed. Furthermore, results are compared with an earlier survey in northern Italy and international reports. A multiple-choice questionnaire sent to all 138 Italian radiation oncology centers. 48% of centers responded. Most performed breast-conserving surgery when tumor size was < or =3 cm. All centers routinely performed axillary dissection; 45 carried out sentinel node biopsy followed by axillary dissection when the sentinel node was positive. Most centers re-excised when resection margins were positive. The median interval between surgery and radiotherapy, when chemotherapy was not administered, was 60 days. Adjuvant chemotherapy was preferably administered before radiotherapy. Regional lymph nodes were never irradiated in 10 centers; in all others irradiation depended on the number of positive lymph nodes and/or involvement of axillary fat and/or tumor location in medial quadrants. All centers used standard fractionation; hypofractionated schemes were available in 6. Most centers used 4-6 MV photons. In 59 centers the boost dose of 10 Gy could be increased if margins were not negative. All centers ensured patient setup reproducibility. Treatment planning was computerized in 59 centers. The irradiation dose was prescribed at the ICRU point in 56 centers and portal films were made in 54 centers. Intraoperative radiotherapy was used in 4 centers: for partial breast irradiation in 1 and for boost administration in 3 centers. Although the quality of radiotherapy delivery has improved in Italy in recent years, approaches that do not conform to international standards persist.

Male occult breast cancer with axillary lymph node metastasis as the first manifestation: A case report and literature review.

PubMed

Xu, Ruixin; Li, Jianbin; Zhang, Yingjie; Jing, Hongbiao; Zhu, Youzhe

2017-12-01

Occult breast cancer (OBC) is extremely rare in males with neither symptoms in the breast nor abnormalities upon imaging examination. This current case report presents a young male patient who was diagnosed with male OBC first manifesting as axillary lymph node metastasis. The physical and imaging examination showed no primary lesions in either breasts or in other organs. The pathological results revealed infiltrating ductal carcinoma in the axillary lymph nodes. Immunohistochemical (IHC) staining was negative for estrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)20 and thyroid transcription factor-1 (TTF-1), positive for CK7, gross cystic disease fluid protein-15 (GCDFP-15), epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), and suspicious positive for human epidermal receptor-2 (Her-2). On basis of IHC markers, particularly such as CK7, CK20 and GCDFP-15, and eliminating other malignancies, male OBC was identified in spite of negativity for hormone receptors. The patient underwent left axillary lymph node dissection (ALND) but not mastectomy. After the surgery, the patient subsequently underwent chemotherapy and radiotherapy. The patient is currently being followed up without any signs of recurrence. Carefully imaging examination and pathological analysis were particularly essential in the diagnosis of male OBC. The guidelines for managing male OBC default to those of female OBC and male breast cancer. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Secondary node analysis as an indicator for axillary lymphadenectomy in breast cancer patients.

PubMed

Cremades, Manel; Torres, Mireia; Solà, Montse; Navinés, Jordi; Pascual, Icíar; Mariscal, Antonio; Caballero, Albert; Castellà, Eva; Luna, Miguel Ángel; Julián, Joan Francesc

2017-11-01

Currently, there is no agreement regarding if it would be necessary to perform an axillary lymph node dissection (ALND) in patients who have macrometastases in the sentinel lymph node (SLN). We studied the utility of the secondary node analysis (SN), defined as the following node after the SLN in an anatomical and lymphatic pathway, as a sign of malignant axillary involvement. An observational, retrospective and multicentre study was designed to assess the utility of the SN as a sign of axillary involvement. Among 2273 patients with breast cancer, a valid sample of 283 was obtained representing those who had the SN studied. Main endpoints of our study were: the SLN, the SN and the ALND histological pattern. Sensitivity, specificity and precision of the test were also calculated. SN test, in cases with positive SLN, has a sensitivity of 61.1%, a specificity of 78.7%, a positive predictive value of 45.8% and a negative predictive value of 87.3% with a precision of 74.7%. The study of the SN together with the technique of the SLN allows a more precise staging of the axillary involvement, in patients with breast cancer, than just the SLN technique. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparative study of the immunohistochemical phenotype in breast cancer and its lymph node metastatic location.

PubMed

De la Haba-Rodríguez, Juan R; Ruiz Borrego, Manuel; Gómez España, Auxiliadora; Villar Pastor, Carlos; Japón, Miguel A; Travado, Paulino; Moreno Nogueira, José Andrés; López Rubio, Fernando; Aranda Aguilar, Enrique

2004-01-01

At present, an important part of prognostic information, together with particular treatment strategies in breast cancer, take into account the immunohistochemical phenotype of the primary tumor location. However, the changing heterogeneity intrinsic to neoplastic cells in general leads us to consider the possibility that the expression of these proteins is modified during tumoral development and dissemination. With this hypothesis as a starting point, 60 patients with breast cancer were studied with immunohistochemistry, the expression of estrogen and progestagenic receptors, proliferation through the Ki-67 expression, and the overexpression of HER-2 and p53 in both the primary location and the lymph node metastases. If we consider significant change to be loss (from positive to negative) or gain (negative to positive) of expression in some of the studied determinations, we find that this is produced in 60% of the tumors studied. These results demonstrate the modification of immunohistochemical expression of the proteins studied between the primary tumor location and the lymph node metastases.

The pattern of lymphatic metastasis of breast cancer and its influence on the delineation of radiation fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Jinming; Li Gong; Li Jianbin

2005-03-01

Purpose: The delineation of radiation fields should cover the clinical target volume (CTV) and minimally irradiate the surrounding normal tissues and organs. This study was designed to explore the pattern of lymphatic metastasis of breast cancer and indications for radiotherapy after radical or modified radical mastectomy and to discuss the rational delineation of radiation fields. Methods and materials: Between September 1980 and December 2003, 78 breast cancer patients receiving extended radical mastectomy in the Margottini model and 61 cases with complete data were analyzed to investigate the internal mammary lymphatic metastatic status. Between March 1988 and December 1988, 46 patientsmore » with clinical negative supraclavicular nodes received radical mastectomy plus supraclavicular lymph node dissection. The supraclavicular lymph nodes and axillary lymph nodes were labeled as S and levels I, II, or III, respectively, and examined pathologically. Between January 1996 and April 1999, 412 patients who had radical or modified radical mastectomy underwent the pathologic examination of axillary or levels I, II, or III nodes. Results: The incidence of internal mammary lymph node metastasis was 24.6%. It was 36.7% for the patients with positive axillary lymph nodes and 12.9% for the patients with negative axillary lymph nodes. All the metastatic internal mammary lymph nodes were located at the first, second, and third intercostal spaces. Skipping metastasis of the supraclavicular and axillary lymph nodes was observed in 3.8% and 8.1% of patients, respectively. Conclusions: According to our data, we suggest that the radiation field for internal mammary lymph nodes should exclude the fourth and fifth intercostal spaces, which may help to reduce the radiation damage to heart. It is unnecessary to irradiate the supraclavicular lymph nodes for the patients with negative axillary level III nodes, even with positive level I and level II nodes.« less

Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in a Randomized Trial of Chemotherapy for Postmenopausal, Node-Positive, Estrogen Receptor-Positive Breast Cancer

PubMed Central

Albain, Kathy S.; Barlow, William E.; Shak, Steven; Hortobagyi, Gabriel N.; Livingston, Robert B.; Yeh, I-Tien; Ravdin, Peter; Bugarini, Roberto; Baehner, Frederick L.; Davidson, Nancy E.; Sledge, George W.; Winer, Eric P.; Hudis, Clifford; Ingle, James N.; Perez, Edith A.; Pritchard, Kathleen I.; Shepherd, Lois; Gralow, Julie R.; Yoshizawa, Carl; Allred, D. Craig; Osborne, C. Kent; Hayes, Daniel F.

2010-01-01

SUMMARY Background The 21-gene Recurrence Score assay (RS) is prognostic for women with node-negative, estrogen receptor (ER)-positive breast cancer (BC) treated with tamoxifen. A low RS predicts little benefit of chemotherapy. For node-positive BC, we investigated whether RS was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher recurrence risks. Methods The phase III trial S8814 for postmenopausal women with node-positive, ER-positive BC showed that CAF chemotherapy prior to tamoxifen (CAF-T) added survival benefit to tamoxifen alone. Optional tumor banking yielded specimens for RS determination by RT-PCR. We evaluated the effect of RS on disease-free survival (DFS) by treatment group (tamoxifen versus CAF-T) using Cox regression adjusting for number of positive nodes. Findings There were 367 specimens (40% of parent trial) with sufficient RNA (tamoxifen, 148; CAF-T, 219). The RS was prognostic in the tamoxifen arm (p=0.006). There was no CAF benefit in the low RS group (logrank p=0.97; HR=1.02, 95% CI (0.54,1.93)), but major DFS improvement for the high RS subset (logrank p=.03; HR=0.59, 95% CI (0.35, 1.01)), adjusting for number of positive nodes. The RS-by-treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), though the cumulative benefit remained at 10 years. Results were similar for overall survival and BC-specific survival. Interpretation In this retrospective analysis, the RS is prognostic for tamoxifen-treated patients with positive nodes and predicts significant CAF benefit in tumors with a high RS. A low RS identifies women who may not benefit from anthracycline-based chemotherapy despite positive nodes. PMID:20005174

Differences in treatment and survival among African-American and Caucasian women with early stage operable breast cancer.

PubMed

Sail, Kavita; Franzini, Luisa; Lairson, David; Du, Xianglin

2012-01-01

To examine racial disparities associated with breast cancer treatment and survival in elderly patients with early stage operable breast cancer. We studied 23,110 women with node-positive and 31,572 women with node-negative tumor who were aged ≥65 with stages I, II, or IIIA breast cancer in 1991-2002 using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Logistic regression analyses were performed to assess the odds of receiving adjuvant chemotherapy and radiation after breast conserving surgery (BCS) for blacks compared to whites. Cox proportional hazard regression models were used to determine the risk of mortality in blacks compared to whites, stratified by types of treatment. Black women with node-positive and node-negative tumors were 25% (odds ratio = 0.75, 95% CI = 0.65-0.87) and 17% (0.83, 0.70-0.99) less likely to receive chemotherapy than white women, after adjusting for patient and tumor characteristics. This relation was not attenuated and remained statistically significant even after adjustment for socioeconomic status. In women with node-negative tumor who did not receive chemotherapy, black women were significantly more likely to die than white women (hazard ratio (HR) = 1.14, 95% CI = 1.04-1.24) after adjusting for patient and tumor characteristics, and comorbidity; and (1.11, 1.01-1.22) after additionally adjusting for socioeconomic status. There were racial disparities between black and white women in receiving adjuvant chemotherapy and radiotherapy following BCS. Higher risk of mortality in black compared to white women was found only in those receiving no chemotherapy. Future studies should explore the root causes of racial disparities beyond treatment factors.

Performance of CT scan of abdomen and pelvis in detecting asymptomatic synchronous metastasis in breast cancer.

PubMed

James, Justin; Teo, Melanie; Ramachandran, Vivekananda; Law, Michael; Stoney, David; Cheng, Michael

2017-10-01

In many centres in Australia, CT scan of abdomen and pelvis (CTAP) is a commonly used staging investigation to detect asymptomatic synchronous metastasis (ASM) in newly diagnosed breast cancer. However, its routine use is not supported by strong evidence either on its cost effectiveness or on specificity. Despite contrary recommendations by international guidelines this staging investigation is widely used among new early breast cancers(EBC). This retrospective study aims to assess the cost effectiveness and usefulness of CTAP in new breast cancers. All patients with primary invasive breast cancers who underwent breast cancer treatment through Eastern health breast unit during 50-month period from January 2012 were included in the study. All staging CTAP results were reviewed to evaluate its yield, false positive rate and cost of investigation per single positive result. Odds ratio for positive test results were calculated for five possible risk factors (Age less than 40 years, stage III disease, presence of LVI, HER2 positive disease and presence of metastasis in lymph node). 49% (n = 285) of all breast cancer patient underwent staging CTAP which lead to the detection of 4 ASM. (Over all yield of 1%) Overall false positive rate was 15% because of 42 indeterminate results needing further tests. Based merely on approved billing rates this amounted to $ 40733 per single ASM identified. Presence of lymph node metastasis did not increase the chance of positive test result (OR = 1.3; CI:0.13-12.69). Staging CTAP is associated with high incidence of false positive rates and low yield, especially among EBCs. It is desirable to choose this investigation more selectively than currently practiced. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Triple assessment of sentinel lymph node metastasis in early breast cancer using preoperative CTLG, intraoperative fluorescence navigation and OSNA.

PubMed

Mokhtar, Mohamed; Tadokoro, Yukiko; Nakagawa, Misako; Morimoto, Masami; Takechi, Hirokazu; Kondo, Kazuya; Tangoku, Akira

2016-03-01

Sentinel lymph node biopsy (SLNB) became a standard surgical procedure for patients with early breast cancer; however, the optimal method of sentinel lymph node (SLN) identification remains controversial. The current study presents the protocol of our institution for preoperative and intraoperative SLN detection. Fifty female patients with early breast cancer and clinically node-negative axilla were enrolled in this study. All patients underwent preoperative CT lymphography (CTLG), intraoperative SLNB using fluorescence navigation, intraoperative one-step nucleic acid amplification (OSNA) and postoperative hematoxylin and eosin histopathological analysis. Prediction of metastasis by CTLG and detection of metastasis by OSNA were compared to results of histopathology as standard reference. SLN were identified by preoperative CTLG and intraoperative SLNB with fluorescence navigation in all patients, the identification rate was 100 %. SLN metastases were detected as positive by OSNA in 9 patients (18 %), 4 were (++), 4 were (+) and 1 was (+I). SLN metastases were detected as positive by histopathology in 10 patients (20 %). The concordance rate between OSNA and permanent sections was 90 %. The negative predictive value of CTLG was 80 %. Use of CTLG and fluorescence navigation made performing SLNB with high accuracy possible in institutions that cannot use the radioisotope method. OSNA provided accurate intraoperative method, allowing for completion of axillary node dissection during surgery and avoidance of second surgical procedure in patients with positive SLNs, thereby reducing patient distress and, finally, saving hospital costs.

Breast Cancer Nodes Detection Using Ultrasonic Microscale Subarrayed MIMO RADAR

PubMed Central

Siwamogsatham, Siwaruk; Pomalaza-Ráez, Carlos

2014-01-01

This paper proposes the use of ultrasonic microscale subarrayed MIMO RADARs to estimate the position of breast cancer nodes. The transmit and receive antenna arrays are divided into subarrays. In order to increase the signal diversity each subarray is assigned a different waveform from an orthogonal set. High-frequency ultrasonic transducers are used since a breast is considered to be a superficial structure. Closed form expressions for the optimal Neyman-Pearson detector are derived. The combination of the waveform diversity present in the subarrayed deployment and traditional phased-array RADAR techniques provides promising results. PMID:25309591

Radiofrequency Tagged Surgery in Treating Patients With Breast Cancer

ClinicalTrials.gov

2018-06-18

Positive Axillary Lymph Node; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

[Selective biopsy of the sentinel lymph node in breast cancer: without axillary recurrences after a mean follow-up of 4.5 years].

PubMed

Bañuelos Andrío, Luis; Rodríguez Caravaca, Gil; Argüelles Pintos, Miguel; Mitjavilla Casanova, Mercedes

2014-01-01

To analyze the rate of axillary recurrences (AR) in patients with early breast cancer who had not undergone an axillary node dissection (ALND) because of a negative sentinel lymph node biopsy (SLNB). The study includes 173 patients operated on for breast cancer and selective node biopsy. In 32 patients the SLNB was positive and undergone subsequent ALND. We followed up 141 patients with negative SLNB without LDN, with a median follow up of 55 months (range 74-36). The detection rate of SLN was of 99.42%. After a median follow-up of 4.5 years, there were no axillary recurrences. Two patients developed local recurrence, other two patients developed distant metastases and four patients developed a metachronous tumor. Four patients died, none of them because of breast cancer. The results obtained support the SLNB as an accurate technique in the axillary stratification of patients with breast cancer, offering in the cases of negative SLNB a safe axillary control after 4.5 year follow-up. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Efficacy, safety and proper dose analysis of PEGylated granulocyte colony-stimulating factor as support for dose-dense adjuvant chemotherapy in node positive Chinese breast cancer patients.

PubMed

Zhang, Fan; LingHu, RuiXia; Zhan, XingYang; Li, Ruisheng; Feng, Fan; Gao, Xudong; Zhao, Lei; Yang, Junlan

2017-10-03

For high-risk breast cancer patients with positive axillary lymph nodes, dose-dense every-two-week epirubicin/cyclophosphamide-paclitaxel (ddEC-P) regimen is the optimal postoperative adjuvant therapy. However, this regimen is limited by the grade 3/4 neutropenia and febrile neutropenia (FN). There is an urgent need to explore the efficacy, safety and proper dosage of PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) as support for ddEC-P in Chinese breast cancer patients with positive axillary lymph nodes. Prospectively, 40 women with stage IIIA to IIIC breast cancer received ddEC-P ± trastuzumab as adjuvant treatment. PEG-G-CSF was injected subcutaneously in a dose of 6 mg or 3 mg on the 2 th day of each treatment cycle. With administration of PEG-G-CSF, all of the 40 patients completed 8 cycles of ddEC-P ± trastuzumab regimen without dose reductions or treatment delays. Moreover, no FN cases were observed. Further analysis showed that the proper dosage of PEG-G-CSF was 6 mg for ddEC treatment, and 3 mg for ddP treatment. PEG-G-CSF exhibits advantages compared with G-CSF in convenient of administration and tolerance for high risk Chinese breast cancer patients. More importantly, the proper dose of PEG-G-CSF for high risk Chinese breast cancer patients during ddEC-P chemotherapy may be 6 mg for ddEC treatment and 3 mg for ddP treatment.

Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study.

PubMed

Petkov, Valentina I; Miller, Dave P; Howlader, Nadia; Gliner, Nathan; Howe, Will; Schussler, Nicola; Cronin, Kathleen; Baehner, Frederick L; Cress, Rosemary; Deapen, Dennis; Glaser, Sally L; Hernandez, Brenda Y; Lynch, Charles F; Mueller, Lloyd; Schwartz, Ann G; Schwartz, Stephen M; Stroup, Antoinette; Sweeney, Carol; Tucker, Thomas C; Ward, Kevin C; Wiggins, Charles; Wu, Xiao-Cheng; Penberthy, Lynne; Shak, Steven

2016-01-01

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40-84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results ( N =38,568). Unadjusted 5-year BCSM were 0.4% ( n =21,023; 95% confidence interval (CI), 0.3-0.6%), 1.4% ( n =14,494; 95% CI, 1.1-1.7%), and 4.4% ( n =3,051; 95% CI, 3.4-5.6%) for Recurrence Score <18, 18-30, and ⩾31 groups, respectively ( P <0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM ( P <0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N =4,691), 5-year BCSM (unadjusted) was 1.0% ( n =2,694; 95% CI, 0.5-2.0%), 2.3% ( n =1,669; 95% CI, 1.3-4.1%), and 14.3% ( n =328; 95% CI, 8.4-23.8%) for Recurrence Score <18, 18-30, ⩾31 groups, respectively ( P <0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials.

Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101

PubMed Central

Shulman, Lawrence N.; Cirrincione, Constance T.; Berry, Donald A.; Becker, Heather P.; Perez, Edith A.; O'Regan, Ruth; Martino, Silvana; Atkins, James N.; Mayer, Erica; Schneider, Charles J.; Kimmick, Gretchen; Norton, Larry; Muss, Hyman; Winer, Eric P.; Hudis, Clifford

2012-01-01

Purpose The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/cyclophosphamide (AC), but with reduced toxicity. Patients and Methods Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). Results A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P = .77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P = .44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. Conclusion For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome. PMID:22826271

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.

PubMed

von Minckwitz, Gunter; Procter, Marion; de Azambuja, Evandro; Zardavas, Dimitrios; Benyunes, Mark; Viale, Giuseppe; Suter, Thomas; Arahmani, Amal; Rouchet, Nathalie; Clark, Emma; Knott, Adam; Lang, Istvan; Levy, Christelle; Yardley, Denise A; Bines, Jose; Gelber, Richard D; Piccart, Martine; Baselga, Jose

2017-07-13

Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877 .).

Association Between the 21-Gene Recurrence Score Assay and Risk of Locoregional Recurrence in Node-Negative, Estrogen Receptor–Positive Breast Cancer: Results From NSABP B-14 and NSABP B-20

PubMed Central

Mamounas, Eleftherios P.; Tang, Gong; Fisher, Bernard; Paik, Soonmyung; Shak, Steven; Costantino, Joseph P.; Watson, Drew; Geyer, Charles E.; Wickerham, D. Lawrence; Wolmark, Norman

2010-01-01

Purpose The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)–positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). Patients and Methods RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. Results In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen–treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Conclusion Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer. PMID:20065188

Adjuvant tamoxifen influences the lipid profile in breast cancer patients.

PubMed

Lin, Che; Chen, Li-Sheng; Kuo, Shou-Jen; Chen, Dar-Ren

2014-02-01

Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.

[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].

PubMed

Mosbah, R; Raimond, E; Pelissier, A; Hocedez, C; Graesslin, O

2015-05-01

The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Toxoplasmosis presenting as a swelling in the axillary tail of the breast and a palpable axillary lymph node mimicking malignancy: a case report.

PubMed

Siriwardana, Hp Priyantha; Teare, Louise; Kamel, Dia; Inwang, E Reggie

2011-08-04

Lymphadenopathy is a common finding in toxoplasmosis. A breast mass due to toxoplasmosis is very rare, and only a few cases have been reported. We present a case of toxoplasmosis that presented as a swelling in the axillary tail of the breast with a palpable axillary lymph node which mimicked breast cancer. A 45-year-old otherwise healthy Caucasian woman presented with a lump on the lateral aspect of her left breast. Her mother had breast cancer that was diagnosed at the age of 66 years. During an examination, we discovered that our patient had a discrete, firm lump in the axillary tail of her left breast and an enlarged, palpable lymph node in her left axilla. Her right breast and axilla were normal. The clinical diagnosis was malignancy in the left breast. Ultrasound and mammographic examinations of her breast suggested a pathological process but were not conclusive. She had targeted fine-needle aspiration cytology (FNAC) and core biopsy of the lesions. FNAC was indeterminate (C3) but suggested a possibility of toxoplasmosis. The core biopsy was not suggestive of malignancy but showed granulomatous inflammation. She had a wide local excision of the breast lump and an axillary lymph node biopsy. Histopathology and immunohistochemical studies excluded carcinoma or lymphoma but suggested the possibility of intramammary and axillary toxoplasmic lymphadenopathy. The results of Toxoplasma gondii IgM and IgG serology tests were positive, supporting a diagnosis of toxoplasmosis. Toxoplasmosis rarely presents as a pseudotumor of the breast. FNAC and histology are valuable tools for a diagnosis of toxoplasmosis, and serology is an important adjunct for confirmation.

Toxoplasmosis presenting as a swelling in the axillary tail of the breast and a palpable axillary lymph node mimicking malignancy: a case report

PubMed Central

2011-01-01

Introduction Lymphadenopathy is a common finding in toxoplasmosis. A breast mass due to toxoplasmosis is very rare, and only a few cases have been reported. We present a case of toxoplasmosis that presented as a swelling in the axillary tail of the breast with a palpable axillary lymph node which mimicked breast cancer. Case presentation A 45-year-old otherwise healthy Caucasian woman presented with a lump on the lateral aspect of her left breast. Her mother had breast cancer that was diagnosed at the age of 66 years. During an examination, we discovered that our patient had a discrete, firm lump in the axillary tail of her left breast and an enlarged, palpable lymph node in her left axilla. Her right breast and axilla were normal. The clinical diagnosis was malignancy in the left breast. Ultrasound and mammographic examinations of her breast suggested a pathological process but were not conclusive. She had targeted fine-needle aspiration cytology (FNAC) and core biopsy of the lesions. FNAC was indeterminate (C3) but suggested a possibility of toxoplasmosis. The core biopsy was not suggestive of malignancy but showed granulomatous inflammation. She had a wide local excision of the breast lump and an axillary lymph node biopsy. Histopathology and immunohistochemical studies excluded carcinoma or lymphoma but suggested the possibility of intramammary and axillary toxoplasmic lymphadenopathy. The results of Toxoplasma gondii IgM and IgG serology tests were positive, supporting a diagnosis of toxoplasmosis. Conclusions Toxoplasmosis rarely presents as a pseudotumor of the breast. FNAC and histology are valuable tools for a diagnosis of toxoplasmosis, and serology is an important adjunct for confirmation. PMID:21816047

[Expression and clinical significance of KNSL4 in breast cancer].

PubMed

Feng, Yu-Mei; Wan, Yan-Fang; Li, Xiao-Qing; Cao, Xu-Chen; Li, Xi

2006-06-01

Previous screening of breast cancer metastasis-related genes found that the mRNA level of kinesin-like 4 (KNSL4) gene is down-regulated in metastatic lymph nodes as compared with the paired primary breast cancer. This study was to clarify the correlations of KNSL4 mRNA expression to metastasis and prognosis of breast cancer, and explore the correlation of KNSL4 expression to c-erbB-2 expression to explore potential mechanisms of promoting metastasis by KNSL4. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the mRNA level of KNSL4 in 108 specimens of primary breast cancer. The correlations of KNSL4 mRNA level to metastasis and prognosis of the 108 cases were analyzed. Immunohistochemistry was used to assess c-erbB-2 protien expression in 76 out of the 108 cases, and the correlation of KNSL4 expression to c-erbB-2 expression was analyzed. The mRNA level of KNSL4 was significantly lower in the cases at stages iii-iv than in the cases at stages iii-iv (P<0.001), significantly lower in the cases with more than 3 metastatic lymph nodes than in the cases with 0-3 metastatic positive lymph nodes (P<0.01), slightly lower in the cases with negative estrogen receptor or prognesterone receptor than in the cases with positive receptors (P>0.05), lower in the 6 cases with distant metastasis than in the rest cases without distant metastasis within 24 month follow up, lower in the 3 cases with bilateral breast cancer than in other cases with unilateral breast cancer, and significantly lower in c-erbB-2-positive group than in c-erB-2-negative group (P<0.01). The down-regulation of KNSL4 mRNA level is correlated to prognosis of primary breast cancer. It may enhance metastatic ability of breast cancer cells through promoting c-erbB-2 transcription and translation.

Adjuvant radiation trials for high-risk breast cancer patients: adequacy of lymphadenectomy.

PubMed

Silberman, A W; Sarna, G P; Palmer, D

2000-06-01

The recently published, widely publicized adjuvant radiation trials from Denmark and Canada concluded that the addition of postoperative radiotherapy (XRT) to modified radical mastectomy (MRM) and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal patients with breast cancer. Our thesis is that adequate lymphadenectomies were not performed in either study. Consequently, the conclusion to these studies is not applicable to those patients who have undergone adequate surgery. To better assess adequate lymph node yield from an MRM, a retrospective review was performed on 215 consecutive patients treated surgically for invasive breast cancer. Data from this review were compared with the surgical data from the above-mentioned radiotherapy trials. In a group of 131 patients who had MRM, the average number of nodes removed was 26 (median, 25), and 75.5% of the specimens had 20 or more lymph nodes. In 73 patients who underwent segmental mastectomy with axillary lymph node dissection, both the average and the median number of lymph nodes removed were 24, and 68.9% had 20 or more nodes. These data compare to the Danish radiation trial in which a median of 7 lymph nodes were removed (with 76% of the patients having 9 or fewer lymph nodes in the specimen) and to the Canadian radiation trial in which a median of 11 lymph nodes were removed. In addition, in our breast cancer patients with positive nodes (84 of 204; 41.2%), 45.2.% (38 of 84) had more than three positive nodes compared with 29.8% in the Danish study and 35% in the Canadian study. Our surgical data are sufficiently different from those of the Danish and Canadian studies to indicate that, in those studies, incomplete lymph node dissections were performed and that residual disease was left behind in the axilla in some or all of the patients. The addition of XRT in the setting of residual axillary disease may compensate for an inadequate operation and yield an acceptable oncological result; however, these studies did not provide an adequate comparison with a well-performed MRM without XRT. In the absence of documented benefit, XRT should not be routinely added if a complete lymph node dissection has been performed.

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

PubMed

Candido Dos Reis, Francisco J; Wishart, Gordon C; Dicks, Ed M; Greenberg, David; Rashbass, Jem; Schmidt, Marjanka K; van den Broek, Alexandra J; Ellis, Ian O; Green, Andrew; Rakha, Emad; Maishman, Tom; Eccles, Diana M; Pharoah, Paul D P

2017-05-22

PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40. The PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer.

Impact of intra-tumoral IL17A and IL32 gene expression on T-cell responses and lymph node status in breast cancer patients

PubMed Central

Bhat, Shreyas; Gardi, Nilesh; Hake, Sujata; Kotian, Nirupama; Sawant, Sharada; Kannan, Sadhana; Parmar, Vani; Desai, Sangeeta; Dutt, Amit

2018-01-01

Purpose Pro-inflammatory cytokines such as Interleukin-17A (IL17A) and Interleukin-32 (IL32), known to enhance natural killer and T cell responses, are also elevated in human malignancies and linked to poor clinical outcomes. To address this paradox, we evaluated relation between IL17A and IL32 expression and other inflammation- and T cell response-associated genes in breast tumors. Methods TaqMan-based gene expression analysis was carried out in seventy-eight breast tumors. The association between IL17A and IL32 transcript levels and T cell response genes, ER status as well as lymph node status was also examined in breast tumors from TCGA dataset. Results IL17A expression was detected in 32.7% ER-positive and 84.6% ER-negative tumors, with higher expression in the latter group (26.2 vs 7.1-fold, p < 0.01). ER-negative tumors also showed higher expression of IL32 as opposed to ER-positive tumors (8.7 vs 2.5-fold, p < 0.01). Expression of both IL17A and IL32 genes positively correlated with CCL5, GNLY, TBX21, IL21 and IL23 transcript levels (p < 0.01). Amongst ER-positive tumors, higher IL32 expression significantly correlated with lymph node metastases (p < 0.05). Conversely, in ER-negative subtype, high IL17A and IL32 expression was seen in patients with negative lymph node status (p < 0.05). Tumors with high IL32 and IL17A expression showed higher expression of TH1 response genes studied, an observation validated by similar analysis in the TCGA breast tumors (n=1041). Of note, these tumors were characterized by low expression of a potentially immunosuppressive isoform of IL32 (IL32γ). Conclusion These results suggest that high expression of both IL17A and IL32 leads to enhancement of T cell responses. Our study, thus, provides basis for the emergence of strong T cell responses in an inflammatory milieu that have been shown to be associated with better prognosis in ER-negative breast cancer. PMID:28470472

Selective sentinel lymph node biopsy in male breast cancer.

PubMed

Martin-Marcuartu, J J; Alvarez-Perez, R M; Sousa Vaquero, J M; Jimenez-Hoyuela García, J M

To evaluate the reproducibility of the sentinel lymph node (SLN) technique in male breast cancer. We retrospectively analysed 21 male patients diagnosed with breast cancer in our hospital from 2008 to 2016 with, at least, 18 months follow-up. Fifteen patients underwent selective sentinel lymph node biopsy (SLNB) following the usual protocols with peritumoral injection of 18.5-111MBq of 99m Tc-nanocoloides and acquisition of planar images 2hours after the injection. In 2 cases it was necessary to perform a SPECT/CT to locate the SLN. Immunohistochemistry and molecular techniques (OSNA) were used for their analysis. Six patients did not undergo SLNB because they had pathological nodes or distant disease at the time of diagnosis. SLNB was performed in 15 patients. The SLN was negative in 6 patients and positive in the remaining 9. Three patients with positive SLNB did not need axillary lymphadenectomy because of the low number of copies by molecular analysis OSNA. Axillary lymphadenectomy was performed in the remaining 6 patients with the result of 4 positive axillary lymphadenectomies and 2 that did not show further extension of the disease. According to our experience, SLNB in males is a reproducible, useful, safe and reliable technique which avoids unnecessary axillary lymphadenectomy and prevents the appearance of undesirable effects. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Correlation between hormone receptor status and age, and its prognostic implications in breast cancer patients in Bahrain

PubMed Central

AlZaman, Aysha S.; Mughal, Saad A.; AlZaman, Yahya S.; AlZaman, Entisar S.

2016-01-01

Objectives: To assess the correlation between hormone receptor status (HRS) and age, and its significance as a predictor of outcome in patients with breast cancer (BC). Methods: This retrospective review was conducted on 109 patients diagnosed with BC at Salmaniya Medical Complex, Manama, Bahrain from 2010-2013. Patients were divided into 2 age groups; under and over 40 years, and were analyzed for tumor histology, lymph node status, stage, and HRS. Results: Younger patients with BC were more likely to be of higher stage, grade, and of larger size. Older women were more likely to be estrogen receptor (ER) positive (72.6% versus 55.3%), and progesterone receptor (PR) positive (71% versus 53.2%) (p=0.03). The human epidermal growth factor receptor (HER)-2 over-expression was seen more in younger women (51% versus 40%) (p=0.2). Younger patients had higher lymph node metastases (88.6% versus 56.1%) (p=0.0004), and higher distant metastases (26.7% versus 6.8%) (p=0.005). The HER-2 over-expression strongly correlated with lymph node status. A total of 63.4% of lymph node positive patients had HER-2 over-expression compared with only 13.3% of lymph node negative patients (p<0.00001). Conclusion: Breast cancer is more aggressive and advanced in younger women, a fact that can be significantly attributed to under expression of ER and PR, and over expression of HER-2, which also correlates well with lymph node status, as a measure of aggressiveness. Further studies should evaluate the genetic profile of BC in such population to improve their outcomes. PMID:26739972

Clinical utility of routine pre-operative axillary ultrasound and fine needle aspiration cytology in patient selection for sentinel lymph node biopsy.

PubMed

Rattay, T; Muttalib, M; Khalifa, E; Duncan, A; Parker, S J

2012-04-01

In patients with operable breast cancer, pre-operative evaluation of the axilla may be of use in the selection of appropriate axillary surgery. Pre-operative axillary ultrasound (US) and fine needle aspiration cytology (FNAC) assessments have become routine practice in many breast units, although the evidence base is still gathering. This study assessed the clinical utility of US+/-FNAC in patient selection for either axillary node clearance (ANC) or sentinel lymph node biopsy (SLNB) in patients undergoing surgery for operable breast cancer. Over a two-year period, 348 patients with a clinically negative axilla underwent axillary US. 67 patients with suspicious nodes on US also underwent FNAC. The sensitivity and specificity of axillary investigations to determine nodal involvement were 56% (confidence interval: 47-64%) and 90% (84-93%) for US alone, and 76% (61-87%) and 100% (65-100%) for FNAC combined with US, respectively. With a positive US, the post-test probability was 78%. A negative US carried a post-test probability of 25%. When FNAC was positive, the post-test probability was greater than unity. A negative FNAC yielded a post-test probability of 52%. All patients with positive FNAC and most patients with suspicious US were listed for axillary node clearance (ANC) after consideration at the multi-disciplinary team (MDT) meeting. With pre-operative axillary US+/-FNAC, 20% of patients were saved a potential second axillary procedure, facilitating a reduction in the overall re-operation rate to 12%. In this study, a positive pre-operative US+/-FNAC directs patients towards ANC. When the result is negative, other clinico-pathological factors need to be taken into account in the selection of the appropriate axillary procedure. Copyright © 2011 Elsevier Ltd. All rights reserved.

Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women

PubMed Central

Patil, Vinayak W; Singhai, Rajeev; Patil, Amit V; Gurav, Prakash D

2011-01-01

The aim of our study was to analyze triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PgR), and the human epidermal growth factor receptor 2 (HER-2/neu) and which represents a subset of breast cancer with different biologic behavior. We investigated the clinicopathological characteristics and prognostic indicators of lymph node-negative TN breast cancer. Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India, from May 2007 to October 2010. Clinicopathological variables and clinical outcomes were evaluated. Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (<35 years, P = 0.003) and a higher histopathologic and nuclear grade (P < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for Bcl-2 expression (P < 0.001), positive for the epidermal growth factor receptor (P = 0.003), and a high level of p53 (P < 0.001) and Ki-67 expression (P < 0.00). The relapse rates during the follow-up period (median 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (P = 0.004). Relapse-free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer: 3.5-year RFS rate 85.5% versus 94.2%, respectively; P = 0.001. On multivariate analysis, young age, close resection margin, and triple negativity were independent predictors of shorter RFS. TN breast cancer had a higher relapse rate and more aggressive clinicopathological characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into risk factor analysis for node-negative breast cancer. PMID:24367172

Follow-Up Care for Older Women With Breast Cancer

DTIC Science & Technology

1998-08-01

and node status (positive/negative); and breast cancer treatments received. For the breast cancer treatments variables , we used two different ...interview. Independent Variables . We constructed five different measures of comorbidity. The first was a self-reported measure of cardiopulmonary...Candidate variables for our multivariate models included: baseline measures of the relevant outcome, age, stage, comorbidity, primary tumor therapy

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

PubMed

Furet, Elise; El Bouchtaoui, Morad; Feugeas, Jean-Paul; Miquel, Catherine; Leboeuf, Christophe; Beytout, Clémentine; Bertheau, Philippe; Le Rhun, Emilie; Bonneterre, Jacques; Janin, Anne; Bousquet, Guilhem

2017-06-06

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Handheld magnetic probe with permanent magnet and Hall sensor for identifying sentinel lymph nodes in breast cancer patients.

PubMed

Sekino, Masaki; Kuwahata, Akihiro; Ookubo, Tetsu; Shiozawa, Mikio; Ohashi, Kaichi; Kaneko, Miki; Saito, Itsuro; Inoue, Yusuke; Ohsaki, Hiroyuki; Takei, Hiroyuki; Kusakabe, Moriaki

2018-01-19

The newly developed radioisotope-free technique based on magnetic nanoparticle detection using a magnetic probe is a promising method for sentinel lymph node biopsy. In this study, a novel handheld magnetic probe with a permanent magnet and magnetic sensor is developed to detect the sentinel lymph nodes in breast cancer patients. An outstanding feature of the probe is the precise positioning of the sensor at the magnetic null point of the magnet, leading to highly sensitive measurements unaffected by the strong ambient magnetic fields of the magnet. Numerical and experimental results show that the longitudinal detection length is approximately 10 mm, for 140 μg of iron. Clinical tests were performed, for the first time, using magnetic and blue dye tracers-without radioisotopes-in breast cancer patients to demonstrate the performance of the probe. The nodes were identified through transcutaneous and ex-vivo measurements, and the iron accumulation in the nodes was quantitatively revealed. These results show that the handheld magnetic probe is useful in sentinel lymph node biopsy and that magnetic techniques are widely being accepted as future standard methods in medical institutions lacking nuclear medicine facilities.

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: Final results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouesse, Jacques; Lande, Brigitte de la; Bertheault-Cvitkovic, Frederique

Purpose: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. Methods and Materials: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m{sup 2} 5-fluorouracil, 12 mg/m{sup 2} mitoxantrone, and 500 mg/m{sup 2} cyclophosphamide, with concomitant radiotherapy (50 Gy {+-} 10-20-Gy boost). Patients in Arm B received 500 mg/m{sup 2} 5-fluorouracil, 60 mg/m{sup 2} epirubicin, and 500 mg/m{sup 2} cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. Results: Medianmore » treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). Conclusions: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.« less

[Breast cancer in México: a 10-year trend analysis on incidence and age at diagnosis].

PubMed

Salinas-Martínez, Ana María; Juárez-Ruiz, Abigail; Mathiew-Quirós, Álvaro; Guzmán-De la Garza, Francisco Javier; Santos-Lartigue, Adriana; Escobar-Moreno, César

2014-01-01

Breast cancer is an important public health problem. Some countries have achieved a downward trend while in others, continues ascending. In México, information on incidence and age at diagnosis is isolated in time, and knowledge on trend analysis is lacking. To examine the 2003-2012 trend of the incidence rate and age at diagnosis of breast cancer in the northeast of México. We also analyze the trend of positivity to nodes, hormone receptors and HER2; and its association with age at diagnosis. This is an epidemiological study of breast cancer patients in a tertiary care hospital in Monterrey, México (n = 3,488). Only new cases with a histology report were included; if this was not available, the cytology result was considered. Trend analysis was performed using the JoinPoint regression program Version 3.5. The breast cancer incidence rate increased from 26.7 to 49.8 per 100,000 between 2003 and 2011 (p < 0.05). The adjusted rate showed an annual percentage rate of change of +6.2% (95%CI 4.2, 8.2). The mean age was 55.7 ± 13.7 years and remained stable over time. Nodes, hormone receptors and HER2 positivity rate also remained stable over time. Age < 50 years increased twice the risk for positivity to nodes (OR 2.0, 95%CI 1.4, 2.7), ER-PR- (OR 1.8, 95% CI 1.4, 2.4) and ER-PR-HER2- (OR 1.9, 95%CI 1.5, 2.5). The 10-year analysis showed a significant upward trend. This study represents a first effort in our country, for determining patterns on incidence and age at diagnosis of breast cancer, as well as that of biomarkers.

Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67.

PubMed

Thangarajah, Fabinshy; Malter, Wolfram; Hamacher, Stefanie; Schmidt, Matthias; Krämer, Stefan; Mallmann, Peter; Kirn, Verena

2016-12-01

Since the introduction of the sentinel node technique for breast cancer in the 1990s patient's morbidity was reduced. Tracer uptake is known to be dependent from lymph node integrity and activity of macrophages. The aim of this study was to assess whether radioactivity of the tracer can predict sentinel lymph node metastases. Furthermore, a potential association with Ki-67 index was examined. Non-invasive prediction of lymph node metastases could lead to a further decrease of morbidity. We retrospectively analyzed patients with primary breast cancer who underwent surgery at the Department of Obstetrics and Gynecology in the University Hospital of Cologne between 2012 and 2013. Injection of radioactive tracer was done a day before surgery in the department of Nuclear Medicine. Clinical data and radioactivity of the sentinel node measured the day before and intraoperatively were abstracted from patient's files. Of 246 patients, 64 patients had at least one, five patients had two and one patient had three positive sentinel lymph nodes. Occurrence of sentinel lymph node metastases was not associated with preoperative tracer activity (p = 0,319), intraoperative tracer activity of first sentinel node (p = 0,086) or with loss of tracer activity until operation (p = 0,909). There was no correlation between preoperative Ki-67 index and occurrence of lymph node metastases (p = 0,403). In our cohort, there was no correlation between radioactivity and sentinel node metastases. Tracer uptake might not only be influenced by lymph node metastases and does not predict metastatic lymph node involvement. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Clinical Application of Mastectomy With Single Incision Followed by Immediate Laparoscopic-Assisted Breast Reconstruction With Latissimus Dorsi Muscle Flap.

PubMed

Yuan, Huozhong; Xie, Donghua; Xiao, Xigang; Huang, Xingwei

2017-08-01

To explore the clinical application of mastectomy with single incision followed by immediate laparoscopic-assisted breast reconstruction with latissimus dorsi muscle flap. Fifteen women with primary early breast cancer, 3 women with breast ductal carcinoma in situ, and 7 women with severe plasma cell mastitis were treated with partial mastectomy or total mastectomy, sentinel lymph node biopsy, or axillary lymph node dissection through a breast lateral transverse incision. Subsequent breast reconstruction with latissimus dorsi muscle flap was assisted by laparoscopy. The patient's position, time used in dissecting latissimus dorsi muscle flap, size of latissimus dorsi muscle flap, postoperative complications, and the cosmetic results after reconstruction were assessed. All the operations were well done through the breast lateral transverse incision and assistance of laparoscopy. The patient's position was changed only once during the operation. It took 1.5 to 2 hours to dissect latissimus dorsi muscle flap. The sizes of the latissimus dorsi muscle flap were 5 to 8 × 12 to 16 cm. There were no serious postoperative complications noted. The patients were satisfied with the appearance of the breasts and the small surgical scar. The surgical approach introduced is minimally invasive with concealed scar and outstanding cosmetic results. It is worth promoting in clinical application.

Adjuvant chemotherapy decisions in clinical practice for early-stage node-negative, estrogen receptor-positive, HER2-negative breast cancer: challenges and considerations.

PubMed

Nagaraj, Gayathri; Ma, Cynthia X

2013-03-01

Decisions regarding adjuvant chemotherapy for patients with estrogen receptor (ER)-positive, HER2-negative, lymph node-negative breast cancer have traditionally relied on clinical and pathologic parameters. However, the molecular heterogeneity and the complex tumor genome demand more sophisticated approaches to the problem. Several multigene-based assays have been developed to better prognosticate the risk of recurrence and death and predict benefit of therapy in this patient population. Oncologists are often faced with the challenge of incorporating these various complex genome-based biomarkers along with the traditional biomarkers in clinical decision-making. The NCCN Clinical Practice Guidelines in Oncology for Breast Cancer are helpful in providing a general recommendation. However, uncertainty remains in the absence of definitive data for various clinical scenarios. This case report describes a postmenopausal woman with stage I breast cancer that is low-grade and ER-rich, and has an intermediate Oncotype DX recurrence score of 28.

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

PubMed

Paik, Soonmyung; Tang, Gong; Shak, Steven; Kim, Chungyeul; Baker, Joffre; Kim, Wanseop; Cronin, Maureen; Baehner, Frederick L; Watson, Drew; Bryant, John; Costantino, Joseph P; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2006-08-10

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Integrating Comparative Effectiveness Design Elements and Endpoints Into a Phase III, Randomized Clinical Trial (SWOG S1007) Evaluating OncotypeDX-Guided Management for Women With Breast Cancer Involving Lymph Nodes

PubMed Central

Ramsey, Scott D.; Barlow, William E.; Gonzalez-Angulo, Ana M.; Tunis, Sean; Baker, Laurence; Crowley, John; Deverka, Patricia; Veenstra, David; Hortobagyi, Gabriel N.

2012-01-01

Women with breast cancer involving the lymph nodes are typically treated with cytotoxic chemotherapy. Retrospective evaluations of prior studies suggest that the 21-gene test (OncotypeDX®), may allow identification of those who can safely avoid chemotherapy. To better understand the performance of the 21-gene test, the RxPONDER (Rx for Positive Node, Endocrine Responsive breast cancer) study was designed, a multicenter Phase III trial randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1–3 lymph nodes and a 21-gene assay recurrence score (RS) of 25 or less to endocrine therapy alone versus chemotherapy followed by endocrine therapy. As one of the first large-scale comparative-effectiveness studies in oncology, RxPONDER utilized an external stakeholder group to help inform the design of the trial. Stakeholders met with representatives of SWOG over several months through a structured discussion process. The stakeholder engagement process resulted in several changes being made to the trial design. In addition, stakeholder representatives from the health insurance industry provided guidance regarding a mechanism whereby the costs of OncotypeDX® would be paid by the majority of health insurers as part of the trial. The process may serve as a template for future studies evaluating the comparative effectiveness of genomic tests in oncology, particularly those that are conducted within cooperative clinical trials groups. PMID:23000081

Application of neoadjuvant chemotherapy in occult breast cancer

PubMed Central

Yang, Haisong; Li, Ling; Zhang, Mengmeng; Zhang, Shiyong; Xu, Shu; Ma, Xiaoxia

2017-01-01

Abstract Rationale: Although rare, occult breast cancer (OBC) originates from breast tissue. Its primary lesions cannot be identified by clinical examination or imaging; therefore, the diagnosis, treatment, and prognosis remain controversial. Patient concerns: This study comprised 5 female OBC patients who were admitted to the Affiliated Hospital of Guizhou Medical University for painless axillary lumps. Diagnoses: 18F-flurodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) indicated metastasis in the ipsilateral axillary lymph nodes. No clear breast primary lesions were identified; other organs were also excluded as the primary site. Pathological biopsy confirmed axillary lymph node metastasis of adenocarcinoma. Immunohistochemical staining of the tumor to identify the source revealed that estrogen receptors (ERs) and progesterone receptors (PgRs) were positive in 2 cases, ER was positive and PR was negative in 1 case, and both were negative in 2 cases. Human epidermal growth factor receptor 2 was negative in all cases. All patients were diagnosed with OBC. Interventions: All patients underwent neoadjuvant chemotherapy (NAC). One patient did not undergo follow-up therapy. The other 4 underwent total mastectomy plus axillary lymph node dissection followed by radiotherapy. Two patients also underwent endocrine therapy. Outcomes: Patients were followed up for 9.0 to 72.0 months. Four achieved pathological complete response. One patient experienced metastasis to the ipsilateral supraclavicular lymph nodes 2.0 years later, which was cleared after additional treatment. The other patients were tumor free. Lessons: Here, we are reporting 5 cases of OBC treated with NAC that were evaluated by 18F-FDG PET/CT scans. This study suggests that NAC might lead to a positive outcome. PMID:28984771

Validity of St Gallen risk categories in prognostication of breast cancer patients in Southern Sri Lanka.

PubMed

Peiris, Harshini; Mudduwa, Lakmini; Thalagala, Neil; Jayatilake, Kamani

2018-01-31

Although, there are many developments in the field of management, breast cancer is still the commonest cause of cancer related deaths in women in Sri Lanka. This emphasizes the need for validation of treatment protocols that are used in Sri Lanka for managing breast cancers. There are no published papers on treatment and survival of breast cancer patients in Sri Lanka. Hence this study was designed to determine the validity of St Gallen risk categories based on the survival outcomes of breast cancer patients in Southern Sri Lanka. This retro-prospective study included all female breast cancer patients who had sought the immunohistochemistry services of our unit from May 2006 to December 2012. Patients who had neo-adjuvant chemotherapy were excluded. Patients were stratified according to the St Gallen risk categories; low-risk (LR), intermediate-risk (IR) and high-risk (HR), which is used in deciding on the adjuvant treatment. IR category was subdivided based on presence/absence of 1-3 positive-nodes (absent-IR1, present-IR2) and HR on the number of positive-nodes(1-3 lymph nodes;HR1,> 3 lymph nodes;HR2). Kaplan-Meier and Cox-regression models were used in the survival analysis. This study included 713breast cancer patients (LR-2%, IR1-45%, IR2-10%, HR1-13%, HR2-30%). Five year breast cancer specific survival (BCSS)wasLR-100%, IR-91%, HR-66% and the recurrence free survival (RFS) was LR-85%, IR-84%, HR-65%. BCSS and RFS curves were significantly different between the three risk categories (p < 0.001). No survival difference was evident between the IR1 and IR2 (BCSS-p = 0.232, RFS-p = 0.118). HR1 and HR2 had a distinctly different BCSS (p = 0.033) with no difference in RFS (p = 0.190). This study validates the St Gallen risk categorization of female breast cancer patients in our setting. However, the HR includes two subsets of patients with a distinct difference in BCSS.

Prognostic Significance of the Number of Positive Lymph Nodes in Women With T1-2N1 Breast Cancer Treated With Mastectomy: Should Patients With 1, 2, and 3 Positive Lymph Nodes Be Grouped Together?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai Kubicky, Charlotte, E-mail: charlottedai@gmail.com; Mongoue-Tchokote, Solange

2013-04-01

Purpose: To determine whether patients with 1, 2, or 3 positive lymph nodes (LNs) have similar survival outcomes. Methods and Materials: We analyzed the Surveillance, Epidemiology, and End Results registry of breast cancer patients diagnosed between 1990 and 2003. We identified 10,415 women with T1-2N1M0 breast cancer who were treated with mastectomy with no adjuvant radiation, with at least 10 LNs examined and 6 months of follow-up. The Kaplan-Meier method and log–rank test were used for survival analysis. Multivariate analysis was performed using the Cox proportional hazard model. Results: Median follow-up was 92 months. Ten-year overall survival (OS) and cause-specificmore » survival (CSS) were progressively worse with increasing number of positive LNs. Survival rates were 70%, 64%, and 60% (OS), and 82%, 76%, and 72% (CSS) for 1, 2, and 3 positive LNs, respectively. Pairwise log–rank test P values were <.001 (1 vs 2 positive LNs), <.001 (1 vs 3 positive LNs), and .002 (2 vs 3 positive LNs). Multivariate analysis showed that number of positive LNs was a significant predictor of OS and CSS. Hazard ratios increased with the number of positive LNs. In addition, age, primary tumor size, grade, estrogen receptor and progesterone receptor status, race, and year of diagnosis were significant prognostic factors. Conclusions: Our study suggests that patients with 1, 2, and 3 positive LNs have distinct survival outcomes, with increasing number of positive LNs associated with worse OS and CSS. The conventional grouping of 1-3 positive LNs needs to be reconsidered.« less

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells.

PubMed

Workman, Heather C; Miller, Jamie K; Ingalla, Ellen Q; Kaur, Rouminder P; Yamamoto, Diane I; Beckett, Laurel A; Young, Lawrence Jt; Cardiff, Robert D; Borowsky, Alexander D; Carraway, Kermit L; Sweeney, Colleen; Carraway, Kermit L

2009-01-01

Previous studies indicate that overexpression of the membrane-associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and suppresses cellular apoptotic response to a variety of insults. Such observations raise the possibility that MUC4 expression could contribute to tumor progression or metastasis, but the potential involvement of MUC4 in breast cancer has not been rigorously assessed. The present study aimed to investigate the expression of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and lymph node metastases, and to evaluate the role of MUC4 in promoting the malignant properties of breast tumor cells. MUC4 expression levels in patient-matched normal and tumor breast tissue was initially examined by immunoblotting lysates of fresh frozen tissue samples with a highly specific preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis was then carried out using tissue microarrays encompassing patient-matched normal breast tissue and primary tumors, and patient-matched lymph node metastases and primary tumors. Finally, shRNA-mediated knockdown was employed to assess the contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1 breast cancer cells. Immunoblotting and immunohistochemistry revealed that MUC4 levels are suppressed in the majority (58%, p < 0.001) of primary tumors relative to patient-matched normal tissue. On the other hand, lymph node metastatic lesions from 37% (p < 0.05) of patients expressed higher MUC4 protein levels than patient-matched primary tumors. MUC4-positive tumor emboli were often found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated MUC4 knockdown compromised the migration, proliferation and anoikis resistance of JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to cellular properties associated with breast tumor metastasis. Our observations suggest that after an initial loss of MUC4 levels during the transition of normal breast tissue to primary tumor, the re-establishment of elevated MUC4 levels confers an advantage to metastasizing breast tumor cells by promoting the acquisition of cellular properties associated with malignancy.

Evaluation of Breast Sentinel Lymph Node Coverage by Standard Radiation Therapy Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabinovitch, Rachel; Ballonoff, Ari; Newman, Francis M.S.

2008-04-01

Background: Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described. Methods and Materials: A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standardmore » axillary fields in 106 data sets meeting these criteria. Results: The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%. Conclusions: Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.« less

Contribution of Kinetic Characteristics of Axillary Lymph Nodes to the Diagnosis in Breast Magnetic Resonance Imaging

PubMed Central

Örgüç, Şebnem; Başara, Işıl; Pekindil, Gökhan; Coşkun, Teoman

2012-01-01

Objective: To assess the contribution of kinetic characteristics in the discrimination of malignant-benign axillary lymph nodes. Material and Methods: One hundred fifty-five female patients were included in the study. Following magnetic resonance imaging (MRI) examinations postprocessing applications were applied, dynamic curves were obtained from subtracted images. Types of dynamic curves were correlated with histopathological results in malignant cases or final clinical results in patients with no evidence of malignancy. Sensitivity, specificity, positive likehood ratio (+LHR), negative (−LHR) of dynamic curves characterizing the axillary lymph nodes were calculated. Results: A total of 178 lymph nodes greater than 8 mm were evaluated in 113 patients. Forty-six lymph nodes in 24 cases had malignant axillary involvement. 132 lymph nodes in 89 patients with benign diagnosis were included in the study. The sensitivity of type 3 curve as an indicator of malignancy was calculated as 89%. However the specificity, +LHR, −LHR were calculated as 14%, 1.04, 0.76 respectively. Conclusion: Since kinetic analysis of both benign and malignant axillary lymph nodes, rapid enhancement and washout (type 3) they cannot be used as a discriminator, unlike breast lesions. MRI, depending on the kinetic features of the axillary lymph nodes, is not high enough to be used in the clinical management of breast cancer patients. PMID:25207016

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

PubMed

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N; Dean, Michelle; Lees-Miller, Susan P; Riabowol, Karl; Magliocco, Anthony M; Morris, Don; Watson, Peter H; Enwere, Emeka K; Bebb, Gwyn; Paterson, Alexander

2016-12-27

This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer

PubMed Central

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N.; Dean, Michelle; Lees-Miller, Susan P.; Riabowol, Karl; Magliocco, Anthony M.; Morris, Don; Watson, Peter H.; Enwere, Emeka K.; Bebb, Gwyn; Paterson, Alexander

2016-01-01

Introduction This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. Methods 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Results Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). Conclusions These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC. PMID:27741524

Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doyen, J.; Trastour, C.; Ettore, F.

2014-08-15

Highlights: • Glycolytic markers are highly expressed in triple negative breast cancers. • Lactate/H{sup +} symporter MCT4 demonstrated the strongest deleterious impact on survival. • MCT4 should serve as a new prognostic factor in node-negative breast cancers. - Abstract: Background: {sup 18}Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohortsmore » of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H{sup +} symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.« less

Locoregional Recurrence Risk for Patients With T1,2 Breast Cancer With 1-3 Positive Lymph Nodes Treated With Mastectomy and Systemic Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

McBride, Andrew; University of Arizona School of Medicine, Phoenix, Arizona; Allen, Pamela

2014-06-01

Purpose: Postmastectomy radiation therapy (PMRT) has been shown to benefit breast cancer patients with 1 to 3 positive lymph nodes, but it is unclear how modern changes in management have affected the benefits of PMRT. Methods and Materials: We retrospectively analyzed the locoregional recurrence (LRR) rates in 1027 patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with mastectomy and adjuvant chemotherapy with or without PMRT during an early era (1978-1997) and a later era (2000-2007). These eras were selected because they represented periods before and after the routine use of sentinel lymph node surgery, taxanemore » chemotherapy, and aromatase inhibitors. Results: 19% of 505 patients treated in the early era and 25% of the 522 patients in the later era received PMRT. Patients who received PMRT had significantly higher-risk disease features. PMRT reduced the rate of LRR in the early era cohort, with 5-year rates of 9.5% without PMRT and 3.4% with PMRT (log-rank P=.028) and 15-year rates 14.5% versus 6.1%, respectively; (Cox regression analysis: adjusted hazard ratio [AHR] 0.37, P=.035). However, PMRT did not appear to benefit patients treated in the later cohort, with 5-year LRR rates of 2.8% without PMRT and 4.2% with PMRT (P=.48; Cox analysis: AHR 1.41, P=.48). The most significant factor predictive of LRR for the patients who did not receive PMRT was the era in which the patient was treated (AHR 0.35 for later era, P<.001). Conclusion: The risk of LRR for patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with mastectomy and systemic treatment is highly dependent on the era of treatment. Modern treatment advances and the selected use of PMRT for those with high-risk features have allowed for identification of a cohort at very low risk for LRR without PMRT.« less

Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study

PubMed Central

Petkov, Valentina I; Miller, Dave P; Howlader, Nadia; Gliner, Nathan; Howe, Will; Schussler, Nicola; Cronin, Kathleen; Baehner, Frederick L; Cress, Rosemary; Deapen, Dennis; Glaser, Sally L; Hernandez, Brenda Y; Lynch, Charles F; Mueller, Lloyd; Schwartz, Ann G; Schwartz, Stephen M; Stroup, Antoinette; Sweeney, Carol; Tucker, Thomas C; Ward, Kevin C; Wiggins, Charles; Wu, Xiao-Cheng; Penberthy, Lynne; Shak, Steven

2016-01-01

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40–84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results (N=38,568). Unadjusted 5-year BCSM were 0.4% (n=21,023; 95% confidence interval (CI), 0.3–0.6%), 1.4% (n=14,494; 95% CI, 1.1–1.7%), and 4.4% (n=3,051; 95% CI, 3.4–5.6%) for Recurrence Score <18, 18–30, and ⩾31 groups, respectively (P<0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM (P<0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N=4,691), 5-year BCSM (unadjusted) was 1.0% (n=2,694; 95% CI, 0.5–2.0%), 2.3% (n=1,669; 95% CI, 1.3–4.1%), and 14.3% (n=328; 95% CI, 8.4–23.8%) for Recurrence Score <18, 18–30, ⩾31 groups, respectively (P<0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials. PMID:28721379

Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients.

PubMed

Bonin, Serena; Parascandolo, Alessia; Aversa, Cinzia; Barbazza, Renzo; Tsuchida, Nobuo; Castellone, Maria Domenica; Stanta, Giorgio; Vecchio, Giancarlo

2018-03-16

The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases. Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness. This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival. We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.

Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes.

PubMed

Cobleigh, Melody A; Tabesh, Bita; Bitterman, Pincas; Baker, Joffre; Cronin, Maureen; Liu, Mei-Lan; Borchik, Russell; Mosquera, Juan-Miguel; Walker, Michael G; Shak, Steven

2005-12-15

This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer patients. Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.

Intraductal papilloma in an axillary lymph node of a patient with human immunodeficiency virus: a case report and review of the literature.

PubMed

Cottom, Hannah; Rengabashyam, Bhavani; Turton, Philip E; Shaaban, Abeer M

2014-05-23

Inclusions of ectopic breast tissue in axillary lymph nodes are reported very infrequently and typically are only identified microscopically as an incidental finding. Furthermore the development of a benign proliferative lesion in the form of an intraductal papilloma from intranodal ectopic breast tissue is an extremely rare phenomenon with only three previous cases reported. This report describes an unusual and rare case of an intraductal papilloma arising in an axillary lymph node of a patient known to have the human immunodeficiency virus. A 40-year-old Black African woman underwent excision of an enlarged palpable axillary lymph node. In the preceding 7 years she had received at least six separate surgical excisions to her ipsilateral breast for papillomatosis. The last surgical intervention was performed 1 year prior to presentation with an enlarged axillary lymph node. Histological examination of her axillary lymph node revealed a papillomatous proliferative epithelial lesion within an apparent encompassing duct, resembling a mammary intraductal papilloma. In the surrounding lymphoid tissue small groups of duct-like structures were additionally noted. Immunostaining with a panel of myoepithelial markers in conjunction with oestrogen receptor produced a mixed heterogeneous staining pattern in both the papillomatous lesion and the peripheral duct-like structures. This confirmed the diagnosis of a benign intraductal papilloma within an axillary lymph node, considered to have arisen from ectopic breast tissue. This case demonstrates that intranodal ectopic breast tissue has the potential to undergo benign proliferative change albeit extremely rarely. Therefore this possibility must be considered to ensure the correct diagnosis is made. In addition, to the best of our knowledge, this is the first case report which has described recurrent intraductal papillomas and the subsequent development of an intraductal papilloma within an ipsilateral axillary lymph node, in a patient who is human immunodeficiency virus positive. There is minimal literature investigating the specific types of breast pathologies experienced by patients infected with human immunodeficiency virus and it remains unexplored as to whether human immunodeficiency virus may lead to proliferative papillomatous epithelial changes. This report considers the role of the human papillomavirus and recommends that further investigatory studies are required.

The value of detection of S100A8 and ASAH1 in predicting the chemotherapy response for breast cancer patients.

PubMed

Li, Yu-Hong; Liu, Hai-Ting; Xu, Jing; Xing, Ai-Yan; Zhang, Jie; Wang, Ya-Wen; Yin, Gang; Gao, Peng

2018-04-01

Chemotherapy plays an important role in the treatment of breast cancer. However, chemoresistance remains the main obstacle for effective treatment, leading to poor prognosis. This study aims to investigate the value of detection of S100A8 and ASAH1 in predicting the chemotherapy response. Miller and Payne grades were used to assess the chemotherapy response in breast cancers. The expression of S100A8 and ASAH1, as well as ER, PR, HER2 and Ki-67 were assessed by immunohistochemical staining in 120 cases of non-special type invasive ductal carcinoma (IDC-NOS). S100A8 expression was higher in chemosensitive breast cancers than chemoresistant ones. Moreover, S100A8 expression was significantly correlated with the molecular subtypes and histological grade, but not with patients' age, tumor size and lymph nodes status. However, there was no significant difference in ASAH1 expression between chemoresistant and chemosensitive group. We also found that higher ASAH1 expression was correlated with positive lymph nodes status, but not with age, tumor size, molecular subtypes and histological grade. S100A8 was valuable in predicting chemotherapy response in breast cancers. The expression of ASAH1 was associated significantly with lymph nodes metastasis, indicating that ASAH1 may serve as a biomarker to predict patients' lymph nodes status in breast cancers. Copyright © 2018 Elsevier Inc. All rights reserved.

SU-E-T-292: Dosimetric Advantage of Prone Breast Radiotherapy for Korean Left-Sided Breast Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Y; Shin, J; Yu, J

Purpose: To evaluate the dosimetric benefit of prone breast radiotherapy for Korean left-sided early-stage breast cancer patients who have relatively small breast Methods: From April to June, 2014, 10 left-sided breast cancer patients received the whole breast irradiation in prone position after partial mastectomy with sentinel lymph node biopsy or axillary lymph node dissection. All patients were pTmi-2N0-1mi. Each patient underwent two computed tomoradiography (CT) simulations in supine and prone positions. The whole breast, ipsilateral lung, heart, and left anterior descending coronary artery (LAD) were contoured on each simulation CT images, and then tangential-fields treatment plan in each position wasmore » designed for the whole breast irradiation with the total dose of 50 Gy in 2 Gy fractions. Dose-volume histograms of two setups were compared for target coverage and radiation dose to normal organs with Wilcoxon signed rank tests. Results: The median age of patients was 47 years (range, 37 to 53). The median chest size was 82.5 cm (range, 75 to 90) and bra cup size was A in 4, B in 4, and C in 2 patients. The radiation dose to the whole breast was similar when comparing mean dose (Dmean) and dose covering 95% of the breast volume, but maximum dose (Dmax) of breast was higher in supine (median 52.3 vs. 52.7 Gy, p=0.013). Prone position reduced significantly the radiation dose in ipsilateral lung, heart, and LAD by median 5.7, 1.1, and 6.9 Gy of Dmean (p=0.005, 0.007, and 0.005) and 28.2, 18.8, and 35.0 Gy of Dmax (p=0.005, 0.005, and 0.007), respectively. Conclusion: Prone breast radiotherapy could be beneficial for Korean breast cancer patients since it substantially spared normal organs while achieving adequate coverage of the breast tissue. Further prospective study is required to validate the potential benefit of prone breast radiotherapy.« less

Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients.

PubMed

Mosalpuria, Kailash; Hall, Carolyn; Krishnamurthy, Savitri; Lodhi, Ashutosh; Hallman, D Michael; Baraniuk, Mary S; Bhattacharyya, Anirban; Lucci, Anthony

2014-09-01

Triple-negative breast cancer (TNBC) is characterised by lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)2/neu gene amplification. TNBC patients typically present at a younger age, with a larger average tumor size, higher grade and higher rates of lymph node positivity compared to patients with ER/PR-positive tumors. Cyclooxygenase (COX)-2 regulates the production of prostaglandins and is overexpressed in a variety of solid tumors. In breast cancer, the overexpression of COX-2 is associated with indicators of poor prognosis, such as lymph node metastasis, poor differentiation and large tumor size. Since both TNBC status and COX-2 overexpression are known poor prognostic markers in primary breast cancer, we hypothesized that the COX-2 protein is overexpressed in the primary tumors of TNBC patients. The purpose of this study was to determine whether there exists an association between TNBC status and COX-2 protein overexpression in primary breast cancer. We prospectively evaluated COX-2 expression levels in primary tumor samples obtained from 125 patients with stage I-III breast cancer treated between February, 2005 and October, 2007. Information on clinicopathological factors was obtained from a prospective database. Baseline tumor characteristics and patient demographics were compared between TNBC and non-TNBC patients using the Chi-square and Fisher's exact tests. In total, 60.8% of the patients were classified as having ER-positive tumors, 51.2% were PR-positive, 14.4% had HER-2/neu amplification and 28.0% were classified as TNBC. COX-2 overexpression was found in 33.0% of the patients. TNBC was associated with COX-2 overexpression (P=0.009), PR expression (P=0.048) and high tumor grade (P=0.001). After adjusting for age, menopausal status, body mass index (BMI), lymph node status and neoadjuvant chemotherapy (NACT), TNBC was an independent predictor of COX-2 overexpression (P=0.01). In conclusion, the association between TNBC and COX-2 overexpression in operable breast cancer supports further investigation into COX-2-targeted therapy for patients with TNBC.

Impact of smoking history on the outcomes of women with early-stage breast cancer: a secondary analysis of a randomized study.

PubMed

Abdel-Rahman, Omar; Cheung, Winson Y

2018-04-11

To assess the impact of smoking history on the outcomes of early-stage breast cancer patients treated with sequential anthracyclines-taxanes in a randomized study. This is a secondary analysis of patient-level data of 1242 breast cancer patients referred for adjuvant chemotherapy in the BCIRG005 clinical trial. Overall survival was assessed according to smoking history through Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses of factors affecting overall and relapse-free survival were subsequently conducted. Factors that were evaluated included: age, performance status, number of chemotherapy cycles, T stage, lymph node ratio, estrogen receptor status, adjuvant radiotherapy and smoking history. Kaplan-Meier analysis of overall survival according to smoking status (ever smoker vs. never smoker) was conducted. There was a trend toward a better overall survival among never smokers compared to ever smokers; however, it was not statistically significant (P = 0.098). The following factors were associated with better overall survival in multivariate analysis: older age (P = 0.011), complete chemotherapy course (P = 0.002), lower T stage (P < 0.0001), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P = 0.006). Otherwise, the following factors were associated with better relapse-free survival in multivariate analysis: older age (P = 0.001), never smoking status (P = 0.021), lower T stage (P = 0.028), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P < 0.0001). Early-stage breast cancer patients with a positive smoking history experienced worse relapse-free survival compared to never smokers. Physicians managing breast cancer patients should prioritize discussion about the benefits of smoking cessation when counseling their patients.

Assessment of Risk Factors in Patients who presented to the Outpatient Clinic for Breast Cancer-Related Lymphedema

PubMed Central

Can, Aslı Gençay; Ekşioğlu, Emel; Bahtiyarca, Zeynep Tuba; Çakcı, Fatma Aytül

2016-01-01

Objective Lymphedema is one of the most debilitating outcomes of breast cancer treatment. We aimed to compare the demographic and clinical characteristics of breast cancer patients with and without lymphedema, to assess risk factors for lymphedema, and to evaluate treatment outcomes in lymphedema patients. Materials and Methods Demographic and clinical characteristics of 84 women with previous surgery for breast cancer who presented to the outpatient clinic between March 2014 and May 2015 were retrospectively extracted from patient records. Results Upper extremity lymphedema was detected in 34 of 84 patients (40.5%). The mean age, body mass index, the number of positive lymph nodes and the number of patients with postoperative radiotherapy were significantly higher among patients with lymphedema than those without (p<0.05). Educational level of patients with lymphedema was significantly lower than the other group (p<0.05). The correlation analysis revealed an association between age, educational level, body mass index, tumor stage, number of positive lymph nodes, postoperative radiotherapy and presence of lymphedema. Postoperative radiotherapy was detected as the only independent risk factor by logistic regression analysis. Fourteen out of 26 lymphedema patients were assigned to education, skin care, exercise and compression bandaging therapy. Upper extremity volumes and volume differences were significantly improved after treatment. Conclusion Advanced age, low educational level, obesity, tumor size, the number of positive lymph nodes and postoperative radiotherapy correlated with the development of lymphedema. Within these factors, postoperative radiotherapy was detected as an independent risk factor for the development of lymphedema. Patient education, skin care, exercise and compression bandage therapy are effective treatment options in breast cancer-related lymphedema. PMID:28331728

Plasma MMP1 and MMP8 expression in breast cancer: Protective role of MMP8 against lymph node metastasis

PubMed Central

Decock, Julie; Hendrickx, Wouter; Vanleeuw, Ulla; Van Belle, Vanya; Van Huffel, Sabine; Christiaens, Marie-Rose; Ye, Shu; Paridaens, Robert

2008-01-01

Background Elevated levels of matrix metalloproteinases have been found to associate with poor prognosis in various carcinomas. This study aimed at evaluating plasma levels of MMP1, MMP8 and MMP13 as diagnostic and prognostic markers of breast cancer. Methods A total of 208 breast cancer patients, of which 21 with inflammatory breast cancer, and 42 healthy controls were included. Plasma MMP1, MMP8 and MMP13 levels were measured using ELISA and correlated with clinicopathological characteristics. Results Median plasma MMP1 levels were higher in controls than in breast cancer patients (3.45 vs. 2.01 ng/ml), while no difference was found for MMP8 (10.74 vs. 10.49 ng/ml). ROC analysis for MMP1 revealed an AUC of 0.67, sensitivity of 80% and specificity of 24% at a cut-off value of 4.24 ng/ml. Plasma MMP13 expression could not be detected. No correlation was found between MMP1 and MMP8 levels. We found a trend of lower MMP1 levels with increasing tumour size (p = 0.07); and higher MMP8 levels with premenopausal status (p = 0.06) and NPI (p = 0.04). The median plasma MMP1 (p = 0.02) and MMP8 (p = 0.007) levels in the non-inflammatory breast cancer patients were almost twice as high as those found in the inflammatory breast cancer patients. Intriguingly, plasma MMP8 levels were positively associated with lymph node involvement but showed a negative correlation with the risk of distant metastasis. Both controls and lymph node negative patients (pN0) had lower MMP8 levels than patients with moderate lymph node involvement (pN1, pN2) (p = 0.001); and showed a trend for higher MMP8 levels compared to patients with extensive lymph node involvement (pN3) and a strong predisposition to distant metastasis (p = 0.11). Based on the hypothesis that blood and tissue protein levels are in reverse association, these results suggest that MMP8 in the tumour may have a protective effect against lymph node metastasis. Conclusion In summary, we observed differences in MMP1 and MMP8 plasma levels between healthy controls and breast cancer patients as well as between breast cancer patients. Interestingly, our results suggest that MMP8 may affect the metastatic behaviour of breast cancer cells through protection against lymph node metastasis, underlining the importance of anti-target identification in drug development. PMID:18366705

Intraoperative analysis of sentinel lymph nodes by imprint cytology for cancer of the breast.

PubMed

Shiver, Stephen A; Creager, Andrew J; Geisinger, Kim; Perrier, Nancy D; Shen, Perry; Levine, Edward A

2002-11-01

The utilization of lymphatic mapping techniques for breast carcinoma has made intraoperative evaluation of sentinel lymph nodes (SLN) attractive, because axillary lymph node dissection can be performed during the initial surgery if the SLN is positive. The optimal technique for rapid SLN assessment has not been determined. Both frozen sectioning and imprint cytology are used for rapid intraoperative SLN evaluation. A retrospective review of the intraoperative imprint cytology results of 133 SLN mapping procedures from 132 breast carcinoma patients was performed. SLN were evaluated intraoperatively by bisecting the lymph node and making imprints of each cut surface. Imprints were stained with hematoxylin and eosin (H&E) and Diff-Quik. Permanent sections were evaluated with up to four H&E stained levels and cytokeratin immunohistochemistry. Imprint cytology results were compared with final histologic results. Sensitivity and specificity of imprint cytology were 56% and 100%, respectively, producing a 100% positive predictive value and 88% negative predictive value. Imprint cytology was significantly more sensitive for macrometastasis than micrometastasis 87% versus 22% (P = 0.00007). Of 13 total false negatives, 11 were found to be due to sampling error and 2 due to errors in intraoperative interpretation. Both intraoperative interpretation errors involved a diagnosis of lobular breast carcinoma. The sensitivity and specificity of imprint cytology are similar to that of frozen section evaluation. Imprint cytology is therefore a viable alternative to frozen sectioning when intraoperative evaluation is required. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

PubMed

Brouwer, O R; Vermeeren, L; van der Ploeg, I M C; Valdés Olmos, R A; Loo, C E; Pereira-Bouda, L M; Smit, F; Neijenhuis, P; Vrouenraets, B C; Sivro-Prndelj, F; Jap-a-Joe, S M; Borgstein, P J; Rutgers, E J Th; Oldenburg, H S A

2012-07-01

To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or multifocal breast cancer.

Repeat sentinel lymph node biopsy in patients with ipsilateral recurrent breast cancer after breast-conserving therapy and negative sentinel lymph node biopsy: a prospective study.

PubMed

Folli, Secondo; Falco, Giuseppe; Mingozzi, Matteo; Buggi, Federico; Curcio, Annalisa; Ferrari, Guglielmo; Taffurelli, Mario; Regolo, Lea; Nanni, Oriana

2016-04-01

Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery with negative sentinel lymph node biopsy need a new axillary staging procedure. However, the best surgical option, i.e. repeat sentinel lymph node biopsy or axillary lymph node dissection, is still debated. Purpose of the study is to assess the performance of repeat sentinel lymph node biopsy. In a multicenter study, lymph node biopsy completed by back-up axillary lymph node dissection was undertaken for ipsilateral breast tumor recurrence or new ipsilateral primary tumor. Tracer uptake was used to identify and isolate the sentinel lymph node during surgery, and it was classified after staining with hematoxylin and eosin and monoclonal anti-cytokeratin antibodies. Aside from negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. A multicenter, prospective study was conducted performing 30 repeat sentinel lymph node biopsy completed by back-up axillary lymph node dissection for ipsilateral breast tumor recurrence or new ipsilateral primary tumor in patients formerly treated with previous breast conservative surgery and negative sentinel lymph node biopsy. Negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. Sentinel lymph nodes were mapped in 27 patients out of 30 (90%). Aberrant drainage pathways were observed in one patient (3.7%). Tracer uptake was sufficient to identify and isolate the sentinel lymph node during surgery in 23 cases (76.6%); the patients in whom lymphoscintigraphy failed or no sentinel lymph nodes could be isolated underwent axillary lymph node dissection. The negative predictive value was 95.2%, the accuracy was 95.6% and the false-negative rate was 33%. Repeat sentinel lymph node biopsy is feasible and accurate, with a high negative predictive value. Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery and negative sentinel lymph node biopsy can be treated with repeat sentinel lymph node biopsy for the axillary staging and can be spared axillary dissection in case of absence of metastases. However, repeat sentinel lymph node biopsy may prove technically impracticable in about one quarter of cases and thus axillary lymph node dissection remains the only viable option in such instance.

A simplified CT-based definition of the supraclavicular and infraclavicular nodal volumes in breast cancer.

PubMed

Atean, I; Pointreau, Y; Ouldamer, L; Monghal, C; Bougnoux, A; Bera, G; Barillot, I

2013-02-01

The available contouring guidelines for the supraclavicular and infraclavicular lymph nodes appeared to be inadequate for their delineation on non-enhanced computed tomography (CT) scans. For this purpose, we developed delineation guidelines for the clinical target volumes (CTV) of these lymph nodes on non-enhanced CT-slices performed in the treatment position of breast cancer. A fresh female cadaver study as well as delineation and an anatomical descriptions review were performed to propose a simplified definition of the supra- and infraclavicular lymph nodes using readily identifiable anatomical structures. This definition was developed jointly by breast radiologists, breast surgeons, and radiation oncologists. To validate these guidelines, the primary investigator and seven radiation oncologists (observers) independently delineated 10 different nodal CTVs. The primary investigator contours were considered to be the gold standard contours. Contour accuracy and concordance were evaluated. Written guidelines for the delineation of supra- and infraclavicular lymph nodes CTVs were developed. Consistent contours with minimal variability existed between the delineated volumes; the mean kappa index was 0.83. The mean common contoured and additional contoured volumes were 84.6% and 18.5%, respectively. The mean overlap volume ratio was 0.71. Simplified CT-based atlas for delineation of the supra- and infraclavicular lymph nodes for locoregional irradiation of the breast on non-enhanced CT-scan, have been developed in this study. This atlas provides a consistent set of guidelines for delineating these volumes. Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

The pattern of prognostic and risk indicators among women with breast cancer undergoing modified radical mastectomy in Dar es Salaam, Tanzania.

PubMed

Mwakigonja, Amos R; Rabiel, Happiness; Mbembati, Naboth A; Lema, Leonard E K

2016-01-01

Breast cancer is the commonest female malignancy globally and the second (after uterine cervix) in sub-Saharan Africa including Tanzania. Prognostic indicators reportedly influence post-mastectomy adjuvant therapy by predicting risks on survival and recurrence although in Tanzania this data is lacking. Here, we evaluate the pattern of prognostic and risk indicators among women with breast cancer undergoing modified-radical-mastectomy (MRM) at Muhimbili National Hospital (MNH) and Tumaini Hospital (TH), Dar es Salaam, Tanzania. This hospital-based prospective cross-sectional study included female patients undergoing MRM from April 2011 to January 2012. Clinical stage I-III patients were enrolled after being scheduled for mastectomy. Patients with evidence of distant metastasis (stage IV) were excluded. Mastectomy and axillary lymph nodes biopsies were submitted to the Histopathology laboratory for grade, type, nodal and margins status. Data was collected using a structured questionnaire and analyzed using SPSS. A total of 348 patients were admitted with breast cancer including 86 patients (with 16 from TH having similar demography and presentation) meeting inclusion criteria. Age-range at diagnosis was 28-79 years, mean 52.1 years. Most (89 %) attained menarche after 11 years. About 56 % were postmenopausal. The majority (78 %) were multiparous with positive family history in 14.1 and 37.6 % used hormonal contraceptives. About 27.1 % were social alcohol drinkers. The majority (61 %) had T4b disease, 75.6 % had positive axillary nodes including 42.7 % with 4-9 involved nodes (N2). The commonest (91.9 %) histological type was invasive ductal carcinoma. Lobular, medullary and mucinous carcinomas were rare. Most (83.7 %) of our patients presented with stage III and the rest stage II. Intermediate- and high-grade tumors accounted for 73.5 %. Following MRM, 25 % of our patients had positive surgical margins and similarly for the base. Most of our breast cancer patients present with frequent risks including younger age, multiparity, hormonal contraceptives use, alcohol use and family history. Unfavourable prognostic indicators including late stages, large primary tumor size, skin infiltration, positive surgical margins, positive axillary lymph nodes and a high histological grade were associated. A sustainable screening program by self-examination to allow early diagnosis is needed to reduce morbidity and mortality from this cancer.

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2017-10-01

Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR...TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

Evaluation of Sentinel Lymph Node Dose Distribution in 3D Conformal Radiotherapy Techniques in 67 pN0 Breast Cancer Patients.

PubMed

Witucki, Gerlo; Degregorio, Nikolaus; Rempen, Andreas; Schwentner, Lukas; Bottke, Dirk; Janni, Wolfgang; Ebner, Florian

2015-01-01

Introduction. The anatomic position of the sentinel lymph node is variable. The purpose of the following study was to assess the dose distribution delivered to the surgically marked sentinel lymph node site by 3D conformal radio therapy technique. Material and Method. We retrospectively analysed 70 radiotherapy (RT) treatment plans of consecutive primary breast cancer patients with a successful, disease-free, sentinel lymph node resection. Results. In our case series the SN clip volume received a mean dose of 40.7 Gy (min 28.8 Gy/max 47.6 Gy). Conclusion. By using surgical clip markers in combination with 3D CT images our data supports the pathway of tumouricidal doses in the SN bed. The target volume should be defined by surgical clip markers and 3D CT images to give accurate dose estimations.

Optical characterization of ex-vivo axillary lymph nodes of breast-cancer patients using a custom-built spectrophotometer

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Saegusa-Beecroft, Emi; Mamou, Jonathan; Chitnis, Parag V.; Machi, Junji; Feleppa, Ernest J.

2014-03-01

Quantitative photoacoustics is emerging as a new hybrid modality to investigate diseases and cells in human pathology and cytology studies. Optical absorption of light is the predominant mechanism behind the photoacoustic effect. Therefore, a need exits to characterize the optical properties of specimens and to identify the relevant operating wavelengths for photoacoustic imaging. We have developed a custom low-cost spectrophotometer to measure the optical properties of human axillary lymph nodes dissected for breast-cancer staging. Optical extinction curves of positive and negative nodes were determined in the spectral range of 400 to 1000 nm. We have developed a model to estimate tissue optical properties, taking into account the role of fat and saline. Our results enabled us to select the optimal optical wavelengths for maximizing the imaging contrast between metastatic and noncancerous tissue in axillary lymph nodes.

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.

PubMed

Niemiec, Joanna; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Majchrzyk, Kaja; Kruczak, Anna; Sas-Korczyńska, Beata; Ryś, Janusz

2018-04-01

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival.

PubMed

Cao, Wenfeng; Zhang, Bin; Liu, Yanxue; Li, Hongtao; Zhang, Shiwu; Fu, Li; Niu, Yun; Ning, Liansheng; Cao, Xuchen; Liu, Zhihua; Sun, Baocun

2007-09-01

There is sufficient evidence that human stomatin-like protein 2 (SLP-2) is a novel cancer-related gene. Its protein is overexpressed in many human cancers. SLP-2 can contribute to the promotion of cell growth, cell adhesion, and tumorigenesis in esophageal squamous cell carcinoma and lymph node metastasis in laryngeal squamous cell carcinoma. Immunohistochemical detection of SLP-2, estrogen and progesterone receptors, and HER-2/neu were performed on 263 cases of primary invasive breast cancer with a tissue microarray. Of 263 cases, 138 (52.5%) showed high expression of SLP-2 protein, and 125 (47.5%) showed low or absent expression. In addition, there were significant positive associations between tumor stage and size (P = .020), lymph node metastasis (P < .001), clinical stage (P < .001), distant metastasis (P = .002), and HER-2/neu protein expression (P = .037) and high-level SLP-2 expression. High-level SLP-2 expression was associated with decreased overall survival (P = .011) and was more often found in patients with tumors larger than 20 mm, lymph node metastasis, advanced clinical stage, distant metastasis, and HER-2/neu protein-positive expression. More important, lymph node metastasis, HER-2/neu-positive expression, and high-level SLP-2 expression were associated with significantly decreased survival.

Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer

PubMed Central

Jadaliha, Mahdieh; Zong, Xinying; Malakar, Pushkar; Ray, Tania; Singh, Deepak K.; Freier, Susan M.; Jensen, Tor; Prasanth, Supriya G.; Karni, Rotem; Ray, Partha S.; Prasanth, Kannanganattu V.

2016-01-01

MALAT1 (metastasis associated lung adenocarcinoma transcript1) is a conserved long non-coding RNA, known to regulate gene expression by modulating transcription and post-transcriptional pre-mRNA processing of a large number of genes. MALAT1 expression is deregulated in various tumors, including breast cancer. However, the significance of such abnormal expression is yet to be fully understood. In this study, we demonstrate that regulation of aggressive breast cancer cell traits by MALAT1 is not predicted solely based on an elevated expression level but is context specific. By performing loss- and gain-of-function studies, both under in vitro and in vivo conditions, we demonstrate that MALAT1 facilitates cell proliferation, tumor progression and metastasis of triple-negative breast cancer (TNBC) cells despite having a comparatively lower expression level than ER or HER2-positive breast cancer cells. Furthermore, MALAT1 regulates the expression of several cancer metastasis-related genes, but displays molecular subtype specific correlations with such genes. Assessment of the prognostic significance of MALAT1 in human breast cancer (n=1992) revealed elevated MALAT1 expression was associated with decreased disease-specific survival in ER negative, lymph node negative patients of the HER2 and TNBC molecular subtypes. Multivariable analysis confirmed MALAT1 to have independent prognostic significance in the TNBC lymph node negative patient subset (HR=2.64, 95%CI 1.35 − 5.16, p=0.005). We propose that the functional significance of MALAT1 as a metastasis driver and its potential use as a prognostic marker is most promising for those patients diagnosed with ER negative, lymph node negative breast cancer who might otherwise mistakenly be stratified to have low recurrence risk. PMID:27250026

Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer.

PubMed

Jadaliha, Mahdieh; Zong, Xinying; Malakar, Pushkar; Ray, Tania; Singh, Deepak K; Freier, Susan M; Jensen, Tor; Prasanth, Supriya G; Karni, Rotem; Ray, Partha S; Prasanth, Kannanganattu V

2016-06-28

MALAT1 (metastasis associated lung adenocarcinoma transcript1) is a conserved long non-coding RNA, known to regulate gene expression by modulating transcription and post-transcriptional pre-mRNA processing of a large number of genes. MALAT1 expression is deregulated in various tumors, including breast cancer. However, the significance of such abnormal expression is yet to be fully understood. In this study, we demonstrate that regulation of aggressive breast cancer cell traits by MALAT1 is not predicted solely based on an elevated expression level but is context specific. By performing loss- and gain-of-function studies, both under in vitro and in vivo conditions, we demonstrate that MALAT1 facilitates cell proliferation, tumor progression and metastasis of triple-negative breast cancer (TNBC) cells despite having a comparatively lower expression level than ER or HER2-positive breast cancer cells. Furthermore, MALAT1 regulates the expression of several cancer metastasis-related genes, but displays molecular subtype specific correlations with such genes. Assessment of the prognostic significance of MALAT1 in human breast cancer (n=1992) revealed elevated MALAT1 expression was associated with decreased disease-specific survival in ER negative, lymph node negative patients of the HER2 and TNBC molecular subtypes. Multivariable analysis confirmed MALAT1 to have independent prognostic significance in the TNBC lymph node negative patient subset (HR=2.64, 95%CI 1.35- 5.16, p=0.005). We propose that the functional significance of MALAT1 as a metastasis driver and its potential use as a prognostic marker is most promising for those patients diagnosed with ER negative, lymph node negative breast cancer who might otherwise mistakenly be stratified to have low recurrence risk.

The Significance of the Stromal Response in Breast Cancer: An Immunohistochemical Study of Myofibroblasts in Primary and Metastatic Breast Cancer.

PubMed

Roozdar, Alale; Hayes, Malcolm M; Pourseyedei, Bahram; Zeinalinejad, Hamid; Shamsi Meymandi, Manzumeh; Dabiri, Bahram; Dabiri, Shahriar

2018-05-01

Gene expression profiling of breast cancer has demonstrated the importance of stromal response in determining the prognosis of invasive breast cancer. The host response to breast cancer is of increasing interest to pathologists and may be a future focus for novel pharmacological treatments. This study describes the pattern of distribution of stromal myofibroblasts using immunostains for CD10 and smooth muscle actin (SMA) in 50 primary breast cancers and their matched nodal metastases (68.6% nodes positive and 31.4% nodes negative). The stroma within the tumor (intratumoral) and at the advancing tumor edge (peri-tumoral) was studied in both primary and nodal sites. A simple quantitative scoring system was employed for both immunostains. The correlation between expression of these markers by stromal cells and standard pathological prognostic factors of stage, grade, hormone receptor and Her-2 status was analysed. SMA-positive stromal cells were more abundant in peri-tumoral stroma compared with intratumoral stroma in both primary and metastatic lesions. SMA expression in the lymph node metastases showed a significant correlation with tumor stage. SMA expression in peri-tumoral stroma correlated with Her-2 status. The results of this study suggest that myofibroblasts, particularly those expressing SMA, might potentiate the progression of the carcinomatous process especially in nodal metastases. Thus these cells may be a potential therapeutic target. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib.

PubMed

Park, Youngmok; Kim, Hyemin; Kim, Eui-Hyun; Suh, Chang-Ok; Lee, Soohyeon

2016-01-01

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.

Rationale of lymph node dissection for breast cancer--from the viewpoint of analysis of axillary lymphatic flow using activated carbon particle CH40.

PubMed

Sawai, K; Hagiwara, A; Shimotsuma, M; Sakakibara, T; Imanishi, T; Takemoto, Y; Takahashi, T

1996-03-01

In order to rationalize lymph node dissection for breast cancer, we reviewed regional lymphatic flow from the mesial and outer half of the breast using intra-tumoral injection of activated carbon particles (CH40). Seventy patients with breast cancer were included in this study. Cancers were located in the mesial half of the breast in 25 cases and in its outer half in 41 cases. Since regional lymph nodes were blackened by CH40, lymph node dissection was performed easily and small lymph nodes could be readily examined. The average number of resected nodes in each case was 29.4. When CH40 was injected into the mesial half of the breast, the rates of blackened nodes (number of macroscopically blackened lymph nodes/number of total removed lymph nodes) in the stations were 46.6% (No. 1a), 41.4% (No. 1b), 62.1% (No. 1c), 61.8% (No. 2), 69.2.% (No. 2h), and 65.6% (No. 3). When CH40 was injected into outer half of the breast, those were 62.0% (No. 1a), 64.3% (No. 1b), 68.7% (No. 1c), 75.3% (No. 2), and 67.8% (No. 2h). Regardless of tumor location, the rates of blackened nodes were high in each station. In conclusion, regardless of tumor location it is impossible to determine the level of axillary dissection for breast cancer. It should be all or nothing.

Increased expression of progesterone receptor membrane component 1 is associated with aggressive phenotype and poor prognosis in ER-positive and negative breast cancer.

PubMed

Ruan, Xiangyan; Zhang, Ying; Mueck, Alfred O; Willibald, Marina; Seeger, Harald; Fehm, Tanja; Brucker, Sara; Neubauer, Hans

2017-02-01

Expression of progesterone receptor membrane component 1 (PGRMC1) has been shown to be higher in breast cancer than normal tissue. We have previously shown that certain progestogens strongly stimulate proliferation of breast cancer cells overexpressing PGRMC1, and therefore hypothesize that PGRMC1 may play a critical role in breast cancer progression. Because little information is available if expression of PGRMC1 is also associated with worse prognosis for breast cancer patients, in this study we investigated the clinicopathologic significance of PGRMC1 expression in breast cancer tissue. Expression of PGRMC1 was analyzed by immunohistochemical staining of primary tumor tissues obtained from 69 breast cancer patients. A labeling score was developed, and results were correlated with tumor size, lymph node metastasis, and clinical outcome. Overexpression of PGRMC1 is correlating with larger tumor size and lymph node metastasis. Kaplan-Meier survival curves indicate that patients with PGRMC1 tumors have poorer disease-free and overall survival independent from the estrogen receptor status than breast cancer patients with PGRMC1 tumors. Our findings suggest that the expression of PGRMC1 might be useful for predicting prognosis in patients with breast cancer.

Axillary Lymph Nodes and Breast Cancer

MedlinePlus

... white blood cells that help fight illness. If breast cancer spreads, the lymph nodes in the underarm (called ... if they contain cancer cells. This helps determine breast cancer stage and guide treatment. Sentinel node biopsy and ...

Identification and analysis of CHEK2 germline mutations in Chinese BRCA1/2-negative breast cancer patients.

PubMed

Fan, Zhenhua; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xu, Ye; Xie, Yuntao

2018-05-01

Cell-cycle-checkpoint kinase 2 (CHEK2) is an important moderate-penetrance breast cancer predisposition gene; however, recurrent CHEK2 mutations found in Caucasian women are very rare in Chinese population. We investigated the mutation spectrum and clinical relevance of CHEK2 germline mutations in Chinese breast cancer patients. The entire coding regions and splicing sites of CHEK2 were screened in 7657 Chinese BRCA1/2-negative breast cancer patients, using 62-gene panel-based sequencing. Out of 7657 BRCA1/2-negative breast cancer patients, 26 (0.34%) carried CHEK2 pathogenic germline mutations. Most of these mutations (92.3%, 24/26) were nonsense or frameshift mutations; 84.6% (22/26) of them were in forkhead-associated (FHA) or kinase domains. Of the 18 types of CHEK2 mutations we found, 61.1% (11/18) of were novel mutations and two recurrent mutations (Y139X and R137X) were found in this cohort. Patients with CHEK2 mutations were significantly more likely to have family histories of breast and/or ovarian cancer (23.1% vs. 8.6%, p = 0.022) and family histories of any cancer (50.0% vs. 31.6%, p = 0.044); and were significantly more likely to have lymph node-positive (53.8% vs. 27.3%, p = 0.002) and progesterone receptor (PR)-positive (88.5% vs. 64.5%, p = 0.011) breast cancers. Among Chinese breast cancer patients, the CHEK2 germline mutation rate is approximately 0.34% and two specific mutations (Y139X and R137X) are recurrent. Patients with CHEK2 mutations are significantly more likely to have family histories of cancer, and to develop lymph node-positive and/or PR-positive breast cancers.

Effectiveness of Computer-Aided Detection in Community Mammography Practice

PubMed Central

Abraham, Linn; Taplin, Stephen H.; Geller, Berta M.; Carney, Patricia A.; D’Orsi, Carl; Elmore, Joann G.; Barlow, William E.

2011-01-01

Background Computer-aided detection (CAD) is applied during screening mammography for millions of US women annually, although it is uncertain whether CAD improves breast cancer detection when used by community radiologists. Methods We investigated the association between CAD use during film-screen screening mammography and specificity, sensitivity, positive predictive value, cancer detection rates, and prognostic characteristics of breast cancers (stage, size, and node involvement). Records from 684 956 women who received more than 1.6 million film-screen mammograms at Breast Cancer Surveillance Consortium facilities in seven states in the United States from 1998 to 2006 were analyzed. We used random-effects logistic regression to estimate associations between CAD and specificity (true-negative examinations among women without breast cancer), sensitivity (true-positive examinations among women with breast cancer diagnosed within 1 year of mammography), and positive predictive value (breast cancer diagnosed after positive mammograms) while adjusting for mammography registry, patient age, time since previous mammography, breast density, use of hormone replacement therapy, and year of examination (1998–2002 vs 2003–2006). All statistical tests were two-sided. Results Of 90 total facilities, 25 (27.8%) adopted CAD and used it for an average of 27.5 study months. In adjusted analyses, CAD use was associated with statistically significantly lower specificity (OR = 0.87, 95% confidence interval [CI] = 0.85 to 0.89, P < .001) and positive predictive value (OR = 0.89, 95% CI = 0.80 to 0.99, P = .03). A non-statistically significant increase in overall sensitivity with CAD (OR = 1.06, 95% CI = 0.84 to 1.33, P = .62) was attributed to increased sensitivity for ductal carcinoma in situ (OR = 1.55, 95% CI = 0.83 to 2.91; P = .17), although sensitivity for invasive cancer was similar with or without CAD (OR = 0.96, 95% CI = 0.75 to 1.24; P = .77). CAD was not associated with higher breast cancer detection rates or more favorable stage, size, or lymph node status of invasive breast cancer. Conclusion CAD use during film-screen screening mammography in the United States is associated with decreased specificity but not with improvement in the detection rate or prognostic characteristics of invasive breast cancer. PMID:21795668

A predictive index of axillary nodal involvement in operable breast cancer.

PubMed Central

De Laurentiis, M.; Gallo, C.; De Placido, S.; Perrone, F.; Pettinato, G.; Petrella, G.; Carlomagno, C.; Panico, L.; Delrio, P.; Bianco, A. R.

1996-01-01

We investigated the association between pathological characteristics of primary breast cancer and degree of axillary nodal involvement and obtained a predictive index of the latter from the former. In 2076 cases, 17 histological features, including primary tumour and local invasion variables, were recorded. The whole sample was randomly split in a training (75% of cases) and a test sample. Simple and multiple correspondence analysis were used to select the variables to enter in a multinomial logit model to build an index predictive of the degree of nodal involvement. The response variable was axillary nodal status coded in four classes (N0, N1-3, N4-9, N > or = 10). The predictive index was then evaluated by testing goodness-of-fit and classification accuracy. Covariates significantly associated with nodal status were tumour size (P < 0.0001), tumour type (P < 0.0001), type of border (P = 0.048), multicentricity (P = 0.003), invasion of lymphatic and blood vessels (P < 0.0001) and nipple invasion (P = 0.006). Goodness-of-fit was validated by high concordance between observed and expected number of cases in each decile of predicted probability in both training and test samples. Classification accuracy analysis showed that true node-positive cases were well recognised (84.5%), but there was no clear distinction among the classes of node-positive cases. However, 10 year survival analysis showed a superimposible prognostic behaviour between predicted and observed nodal classes. Moreover, misclassified node-negative patients (i.e. those who are predicted positive) showed an outcome closer to patients with 1-3 metastatic nodes than to node-negative ones. In conclusion, the index cannot completely substitute for axillary node information, but it is a predictor of prognosis as accurate as nodal involvement and identifies a subgroup of node-negative patients with unfavourable prognosis. PMID:8630286

Adjuvant trastuzumab with chemotherapy is effective in women with small, node-negative, HER2-positive breast cancer.

PubMed

McArthur, Heather L; Mahoney, Kathleen M; Morris, Patrick G; Patil, Sujata; Jacks, Lindsay M; Howard, Jane; Norton, Larry; Hudis, Clifford A

2011-12-15

Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node-negative HER2-positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single-institution, sequential cohort study of women with small, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted. Women with ≤ 2 cm, node-negative, HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization ≥ 2) breast cancer were identified through an institutional database. A "no-trastuzumab" cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004 and a "trastuzumab" cohort of 155 trastuzumab-treated women diagnosed between May 16, 2005 and December 31, 2008 were described. Survival and recurrence outcomes were estimated by Kaplan-Meier methods. The cohorts were similar in age, median tumor size, histology, hormone receptor status, hormone therapy, and locoregional therapy. Chemotherapy was administered in 66% and 100% of the "no trastuzumab" and "trastuzumab" cohorts, respectively. The median recurrence-free and survival follow-up was: 6.5 years (0.7-8.5) and 6.8 years (0.7-8.5), respectively, for the "no trastuzumab" cohort and 3.0 years (0.5-5.2) and 3.0 years (0.6-5.2), respectively, for the "trastuzumab" cohort. The 3-year locoregional invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival were 92% versus 98% (P = .0137), 95% versus 100% (P = .0072), 82% versus 97% (P < .0001), and 97% versus 99% (P = .18) for the "no trastuzumab" and "trastuzumab" cohorts, respectively. Women with small, node-negative, HER2+ primary breast cancers likely derive significant benefit from adjuvant trastuzumab with chemotherapy. Copyright © 2011 American Cancer Society.

Influence of previous breast surgery in sentinel lymph node biopsy in patients with breast cancer.

PubMed

López-Prior, V; Díaz-Expósito, R; Casáns Tormo, I

The aim of this study was to review the feasibility of selective sentinel lymph node biopsy in patients with previous surgery for breast cancer, as well as to examine the factors that may interfere with sentinel node detection. A retrospective review was performed on 91 patients with breast cancer and previous breast surgery, and who underwent sentinel lymph node biopsy. Patients were divided into two groups according to their previous treatment: aesthetic breast surgery in 30 patients (group I) and breast-conserving surgery in 61 (group II). Lymphoscintigraphy was performed after an intra-tumour injection in 21 cases and a peri-areolar injection in 70 cases. An analysis was made of lymphatic drainage patterns and overall sentinel node detection according to clinical, pathological and surgical variables. The overall detection of the sentinel lymph node in the lymphoscintigraphy was 92.3%, with 7.7% of extra-axillary drainages. The identification rate was similar after aesthetic breast surgery (93.3%) and breast-conserving surgery (91.8%). Sentinel lymph nodes were found in the contralateral axilla in two patients (2.2%), and they were included in the histopathology study. The non-identification rate in the lymphoscintigraphy was 7.7%. There was a significantly higher non-detection rate in the highest histological grade tumours (28.6% grade III, 4.5% grade I and 3.6% grade II). Sentinel lymph node biopsy in patients with previous breast surgery is feasible and deserves further studies to assess the influence of different aspects in sentinel node detection in this clinical scenario. A high histological grade was significantly associated with a lower detection. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

The expression status of TRX, AR, and cyclin D1 correlates with clinicopathological characteristics and ER status in breast cancer.

PubMed

Huang, Weisun; Nie, Weiwei; Zhang, Wenwen; Wang, Yanru; Zhu, Aiyu; Guan, Xiaoxiang

2016-01-01

The ER signaling pathway plays a critical role in breast cancer. ER signaling pathway-related proteins, such as TRX, AR, and cyclin D1, may have an important function in breast cancer. However, the ways that they influence breast cancer development and progression are still unclear. A total of 101 Chinese female patients diagnosed with invasive ductal breast adenocarcinoma were retrospectively enrolled in the study. The expression levels of TRX, AR, and cyclin D1 were detected by immunohistochemistry and analyzed via correlation with clinicopathological characteristics and the expression status of ER, PR, and HER2. The expression status of TRX, AR, and cyclin D1 was not associated with the patient's age, menopausal status, tumor size, or histological differentiation (P>0.05), but was positively correlated with ER and PR (P<0.001, respectively). Most (66/76, 86.8) TRX-positive patients were also HER2-positive (P=0.003). Of AR- or cyclin D1-positive patients, most had relatively earlier I-II tumor stage (P=0.005 and P=0.047, respectively) and no metastatic lymph node involvement (P=0.008 and P=0.005, respectively). TRX was found to be positively correlated with ER and PR expression, whereas it was negatively correlated with HER2 expression. In addition, we found that the positive expression of AR and cyclin D1 was correlated with lower TNM stage and fewer metastatic lymph nodes, and it was more common in ER-positive breast cancer than in the basal-like subtype. This may indicate that AR and cyclin D1 are good predictive and prognostic factors and closely interact with ER signaling pathway. Further studies will be necessary to investigate the response and clinical outcomes of treatment targeting TRX, AR, and cyclin D1.

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

PubMed

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre; Cronin, Maureen; Baehner, Frederick L; Walker, Michael G; Watson, Drew; Park, Taesung; Hiller, William; Fisher, Edwin R; Wickerham, D Lawrence; Bryant, John; Wolmark, Norman

2004-12-30

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. Copyright 2004 Massachusetts Medical Society.

Adjuvant Chemotherapy and Trastuzumab Is Safe and Effective in Older Women With Small, Node-Negative, HER2-Positive Early-Stage Breast Cancer.

PubMed

Cadoo, Karen A; Morris, Patrick G; Cowell, Elizabeth P; Patil, Sujata; Hudis, Clifford A; McArthur, Heather L

2016-12-01

The benefit of adjuvant trastuzumab with chemotherapy is well established for women with higher risk human epidermal growth factor receptor 2-positive (HER2 + ) breast cancer. However, its role in older patients with smaller, node-negative tumors is less clear. We conducted a retrospective, sequential cohort study of this population to describe the impact of trastuzumab on breast cancer outcomes and cardiac safety. Women ≥ 55 years with ≤ 2 cm, node-negative, HER2 + breast cancer were identified and electronic medical records reviewed. A no-trastuzumab cohort of 116 women diagnosed between January 1, 1999 and May 14, 2004 and a trastuzumab cohort of 128 women diagnosed between May 16, 2006 and December 31, 2010 were identified. Overall survival and distant relapse-free survival were estimated by Kaplan-Meier methods. The median ages of the trastuzumab and no-trastuzumab cohorts were 62 and 64 years, respectively. More patients in the trastuzumab cohort had grade III (P = .001), lymphovascular invasion (P = .001), or estrogen receptor-negative (P < .001) cancers. The majority of the trastuzumab cohort received chemotherapy versus one-half of the no-trastuzumab cohort (98% vs. 53%; P < .0001). The median follow-up was 4 versus 9 years in the trastuzumab versus no-trastuzumab cohorts; therefore, outcomes at 4 years are reported. Despite the higher-risk tumor features in the trastuzumab group, the 4-year overall survival was 99% in both cohorts; the distant relapse-free survival was 99% versus 97% in the trastuzumab versus no-trastuzumab cohorts. Four (3.1%; 95% confidence interval, 1.0%-7.8%) women in the trastuzumab cohort and 1 in the no-trastuzumab cohort developed symptomatic heart failure. There were no cardiac-related deaths in either arm. Following adjuvant trastuzumab with chemotherapy, selected older women with small, node-negative, HER2 + breast cancers have excellent disease control. The rate of cardiac events is low. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience.

PubMed

Sarici, Furkan; Babacan, Taner; Buyukhatipoglu, Hakan; Balakan, Ozan; Sever, Ali R; Kertmen, Neyran; Unlu, Ozan; Ates, Ozturk; Diker, Omer; Akin, Serkan; Sunar, Veli; Karakas, Yusuf; Lacin, Sahin; Altundag, Kadri

2016-01-01

Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.

Use of Exogenous Progestins and Risk or In Situ and Invasive Breast Cancer

DTIC Science & Technology

2011-10-01

will be funded by the parent R01 (NCI) grant, and not by the Era of Hope Scholar Award. Table 1: Participant enrollment report Project 2 Project 1...of lobular tumors that were node positive, PR+, e-cadherin negative , and had low p21 expression (Table 6). No differences were seen across the other...Node negative 61% 1.2 (0.8-2.0) 63% 1.9 (1.04-3.4) Node positive 31% 0.9 (0.5-1.7) 37% 3.7 (1.8-7.8) PR+ 89% 1.2 (0.8-1.9) 84% 2.9 (1.7-5.1) PR- 11

Selective sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: results of the GEICAM 2005-07 study.

PubMed

Piñero-Madrona, Antonio; Escudero-Barea, María J; Fernández-Robayna, Francisco; Alberro-Adúriz, José A; García-Fernández, Antonio; Vicente-García, Francisco; Dueñas-Rodriguez, Basilio; Lorenzo-Campos, Miguel; Caparrós, Xavier; Cansado-Martínez, María P; Ramos-Boyero, Manuel; Rojo-Blanco, Roberto; Serra-Genís, Constantí

2015-01-01

A controversial aspect of breast cancer management is the use of sentinel lymph node biopsy (SLNB) in patients requiring neoadjuvant chemotherapy (NCT). This paper discusses the detection rate (DT) and false negatives (FN) of SLNB after NCT to investigate the influence of initial nodal disease and the protocols applied. Prospective observational multicenter study in women with breast cancer, treated with NCT and SLNB post-NCT with subsequent lymphadenectomy. DT and FN rates were calculated, both overall and depending on the initial nodal status or the use of diagnostic protocols pre-SLNB. No differences in DT between initial node-negative cases and positive cases were found (89.8 vs. 84.4%, P=.437). Significant differences were found (94.1 vs. 56.5%, P=0,002) in the negative predictive value, which was lower when there was initial lymph node positivity, and a higher rate of FN, not significant (18.2 vs. 43.5%, P=.252) in the same cases. The axillary study before SLNB and after the NCT, significantly decreased the rate of FN in patients with initial involvement (55.6 vs 12.5, P=0,009). NCT means less DT and a higher rate of FN in subsequent SLNB, especially if there is initial nodal involvement. The use of protocols in axillary evaluation after administering the NCT and before BSGC, decreases the FN rate in these patients. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Ethnic disparities in breast cancer between Central Europe Caucasian women of Slavic origin and Middle East Turkish subjects.

PubMed

Zubor, P; Caliskan, M; Kajo, K; Soybir, G; Topuzlu, C; Danko, J

2013-09-20

The biological, cultural, behavioral and sociodemographic differences across populations modulate breast cancer profile among races or ethnics. Following this, we aimed to identify differences in breast cancer epidemiology, histopathology, and clinical presentation from representatives of central Europe (Slovakia) and Middle-East countries (Turkey) to point on ethnic disparities in cancer biology. The population based cross-sectional study analyzing 414 cases of primary breast carcinomas where 214 represented Caucasian and 200 Turkish subjects. The differences were found for age at the time of diagnosis (<0.0001), education, menopausal status (<0.001), tumor localization (<0.01), size (<0.0001), grade (<0.05) and axillary lymph node status (<0.001) between groups. Although carcinomas in Slovak subjects were of higher grade, negative axillary nodal status was more frequent finding compared to Turkish patients (50.0 vs. 41.0%). The Slovak group showed carcinomas to be more often ER positive (72.4 vs. 54.0%; <0.001), ER/PgR positive (54.6 vs. 49.0%; <0.001), of better Nottingham prognostic index (<0.001), and less frequent Her-2 positive (21.2 vs. 28.5%). Slovak population expressed significantly higher risk of non-sentinel lymph node metastases with increased tumor size, grade, vascular invasion and Her-2 positivity compared to Turkey population. The tumor size >2 cm and high tumor grade (G3) bears a risk of OR=7.62 and OR=3.10 in Slovak compared to OR=3.94 and OR=1.79 in Turkish cases, respectively.There are wide demographic and biological disparities in breast cancer between observed ethnics providing unique information for clinicians working at the level of screening or therapy in these populations. Keywords: breast cancer; ethnic; race; disparity; cancer biology.

A 16 Yin Yang gene expression ratio signature for ER+/node- breast cancer.

PubMed

Xu, Wayne; Jia, Gaofeng; Cai, Nianguang; Huang, Shujun; Davie, James R; Pitz, Marshall; Banerji, Shantanu; Murphy, Leigh

2017-03-15

Breast cancer is one of the leading causes of cancer death in women. It is a complex and heterogeneous disease with different clinical outcomes. Stratifying patients into subgroups with different outcomes could help guide clinical decision making. In this study, we used two opposing groups of genes, Yin and Yang, to develop a prognostic expression ratio signature. Using the METABRIC cohort we identified a16-gene signature capable of stratifying breast cancer patients into four risk levels with intention that low-risk patients would not undergo adjuvant systemic therapy, intermediate-low-risk patients will be treated with hormonal therapy only, and intermediate-high- and high-risk groups will be treated by chemotherapy in addition to the hormonal therapy. The 16-gene signature for four risk level stratifications of breast cancer patients has been validated using 14 independent datasets. Notably, the low-risk group (n = 51) of 205 estrogen receptor-positive and node negative (ER+/node-) patients from three different datasets who had not had any systemic adjuvant therapy had 100% 15-year disease-specific survival rate. The Concordance Index of YMR for ER+/node negative patients is close to the commercially available signatures. However, YMR showed more significance (HR = 3.7, p = 8.7e-12) in stratifying ER+/node- subgroup than OncotypeDx (HR = 2.7, p = 1.3e-7), MammaPrint (HR = 2.5, p = 5.8e-7), rorS (HR = 2.4, p = 1.4e-6), and NPI (HR = 2.6, p = 1.2e-6). YMR signature may be developed as a clinical tool to select a subgroup of low-risk ER+/node- patients who do not require any adjuvant hormonal therapy (AHT). © 2016 UICC.

Optical see-through cancer vision goggles enable direct patient visualization and real-time fluorescence-guided oncologic surgery

PubMed Central

Mondal, Suman B.; Gao, Shengkui; Zhu, Nan; Hebimana-Griffin, LeMoyne; Akers, Walter J.; Liang, Rongguang; Gruev, Viktor; Margenthaler, Julie; Achilefu, Samuel

2017-01-01

Background The inability to directly visualize the patient and surgical site limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment. Methods We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided popliteal lymph node resection. Four breast cancer patients received 99mTc-sulfur colloid and indocyanine green retroareolarly, before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment. Results Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and 4 pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin embedded section histopathology. Conclusions The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room. PMID:28213790

Optical See-Through Cancer Vision Goggles Enable Direct Patient Visualization and Real-Time Fluorescence-Guided Oncologic Surgery.

PubMed

Mondal, Suman B; Gao, Shengkui; Zhu, Nan; Habimana-Griffin, LeMoyne; Akers, Walter J; Liang, Rongguang; Gruev, Viktor; Margenthaler, Julie; Achilefu, Samuel

2017-07-01

The inability to visualize the patient and surgical site directly, limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment. We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared, fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided, tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided, popliteal lymph node resection. Four breast cancer patients received 99m Tc-sulfur colloid and indocyanine green retroareolarly before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment. Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and four pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67 ± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin-embedded section histopathology. The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room.

Dose-intensified epirubicin versus standard-dose epirubicin/cyclophosphamide followed by CMF in breast cancer patients with 10 or more positive lymph nodes: results of a randomised trial (GABG-IV E-93) - the German Adjuvant Breast Cancer Group.

PubMed

Eiermann, Wolfgang; Graf, Erika; Ataseven, Beyhan; Conrad, Bettina; Hilfrich, Jörn; Massinger-Biebl, Heidi; Vescia, Sabine; Loibl, Sibylle; von Minckwitz, Gunter; Schumacher, Martin; Kaufmann, Manfred

2010-01-01

To compare dose-intensified epirubicin monotherapy with a standard sequential regimen, patients with primary breast cancer and > or =10 involved axillary nodes were randomised to either four 21-day cycles of epirubicin 120 mg/m(2) (E120; n=202) or four 21-day cycles of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) (EC) followed by three 28-day cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF; n=209). Simultaneous hormonal treatment was applied in both arms. At 5 years' median follow-up, the 5-year event-free survival (EFS) rates were 47.7% (95% confidence interval [CI], 40.2-55.2%) for E120 and 45.9% (38.5-53.3%) for EC-CMF. E120 was as effective as EC-CMF with regard to EFS (hazard ratio [HR] for E120 versus EC-CMF 1.04; 95% CI, 0.79-1.36; p=0.79) and overall survival (HR 1.06; 95% CI 0.77-1.46; p=0.72). The data demonstrate that 4 cycles of dose-intensified epirubicin monotherapy can be as effective as 7 cycles of standard sequential polychemotherapy in high-risk breast cancer patients with > or =10 positive lymph nodes, despite treatment with a single agent and a shorter treatment duration.

Management of Adenoid Cystic Carcinoma of the Breast: A Rare Cancer Network Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khanfir, Kaouthar, E-mail: kaouthar.khanfir@rsv-gnw.ch; Kallel, Adel; Villette, Sylviane

2012-04-01

Background: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC. Methods: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy). Results: With a median follow-upmore » of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT. Conclusion: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery.« less

US surveillance of regional lymph node recurrence after breast cancer surgery.

PubMed

Moon, Hee Jung; Kim, Min Jung; Kim, Eun-Kyung; Park, Byeong-Woo; Youk, Ji Hyun; Kwak, Jin Young; Sohn, Joohyuk; Kim, Seung-Il

2009-09-01

To determine the diagnostic indexes of lymph node ultrasonography (US) of the axillary and supraclavicular regions for detecting lymph node recurrence (LNR) after breast cancer surgery and assess the effect of lymph node evaluation on prognosis during bilateral breast US. Institutional review board approved this retrospective study and waived informed consent. Between January 2003 and December 2004, 3982 lymph node US examinations, including bilateral axillary and supraclavicular areas, were performed in 1817 women (mean age, 49.9 years; range, 22-86 years) after breast cancer surgery, nine of whom had palpable lesions. Final diagnosis was based on cytopathologic results, clinical follow-up, and imaging studies for at least 12 months after breast US. Diagnostic indexes of US for detecting LNR were assessed. The frequency of distant metastases between patients with ipsilateral LNR and those without was compared. Three-year mortality rates of patients with ipsilateral LNR only and those with distant metastases were evaluated. Of 1817 patients, 54 had suspicious LNR at US (28 at first, 20 at second, five at third, and one at fourth US examination). Thirty-nine of 1817 patients (2.1%), including nine with palpable lesions, had LNR, 11 of whom had ipsilateral LNR only. At first lymph node US, LNR was detected in 17 patients; at second, in 10; at third, in two; and at fourth, in one. Nine had false-negative results. The respective sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of lymph node US for detecting LNR per woman was 76.9% (30 of 39), 98.7% (1754 of 1778), 98.2% (1784 of 1817), 55.6% (30 of 54), and 99.5% (1754 of 1763); those of first lymph node US were 85.0% (17 of 20), 99.4% (1786 of 1797), 99.2% (1803 of 1817), 60.7% (17 of 28), and 99.8% (1786 of 1789); and those of total US examinations were 78.0% (32 of 41), 99.4% (3917 of 3941), 99.2% (3949 of 3982), 57.1% (32 of 56), and 99.8% (3917 of 3926). Distant metastases were found more frequently in patients with ipsilateral LNR (62%) than in those without (2.3%) (P < .0001). The 3-year mortality rate of patients with ipsilateral LNR only was significantly lower than that in patients with distant metastases (P = .03). Ipsilateral LNR is a predictor of distant metastasis, and lymph node evaluation during breast US is useful for early detection of LNR in asymptomatic patients.

Hormone Receptor Status in Breast Cancer and its Relation to Age and Other Prognostic Factors

PubMed Central

Pourzand, Ali; Fakhree, M. Bassir A.; Hashemzadeh, Shahryar; Halimi, Monireh; Daryani, Amir

2011-01-01

Background: Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers. Patients and methods: We organized an analytic cross-sectional study of 105 women diagnosed with breast cancer who have been operated on between 2008 to 2010. We evaluated age, size, hormone receptor status, HER-2 and P53 expression as possible indicator of lymph node involvement. Results: There is a direct correlation between positive progesterone receptor status and being younger than 40 (P < 0.05). Also, compared with older women, young women had tumors that were more likely to be large in size and have higher stages (P < 0.05). Furthermore patients with negative progesterone receptor status were more likely to have HER-2 overexpression (P < 0.05). The differences in propensity to lymph node metastasis between hormone receptor statuses were not statically significant. Conclusions: Although negative progesterone receptor tumors were more likely to have HER-2 overexpression, it is possible that higher stage and larger size breast cancer in younger women is related to positive progesterone receptor status. PMID:21695095

The relevance of ultrasound imaging of suspicious axillary lymph nodes and fine-needle aspiration biopsy in the post ACOSOG Z11 era in early breast cancer

PubMed Central

Vijayaraghavan, Gopal R.; Vedantham, Srinivasan; Kataoka, Milliam; DeBenedectis, Carolynn; Quinlan, Robert

2016-01-01

Rationale and Objective Evaluation of nodal involvement in early-stage breast cancers (T1 or T2) changed following the Z11 trial; however, not all patients meet the Z11 inclusion criteria. Hence, the relevance of ultrasound imaging of the axilla and fine-needle aspiration biopsy (FNA) in early-stage breast cancers was investigated. Materials and Methods In this single-center, retrospective study, 758 subjects had pathology-verified breast cancer diagnosis over a 3-year period, of which 128 subjects with T1/T2 breast tumors had abnormal axillary lymph nodes on ultrasound, had FNA, and proceeded to axillary surgery. Ultrasound images were reviewed and analyzed using multivariable logistic regression to identify the features predictive of positive FNA. Accuracy of FNA was quantified as the area under the receiver operating characteristic curve with axillary surgery as reference standard. Results Of 128 subjects, 61 and 65 were positive on FNA and axillary surgery, respectively. Sensitivity, specificity, positive- and negative-predictive values of FNA were 52/65 (80%), 54/63 (85.7%), 52/61(85.2%) and 54/67 (80.5%), respectively. After adjusting for neoadjuvant chemotherapy between FNA and surgery, a positive FNA was associated with higher likelihood for positive axillary surgery (odds ratio: 22.7; 95% CI: 7.2–71.3, p<0.0001), and the accuracy of FNA was 0.801 (95% CI: 0.727–0.876). Among ultrasound imaging features, cortical thickness and abnormal hilum were predictive (p<0.017) of positive FNA with accuracy of 0.817 (95% CI: 0.741–0.893). Conclusion Ultrasound imaging and FNA can play an important role in the management of early breast cancers even in the post-Z11 era. Higher weightage can be accorded to cortical thickness and hilum during ultrasound evaluation. PMID:27916595

Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer.

PubMed

Azghadi, Soheila; Daly, Megan; Mayadev, Jyoti

2016-10-01

Recent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. A customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). A total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further axillary involvement, with no difference between the academic and community radiation oncologists (P = .11). In SLN biopsy-positive early-stage breast cancer with omission of completion ALND, axillary RT is increasing used to cover the undissected axilla. Most respondents use SCF or AX for patients with low to intermediate pathologic features. Online prediction nomograms are used by a few practitioners to assist in clinical decision-making in this setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Conservative treatment versus mastectomy in breast cancer tumors with macroscopic diameter of 20 millimeters or less. The experience of the Institut Gustave-Roussy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarrazin, D.; Le, M.; Roueesse, J.

1984-03-01

A clinical trial was conducted at the Institut Gustave Roussy between October 1972 and December 1980 to compare mastectomy with local excision plus Cobalt-irradiation, in patients with breast cancer tumors of 20 mm in diameter or less at macroscopic examination. Low-axillary dissection and extemporaneous histologic examination were carried out for all patients. If one or more positive nodes were found, complete axillary dissection was performed. The study included 179 patients. No significant difference was detected in either overall or relapse-free survival between the two groups, although the conservatively treated group showed slightly better results. The results of conservative treatment weremore » esthetically satisfactory in 92% of the cases. The trial included a second randomization for the patients with positive axillary nodes to assess the value of nodal area irradiation; 72 patients were studied in this part of the trial. No significant differences were found between the two groups after adjustment for the number of positive axillary nodes, although the no-nodal irradiation group showed better results and less complications than the nodal irradiation group.« less

Predictive Value of Primary Tumor Site for Loco-regional Recurrence in Early Breast Cancer Patients with One to Three Positive Axillary Lymphadenophy.

PubMed

Niu, Shaoqing; Wen, Ge; Ren, Yufeng; Li, Yiyang; Feng, Lingling; Wang, Chengtao; Huang, Xiaobo; Wen, Bixiu; Zhang, Yujing

2017-01-01

Introduction: It remains controversial on high risks for early breast cancer patients with one to three axillary nodes after mastectomy who is predisposition to locoregional recurrence. The present study is to investigate the relationship between primary tumor site and loco-regional recurrence (LRR) and explore the predictive value of clinicopathological characteristics in LRR for early breast cancer patients with one to three positive axillary lymph nodes after mastectomy. Methods: We reviewed the clinical data of 656 consecutively diagnosed patients with pT 1-2 N 1 M 0 breast cancer who were treated in Sun Yat-sen University Cancer Center with radical operation without postoperative radiotherapy between March 1998 and December 2010. The primary tumor sites included outer quadrant in 455 patients (69.36%), inner quadrant in 156 patients (23.78%)and central quadrant in 45 patients (6.86%). LRR and LRR-free survival (LRFS) in combination with clinical and pathological features were analyzed to screen out patients with higher risk of LRR. Results: The median follow-up time was 64.9 months. The 5-, 10-year LRR for the cohort was 8.6% and 12.9%, respectively; the 5-, 10-year LRFS was 86.2% and 76.4%, respectively. Multivariate analyses showed that age of ≤35 years, inner quadrant tumor and non-luminal subtype were independent risk factors for LRR and LRFS. Patients with primary tumor in inner quadrant showed higher LRR and poorer LRFS when risk factors are ≥2 than those with tumors in other sites. Conclusions: Inner quadrant tumor was an independent predictor for LRR and LRFS in patients with early breast cancer and one to three positive axillary lymph nodes, which would be more accurate in combination with other prognostic indexes including patients' age, pathological T stage, Ki67 status, molecular subtypes.

German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer.

PubMed

von Minckwitz, Gunter; Möbus, Volker; Schneeweiss, Andreas; Huober, Jens; Thomssen, Christoph; Untch, Michael; Jackisch, Christian; Diel, Ingo J; Elling, Dirk; Conrad, Bettina; Kreienberg, Rolf; Müller, Volkmar; Lück, Hans-Joachim; Bauerfeind, Ingo; Clemens, Michael; Schmidt, Marcus; Noeding, Stefanie; Forstbauer, Helmut; Barinoff, Jana; Belau, Antje; Nekljudova, Valentina; Harbeck, Nadia; Loibl, Sibylle

2013-10-01

Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use. The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed. Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093). Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.

Sentinel lymph node biopsy in breast cancer

PubMed Central

Alsaif, Abdulaziz A.

2015-01-01

Objectives: To report our experience in sentinel lymph node biopsy (SLNB) in early breast cancer. Methods: This is a retrospective study conducted at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between January 2005 and December 2014. There were 120 patients who underwent SLNB with frozen section examination. Data collected included the characteristics of patients, index tumor, and sentinel node (SN), SLNB results, axillary recurrence rate and SLNB morbidity. Results: There were 120 patients who had 123 cancers. Sentinel node was identified in 117 patients having 120 tumors (97.6% success rate). No SN was found intraoperatively in 3 patients. Frozen section results showed that 95 patients were SN negative, those patients had no immediate axillary lymph node dissection (ALND), whereas 25 patients were SN positive and subsequently had immediate ALND. Upon further examination of the 95 negative SN’s by hematoxylin & eosin (H&E) and immunohistochemical staining for doubtful H&E cases, 10 turned out to have micrometastases (6 had delayed ALND and 4 had no further axillary surgery). Median follow up of patients was 35.5 months and the mean was 38.8 months. There was one axillary recurrence observed in the SN negative group. The morbidity of SLNB was minimal. Conclusion: The obtainable results from our local experience in SLNB in breast cancer, concur with that seen in published similar literature in particular the axillary failure rate. Sentinel lymph node biopsy resulted in minimal morbidity. PMID:26318461

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karlsson, Per, E-mail: per.karlsson@oncology.gu.se; Cole, Bernard F.; Price, Karen N.

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. Formore » patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.« less

Supine MRI for regional breast radiotherapy: imaging axillary lymph nodes before and after sentinel-node biopsy

NASA Astrophysics Data System (ADS)

van Heijst, Tristan C. F.; Eschbach-Zandbergen, Debora; Hoekstra, Nienke; van Asselen, Bram; Lagendijk, Jan J. W.; Verkooijen, Helena M.; Pijnappel, Ruud M.; de Waard, Stephanie N.; Witkamp, Arjen J.; van Dalen, Thijs; Desirée van den Bongard, H. J. G.; Philippens, Marielle E. P.

2017-08-01

Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p  <  0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible.

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance)

PubMed Central

Boughey, Judy C.; Ballman, Karla V.; Hunt, Kelly K.; McCall, Linda M.; Mittendorf, Elizabeth A.; Ahrendt, Gretchen M.; Wilke, Lee G.; Le-Petross, Huong T.

2015-01-01

Purpose The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients and Methods Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Results Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. Conclusion AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. PMID:25646192

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance).

PubMed

Boughey, Judy C; Ballman, Karla V; Hunt, Kelly K; McCall, Linda M; Mittendorf, Elizabeth A; Ahrendt, Gretchen M; Wilke, Lee G; Le-Petross, Huong T

2015-10-20

The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. © 2015 by American Society of Clinical Oncology.

Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis.

PubMed

Abrams, Matthew J; Koffer, Paul P; Wazer, David E; Hepel, Jaroslaw T

2017-06-01

Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor-positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). There may be a survival benefit with the addition of PMRT for male breast cancer with node-positive disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abrams, Matthew J., E-mail: mabrams@tuftsmedicalcenter.org; Koffer, Paul P.; Wazer, David E.

Purpose: Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Methods and Materials: The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overallmore » survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. Results: A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor–positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). Conclusions: There may be a survival benefit with the addition of PMRT for male breast cancer with node-positive disease.« less

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2014 CFR

2014-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2013 CFR

2013-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2012 CFR

2012-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

Irradiation doses on thyroid gland during the postoperative irradiation for breast cancer.

PubMed

Akın, Mustafa; Ergen, Arzu; Unal, Aysegul; Bese, Nuran

2014-01-01

Thyroid gland is one of the radiosensitive endocrine organs in the body. It has been shown that direct irradiation of thyroid with total doses of 26 to 30 Gy can lead to functional abnormalities. In this study, irradiation doses on thyroid gland of the patients who received postoperative chest-wall/breast and regional nodal irradiation were assessed. Retrospective analyses of treatment plans from 122 breast cancer patients who were treated with 3D conformal radiotherapy (3D CRT) planning was performed. All patients received irradiation to supraclavicular/level III lymph nodes in addition to chest-wall/breast. A total dose of 46 Gy was delivered in 25 days to supraclavicular/level III lymph node region while a total dose of 50 Gy was delivered to whole breast/chest-wall. Thyroid gland was contoured on 2-5 mm thickness of computed tomography scans. Absolute thyroid volume, mean thyroid doses were calculated. The mean thyroid volume of all patients was 16.7 cc (min: 1.9 cc, max: 41.6 cc). The mean irradiation dose on was 22.5 Gy (0.32 Gy-46.5 Gy). The level of dose was higher than 26 Gy in 44% of the patients. In majority of the node-positive breast cancer patients treated with 3D CRT, the thyroid gland was exposed to considerable doses. On the other hand, for 44% of the patients are at risk for developing thyroid function abnormalities which should be considered during the routine follow-up.

Expression of survivin and clinical correlation in patients with breast cancer.

PubMed

Sohn, Doo Min; Kim, Sung Yong; Baek, Moo Jun; Lim, Cheol Wan; Lee, Min Hyuk; Cho, Moo Sik; Kim, Tae Yoon

2006-07-01

Survivin is a member of the inhibitor of apoptosis (IAP) family, which is also involved in the regulation of cell division and is also overexpressed and associated with parameters of poor prognosis in most human cancers, including carcinomas of the lung, breast, colon, stomach, esophagus and pancreas. This study examined the expression patterns of survivin in normal breast tissue, atypical hyperplasia, primary breast cancer and lymph node tissues involved in breast cancer and determined whether the expression of survivin is associated with the characteristics and prognosis of breast cancer. Formalin-fixed paraffin-embedded samples from 80 breast cancer, 20 atypical hyperplasia and 20 malignant lymph node tissue cases were immunostained using polyclonal survivin (Novus Biologicals, CO, USA). The degree of immunostaining was recorded on a scale of 0-3 according to the percentages of staining and distributions within the cytoplasm and nucleus. Survivin was expressed in 52, 14 and 17 of the 80 breast cancer (65%), atypical hyperplasia (70%) and breast cancer lymphoid (85%) specimens, respectively. Among those expressing cancer, 11.3%, 31.3% and 22.5% demonstrated only nuclear staining, only cytoplasmic staining and both nuclear and cytoplasmic staining, respectively. A statistical analysis revealed that cytoplasmic survivin expression was correlated with the stage, histological grade and L/N metastasis. In a Cox proportional hazard model analysis, the expression of survivin was not identified as a significant independent predictor of overall survival (P=0.168), although the decrease in the survival rate of survivin-positive patients did reach statistical significance (P=0.048). our results show that survivin is frequently overexpressed in primary breast cancer and its expression gradually increased from normal breast tissue to malignant lymph nodes. The expression of cytoplasmic survivin was common in breast cancer and could be both a useful diagnostic marker and an important source of prognostic information.

Coexpression of α6β4 Integrin and Guanine Nucleotide Exchange Factor Net1 Identifies Node-Positive Breast Cancer Patients at High Risk for Distant Metastasis

PubMed Central

Gilcrease, Michael Z.; Kilpatrick, Shannan K.; Woodward, Wendy A.; Zhou, Xiao; Nicolas, Marlo M.; Corley, Lynda J.; Fuller, Gregory N.; Tucker, Susan L.; Diaz, Leslie K.; Buchholz, Thomas A.; Frost, Jeffrey A.

2009-01-01

Preclinical data indicate that α6β4 integrin signaling through Ras homolog gene family, member A, plays an important role in tumor cell motility. The objective of this study was to determine whether the combined expression of α6β4 integrin and neuroepithelioma transforming gene 1 (Net1), a guanine nucleotide exchange factor specific for Ras homolog gene family member A, is associated with adverse clinical outcome in breast cancer patients. Immunohistochemical expression of each protein was evaluated in a tumor tissue microarray prepared from the primary tumors of 94 node-positive patients with invasive breast carcinoma treated with total mastectomy and doxorubicin-based chemotherapy without radiation with a median follow-up of 12.5 years. Associations between staining results and multiple clinicopathologic variables were investigated. Although there was no significant association between α6β4 integrin or Net1 expression and clinical outcome when each marker was considered individually, coexpression of α6β4 and Net1 was associated with decreased distant metastasis–free survival (P = 0.030). In the subset of patients with hormone receptor–positive tumors, coexpression of α6β4 and Net1 was associated with a decrease in distant metastasis–free and overall survival (P < 0.001 and P = 0.006, respectively). Although an association between human epidermal growth factor receptor 2 expression and coexpression of α6β4 and Net1 (P = 0.008) was observed, coexpression of α6β4 and Net1 (hazard ratio, 1.63; P = 0.02) and lymphovascular invasion (hazard ratio, 2.35; P = 0.02) were the only factors independently associated with the development of distant metastasis in multivariate analysis. These findings suggest that coexpression of α6β4 integrin and Net1 could be a useful biomarker for aggressive disease in node-positive breast cancer patients. PMID:19124484

Quantitation of Vascular Endothelial Growth Factor and Interleukin-6 in Different Stages of Breast Cancer.

PubMed

Raghunathachar Sahana, Kabbathi; Akila, Prashant; Prashant, Vishwanath; Sharath Chandra, Bellekere; Nataraj Suma, Maduvanahalli

2017-10-01

Determination of the impact of angiogenesis on tumor development and progression is essential. This study aimed to determine the serum levels of Vascular endothelial growth factor (VEGF) and Interleukin 6 (IL-6) in breast carcinoma, and to correlate them with tumor size, lymph node involvement, and cancer stage. Under aseptic precautions 5 ml of venous blood was collected from 37 breast cancer patients and 20 healthy females after obtaining due consent and ethical committee clearance. Serum levels of VEGF and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). Serum IL-6 and VEGF levels were both significantly greater in patients than controls (P = 0.001, P = 0.001, respectively). The serum IL-6 and VEGF levels also significantly correlated with TNM staging (P = 0.001, P = 0.001). Serum IL-6 and VEGF positively correlated with each other (r 2 = 0.668, P = 0.01). Serum IL-6 and VEGF levels did not correlate with tumor size (P = 0.45, P = 0.17) or lymph node metastasis (P = 0.95, P = 0.68). Serum IL-6 and VEGF were greater in breast cancer patients than controls. The levels increased with advanced tumor, nodes, metastasis (TNM) staging, thus correlating with the patients' prognoses. Serum IL-6 and VEGF levels can be used as diagnostic tools and prognostic factors in breast cancer.

Assessment of Ultrasound Features Predicting Axillary Nodal Metastasis in Breast Cancer: The Impact of Cortical Thickness

PubMed Central

Stachs, A.; Thi, A. Tra-Ha; Dieterich, M.; Stubert, J.; Hartmann, S.; Glass, Ä.; Reimer, T.; Gerber, B.

2015-01-01

Purpose: To evaluate the accuracy of axillary ultrasound (AUS) in detecting nodal metastasis in patients with early-stage breast cancer and to identify AUS features with high predictive power. Materials and Methods: Prospective single-center preliminary study in 105 patients with a primary diagnosis of breast cancer and clinically negative axilla. AUS was performed using a 12 MHz linear-array transducer before ultrasound-guided needle biopsy. Nodal characteristics (shape, longitudinal-transverse [LT] axis ratio, margins, cortical thickness, hyperechoic hilum) were correlated with histopathological nodal status after SLNB or axillary lymph node dissection (ALND). Results: Nodal metastases were present in 42/105 patients (40.0%). Univariate analyses showed that absence of hyperechoic hilum, round shape, LT axis ratio<2, sharp margins and cortical thickness>3 mm were associated with lymph node metastasis. Multivariate logistic regression analysis revealed cortical thickness > 3 mm as an independent predictive parameter for nodal involvement. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 66.7, 74.6, 63.6, 77.0% and 71.4% respectively when cortical thickness > 3 mm was applied as the criterion for AUS positivity. Axillary tumor volume was low in patients with pT1/2 tumors and negative AUS, since only 3.2% of patients had > 2 metastatic lymph nodes. Conclusion: Cortical thickness>3 mm is a reliable predictor of nodal metastatic involvement. Negative AUS does not exclude lymph node metastases, but extensive axillary tumor volume is rare. PMID:27689144

[A Case of Noninvasive Ductal Carcinoma of the Breast in a Male].

PubMed

Yamashita, Yamato; Ishiba, Toshiyuki; Oda, Goshi; Nakagawa, Tsuyoshi; Aburatani, Tomoki; Ogo, Taiichi; Nakashima, Yutaka; Baba, Hironobu; Hoshino, Naoaki; Nishioka, Yoshinobu; Kawano, Tatsuyuki; Itoh, Takashi; Kirimura, Susumu; Kobayashi, Hirotoshi

2017-11-01

Breast cancer in male is rare, accounting for 1%of all breast cancers.Among male breast cancers, noninvasive carcinoma is extremely rare.We experienced a case of noninvasive carcinoma of the breast in a male.A 72-year-old male was referred to our hospital with a chief complaint of the tumor and blood secretion from the left nipple.Mammography revealed a highdensity mass.Ultrasound examination revealed low echoic mass at the E area, and it measured 1.5 cm.Core needle biopsy failed to provide a definitive diagnosis, and we performed an excisional biopsy of the tumor.The pathological diagnosis was noninvasive ductal carcinoma.He underwent a mastectomy without sentinel lymph node biopsy because the resection margin was positive.The patient received no adjuvant therapy and the patient's postoperative course was uneventful for 1 year.As there have been few reports on male noninvasive ductal carcinoma, we do not have evidence for indication of the sentinel lymph nodes and postoperative adjuvant therapy such as tamoxifen.We may confuse the treatment policy.

64Cu-DOTA-Trastuzumab PET Imaging in Women with HER2-Overexpressing Breast Cancer

DTIC Science & Technology

2013-10-01

3 4 HER2 IHC31 2 5 7 IHC21/FISH positive 1 1 Sites of metastatic disease Bone 2 4 6 Lymph nodes 2 5 7 Liver 2 2 4 Lung 1 1 2 Pleural effusion 1 1...and were seen in bone, lymph nodes, liver, lung, pleural effusions , and breast. Detection sensitivity was 77% on day 1 and 89% on day 2 (Table 2...Liver 8 of 10 (80%) 1 of 3 (33%) 8 of 8 (100%) Lung 5 of 5 (100%) 4 of 4 (100%) 4 of 5 (80%) Pleural effusion 2 of 2 (100%) 0 of 2 (0%) 1 of 2 (50

[Some morphometric parameters of nucleoli and nuclei in invasive ductal breast carcinomas in women].

PubMed

Karpinska-Kaczmarczyk, Katarzyna

2009-01-01

The purpose of this study was to correlate seven morphometric parameters of nucleoli and nuclei of invasive ductal cancer cells with some clinico-pathological factors such as age, tumor size, axillary lymph node status, MIB-1 proliferation index, and estrogen receptor expression in tumor cells. Methyl green-pyronin Y (MG-PY) was used for simultaneous staining of nuclei and nucleoli in histological sections of 150 invasive ductal breast carcinomas. Next, morphometric parameters of nucleoli and nuclei of tumor cells were measured with computerized image analysis. Nuclear area and number of nucleoli in breast tumor cells were greater in younger axillary node-negative patients. The number of nucleoli and nucleolar shape polymorphism were reduced in tumors measuring 20 mm or less or with lower histological grade. Nuclear area, nucleolar number, and nucleolar polymorphism in carcinomas with low proliferation index and estrogen receptor expression were smaller than in carcinomas with high proliferation index and no estrogen receptor expression. Nucleolar area in primary tumors without axillary node involvement was greater than in tumors with more than three axillary nodes positive. MG-PY selectively and simultaneously stains nucleoli and nuclei of tumor cells enabling standardized and reproducible examination of these structures with computerized image analysis. Univariate statistical analysis disclosed that some morphometric parameters of nucleoli and nuclei of tumor cells correlated with several established clinico-pathological prognostic factors. Therefore, the prognostic significance of these parameters should be studied in a larger group of patients with invasive ductal breast carcinomas.

Ethnic disparities in breast cancer between Central Europe Caucasian women of Slavic origin and Middle East Turkish subjects.

PubMed

Zubor, P; Caliskan, M; Kajo, K; Soybir, G; Topuzlu, C; Danko, J

2014-01-01

The biological, cultural, behavioral and sociodemographic differences across populations modulate breast cancer profile among races or ethnics. Following this, we aimed to identify differences in breast cancer epidemiology, histopathology, and clinical presentation from representatives of central Europe (Slovakia) and Middle-East countries (Turkey) to point on ethnic disparities in cancer biology. The population based cross-sectional study analyzing 414 cases of primary breast carcinomas where 214 represented Caucasian and 200 Turkish subjects. The differences were found for age at the time of diagnosis (<0.0001), education, menopausal status (<0.001), tumor localization (<0.01), size (<0.0001), grade (<0.05) and axillary lymph node status (<0.001) between groups. Although carcinomas in Slovak subjects were of higher grade, negative axillary nodal status was more frequent finding compared to Turkish patients (50.0 vs. 41.0%). The Slovak group showed carcinomas to be more often ER positive (72.4 vs. 54.0%; <0.001), ER/PgR positive (54.6 vs. 49.0%; <0.001), of better Nottingham prognostic index (<0.001), and less frequent Her-2 positive (21.2 vs. 28.5%). Slovak population expressed significantly higher risk of non-sentinel lymph node metastases with increased tumor size, grade, vascular invasion and Her-2 positivity compared to Turkey population. The tumor size >2 cm and high tumor grade (G3) bears a risk of OR=7.62 and OR=3.10 in Slovak compared to OR=3.94 and OR=1.79 in Turkish cases, respectively.There are wide demographic and biological disparities in breast cancer between observed ethnics providing unique information for clinicians working at the level of screening or therapy in these populations.

Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study.

PubMed

Dowsett, Mitch; Cuzick, Jack; Wale, Christopher; Forbes, John; Mallon, Elizabeth A; Salter, Janine; Quinn, Emma; Dunbier, Anita; Baum, Michael; Buzdar, Aman; Howell, Anthony; Bugarini, Roberto; Baehner, Frederick L; Shak, Steven

2010-04-10

PURPOSE To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial. PATIENTS AND METHODS RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor-positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding RS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (N0) and node-positive (N+) women. RESULTS Reportable scores were available from 1,231 evaluable patients (N0, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in N0, N+, and node status unknown patients, respectively. For both N0 and N+ patients, RS was significantly associated with time to DR in multivariate analyses (P < .001 for N0 and P = .002 for N+). RS also showed significant prognostic value beyond that provided by Adjuvant! Online (P < .001). Nine-year DR rates in low (RS < 18), intermediate (RS = 18 to 30), and high RS (RS > or = 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients. CONCLUSION This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor-positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features.

Node-Negative Breast Cancer: Which Patients Should Be Treated?

PubMed Central

Schmidt, Marcus

2008-01-01

Summary Adjuvant systemic therapy has led to markedly improved outcome in early-stage breast cancer. However, the absolute gains from chemotherapy might be modest in node-negative patients. Adjuvant chemotherapy is the only option for triple-negative breast cancer patients and should be used with trastuzumab in HER2-positive patients. Considering the large group of patients with some degree of endocrine responsiveness, adding chemotherapy according to risk is an option. At present, we guide our therapeutic decisions using clinicopathologic risk classifications like the St. Gallen risk category or Adjuvant! online. A downside of these risk estimations is a low specificity and consequently the risk for overtreatment of a considerable number of patients. To spare patients unnecessary toxicities we need more reliable prognostic factors or tumor markers. From the plethora of tumor markers, only urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor 1 (PAI-1) and certain multiparameter gene expression assays are recommended by the American Society of Clinical Oncology. These tumor markers are presently investigated in clinical trials in node-negative breast cancer (NNBC-3, MINDACT, TAILORx). These studies will hopefully allow us to quantify the risk of progression in the individual patient and to tailor treatment accordingly. This should lead to a more personalized treatment recommendation. PMID:21076603

Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer.

PubMed

Irie, Akemi; Yamauchi, Akira; Kontani, Keiichi; Kihara, Minoru; Liu, Dage; Shirato, Yukako; Seki, Masako; Nishi, Nozomu; Nakamura, Takanori; Yokomise, Hiroyasu; Hirashima, Mitsuomi

2005-04-15

Galectin-9, a member of the beta-galactoside-binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer. Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years. MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis. Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.

[Exclusive use of blue dye to detect sentinel lymph nodes in breast cancer].

PubMed

Bühler H, Simón; Rojas P, Hugo; Cayazzo M, Daniela; Cunill C, Eduardo; Vesperinas A, Gonzalo; Hamilton S, James

2008-08-01

The use of a dye and radiocolloid to detect sentinel lymph nodes in breast cancer increases the detection rates. However the use of either method alone does not modify the false negative rate. Therefore there is no formal contraindication for the exclusive use of dye to detect nodes. To report a prospective analysis of the exclusive blue dye technique for sentinel node biopsy in patients with early breast cancer. We analyzed the first 100 women with pathologically proven breast cancer who met the inclusion criteria. Patent blue dye was used as colorant. In the first 25 cases sentinel node was identified using radiocolloid and blue dye an then an axillary dissection performed. In the next 25 women, blue dye was used exclusively for detection and an axillary dissection was performed. In the next 50 cases, blue dye was used and only isolated sentinel node biopsy was performed. In 92 of the 100 women a sentinel node was successfully detected. In the first 50 women, the false negative rate of sentinel lymph node detection was 6.9%. No complications occurred. During follow-up, lasting three to 29 months, no axillary relapse was observed. Sentinel node biopsy in patients with early breast cancer using exclusively blue dye is feasible and safe.

Is a reduction in radiation lung volume and dose necessary with paclitaxel chemotherapy for node-positive breast cancer?

PubMed

Taghian, Alphonse G; Assaad, Sherif I; Niemierko, Andrzej; Floyd, Scott R; Powell, Simon N

2005-06-01

To evaluate and quantify the effect of irradiated lung volume, radiation dose, and paclitaxel chemotherapy on the development of radiation pneumonitis (RP) in breast cancer patients with positive lymph nodes. We previously reported the incidence of RP among 41 patients with breast cancer treated with radiotherapy (RT) and adjuvant paclitaxel-containing chemotherapy. We recorded the central lung distance, a measure of the extent of lung included in the RT volume, in these patients. We used this measure and the historical and observed rates of RP in our series to model the lung tolerance to RT in patients receiving chemotherapy (CHT) both with and without paclitaxel. To evaluate the risk factors for the development of RP, we performed a case-control study comparing paclitaxel-treated patients who developed RP with those who did not, and a second case-control study comparing patients receiving paclitaxel in addition to standard CHT/RT (n = 41) and controls receiving standard CHT/RT alone (n = 192). The actuarial rate of RP in the paclitaxel-treated group was 15.4% compared with 0.9% among breast cancer patients treated with RT and non-paclitaxel-containing CHT. Our mathematical model found that the effective lung tolerance for patients treated with paclitaxel was reduced by approximately 24%. No statistically significant difference was found with regard to the dose delivered to specific radiation fields, dose per fraction, central lung distance, or percentage of lung irradiated in the case-control study of paclitaxel-treated patients who developed RP compared with those who did not. In the comparison of 41 patients receiving RT and CHT with paclitaxel and 192 matched controls receiving RT and CHT without paclitaxel, the only significant differences identified were the more frequent use of a supraclavicular radiation field and a decrease in the RT lung dose among the paclitaxel-treated patients. This finding indicates that the major factor associated with development of RP was paclitaxel treatment. The use of paclitaxel chemotherapy and RT in the primary treatment of node-positive breast cancer is likely to increase the incidence of RP. In patients treated with paclitaxel, reducing the percentage of lung irradiated by 24% should reduce the risk of RP to 1%, according to our calculations of lung tolerance. Future clinical trials using combination CHT that includes paclitaxel and RT should carefully evaluate the incidence and severity of RP and should also accurately monitor the extent of lung included within the RT volume to develop safe guidelines for the delivery of what is becoming standard therapy for node-positive breast cancer.

Expression of programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO) in the tumor microenvironment and in tumor-draining lymph nodes of breast cancer.

PubMed

Ye, Qian; Wang, Chenglong; Xian, Jie; Zhang, Ming; Cao, Yijia; Cao, Youde

2018-05-01

Programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO) are both immunosuppressive proteins. Here, we investigated the relationship between PD-1 and IDO in the tumor microenvironment (TME) and in tumor-draining lymph nodes (TDLNs) in breast cancer patients. First, the protein and mRNA expression levels of PD-1 and IDO in 20 frozen tissues were examined using Western blotting and real-time polymerase chain reaction. Second, 151 paraffin-embedded breast samples and 52 lymph node samples were analyzed by immunohistochemistry. Third, correlation and survival data for PD-1 and IDO in 963 breast tumor patients were mined using the cBio Cancer Genomics Portal. We found that the protein expression level of IDO was significantly increased in frozen tumor tissues (P = .005). From paraffin-embedded samples in the TME, PD-1 + cells were only located in the stroma, while IDO was expressed in myoepithelial, stromal, and tumor cells. PD-1 and stromal IDO in the TME showed increased expression in tumors (P< .001 and P < .001, respectively). In TDLNs, PD-1 + cells were primarily located in the germinal centers (GCs), and IDO + cells were primarily located in the paracortex. Normal lymph nodes expressed PD-1 and IDO at the same level as non-metastatic and metastatic lymph nodes (P = .151 and P = .812, respectively). According to cBioPortal, the correlation analysis showed that IDO and PD-1 had high correlation coefficients (r = 0.83). These findings suggest that there is a positive correlation between the expression of PD-1 and IDO and that blocking both PD-1 and IDO pathways may represent an attractive therapeutic strategy in breast cancer treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Postmastectomy radiation therapy for lymph node-negative, locally advanced breast cancer after modified radical mastectomy: analysis of the NCI Surveillance, Epidemiology, and End Results database.

PubMed

Yu, James B; Wilson, Lynn D; Dasgupta, Tina; Castrucci, William A; Weidhaas, Joanne B

2008-07-01

The role of postmastectomy radiotherapy (PMRT) for lymph node-negative locally advanced breast carcinoma (T3N0M0) after modified radical mastectomy (MRM) with regard to improvement in survival remains an area of controversy. The 1973-2004 National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database was examined for patients with T3N0M0 ductal, lobular, or mixed ductal and lobular carcinoma of the breast who underwent MRM, treated from 1988-2003. Patients who were men, who had positive lymph nodes, who survived < or =6 months, for whom breast cancer was not the first malignancy, who had nonbeam radiation, intraoperative or preoperative radiation were excluded. The average treatment effect of PMRT on mortality was estimated with a propensity score case-matched analysis. In all, 1777 patients were identified; 568 (32%) patients received PMRT. Median tumor size was 6.3 cm. The median number of lymph nodes examined was 14 (range, 1-49). Propensity score matched case-control analysis showed no improvement in overall survival with the delivery of PMRT in this group. Older patients, patients with ER- disease (compared with ER+), and patients with high-grade tumors (compared with well differentiated) had increased mortality. The use of PMRT for T3N0M0 breast carcinoma after MRM is not associated with an increase in overall survival. It was not possible to analyze local control in this study given the limitations of the SEER database. The impact of potential improvement in local control as it relates to overall survival should be the subject of further investigation. (Copyright) 2008 American Cancer Society.

Identifying metastatic breast tumors using textural kinetic features of a contrast based habitat in DCE-MRI

NASA Astrophysics Data System (ADS)

Chaudhury, Baishali; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Drukteinis, Jennifer S.

2015-03-01

The ability to identify aggressive tumors from indolent tumors using quantitative analysis on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) would dramatically change the breast cancer treatment paradigm. With this prognostic information, patients with aggressive tumors that have the ability to spread to distant sites outside of the breast could be selected for more aggressive treatment and surveillance regimens. Conversely, patients with tumors that do not have the propensity to metastasize could be treated less aggressively, avoiding some of the morbidity associated with surgery, radiation and chemotherapy. We propose a computer aided detection framework to determine which breast cancers will metastasize to the loco-regional lymph nodes as well as which tumors will eventually go on to develop distant metastses using quantitative image analysis and radiomics. We defined a new contrast based tumor habitat and analyzed textural kinetic features from this habitat for classification purposes. The proposed tumor habitat, which we call combined-habitat, is derived from the intersection of two individual tumor sub-regions: one that exhibits rapid initial contrast uptake and the other that exhibits rapid delayed contrast washout. Hence the combined-habitat represents the tumor sub-region within which the pixels undergo both rapid initial uptake and rapid delayed washout. We analyzed a dataset of twenty-seven representative two dimensional (2D) images from volumetric DCE-MRI of breast tumors, for classification of tumors with no lymph nodes from tumors with positive number of axillary lymph nodes. For this classification an accuracy of 88.9% was achieved. Twenty of the twenty-seven patients were analyzed for classification of distant metastatic tumors from indolent cancers (tumors with no lymph nodes), for which the accuracy was 84.3%.

Factors Predictive of Sentinel Lymph Node Involvement in Primary Breast Cancer.

PubMed

Malter, Wolfram; Hellmich, Martin; Badian, Mayhar; Kirn, Verena; Mallmann, Peter; Krämer, Stefan

2018-06-01

Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in patients with early-stage breast cancer. The need for therapeutic ALND is the subject of ongoing debate especially after the publication of the ACOSOG Z0011 trial. In a retrospective trial with univariate and multivariate analyses, factors predictive of sentinel lymph node involvement should be analyzed in order to define tumor characteristics of breast cancer patients, where SLNB should not be spared to receive important indicators for adjuvant treatment decisions (e.g. thoracic wall irradiation after mastectomy with or without reconstruction). Between 2006 and 2010, 1,360 patients with primary breast cancer underwent SLNB with/without ALND with evaluation of tumor localization, multicentricity and multifocality, histological subtype, tumor size, grading, lymphovascular invasion (LVI), and estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status. These characteristics were retrospectively analyzed in univariate and multivariate logistic regression models to define significant predictive factors for sentinel lymph node involvement. The multivariate analysis demonstrated that tumor size and LVI (p<0.001) were independent predictive factors for metastatic sentinel lymph node involvement in patients with early-stage breast cancer. Because of the increased risk for metastatic involvement of axillary sentinel nodes in cases with larger breast cancer or diagnosis of LVI, patients with these breast cancer characteristics should not be spared from SLNB in a clinically node-negative situation in order to avoid false-negative results with a high potential for wrong indication of primary breast reconstruction or wrong non-indication of necessary post-mastectomy radiation therapy. The prognostic impact of avoidance of axillary staging with SLNB is analyzed in the ongoing prospective INSEMA trial. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Sentinel node detection in pre-operative axillary staging.

PubMed

Trifirò, Giuseppe; Viale, Giuseppe; Gentilini, Oreste; Travaini, Laura Lavinia; Paganelli, Giovanni

2004-06-01

The concept of sentinel lymph node biopsy in breast cancer surgery is based on the fact that the tumour drains in a logical way via the lymphatic system, from the first to upper levels. Since axillary node dissection does not improve the prognosis of patients with breast cancer, sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Subdermal or peritumoural injection of small aliquots (and very low activity) of radiotracer is preferred to intratumoural administration, and (99m)Tc-labelled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. The success rate of radioguidance in localising the sentinel lymph node in breast cancer surgery is about 97% in institutions where a high number of procedures are performed, and the success rate of lymphoscintigraphy in sentinel node detection is about 100%. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when necessary, immune staining with anti-cytokeratin antibody. Nowadays, lymphoscintigraphy is a useful procedure in patients with different clinical evidence of breast cancer.

Lymphatic Drainage to the Paravertebral Lymph Nodes in Breast Cancer Patients.

PubMed

Roman, Mirela Mariana; Barbieux, Romain; Leduc, Olivier; Bourgeois, Pierre

2017-03-01

Aberrant, altered, or blocked lymphatic drainage may contribute to the high recurrence rate of breast cancer. Thus, an efficient evaluation of lymphatic drainage from the breasts and/or upper limbs is essential in the management of lymphedema and in ipsilateral primary or contralateral recurrent breast cancer patients. There are very few reports of lymphatic drainage to the paravertebral lymph nodes in patients with a lymphedema after breast cancer surgery with or without reconstruction. We used lymphoscintigraphy to examine lymphatic drainage in a case series. We observed five patients with upper limb and/or mammary lymphedema (after breast cancer surgery with or without reconstruction) who had lymphatic drainage from the upper limb or breast to the posterior intercostal and/or paravertebral lymph nodes. One patient also presented with nodal relapse at the time of our investigation. The cases from this study demonstrate the unusual, and mostly unrecognized, lymphatic drainage pathways toward lymph nodes, which may be at risk for further evolution of breast cancer.

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2016-10-01

subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO...within the proposed time frame. 15. SUBJECT TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY...propose a randomized controlled trial to test that promise. There is compelling epidemiologic, in-vitro, and in-vivo, evidence of aspirin’s potential

Comparison of sentinel lymph node biopsy between invasive lobular carcinoma and invasive ductal carcinoma.

PubMed

Adachi, Yayoi; Sawaki, Masataka; Hattori, Masaya; Yoshimura, Akiyo; Gondo, Noami; Kotani, Haruru; Iwase, Madoka; Kataoka, Ayumi; Onishi, Sakura; Sugino, Kayoko; Terada, Mitsuo; Horisawa, Nanae; Mori, Makiko; Oze, Isao; Iwata, Hiroji

2018-03-13

Recent studies suggested that ALND (axillary lymph node dissection) can be avoided in breast cancer patients with limited SLN (sentinel lymph node) metastasis. However, these trials included only several invasive lobular carcinoma (ILC) cases, and the validity of omitting ALND for ILC remains controversial. Here, we examined whether omitting ALND is feasible in ILC treatment. A total of 3771 breast cancer patients underwent surgery for breast cancer at the Aichi Cancer Center Hospital between January 2006 and December 2015. We excluded patients with neoadjuvant therapy or without axillary management, and identified 184 ILC patients and 2402 invasive ductal carcinoma (IDC) patients. We compared SLN and non-SLN metastasis rates and the number of total ALN metastases between the ILC and IDC cohorts, and we examined the factors that influenced non-SLN metastasis in the SLN micrometastasis group. SLN biopsies were performed in 171 (93%) ILC and 2168 (90%) IDC cases, and 31 (18%) ILC and 457 (21%) IDC cases were SLN micrometastasis and macrometastasis (p = 0.36). Among SLN macrometastasis patients, 17 (68%) ILC cases and 163 (46%) IDC cases showed non-SLN metastasis (p = 0.03). The number of non-SLN metastases was greater in ILC cases compared with IDC cases. Multivariate analysis showed that ILC was the influential factor predicting non-SLN metastasis in patients with SLN macrometastasis. ILC cases had more non-SLN metastasis than IDC cases among SLN-positive cases, and ILC was an important factor for the prediction of non-SLN positivity in SLN macrometastasis cases. Omitting ALND for ILC with positive SLNs requires more consideration.

Sentinel nodes identified by computed tomography-lymphography accurately stage the axilla in patients with breast cancer

PubMed Central

2013-01-01

Background Sentinel node biopsy often results in the identification and removal of multiple nodes as sentinel nodes, although most of these nodes could be non-sentinel nodes. This study investigated whether computed tomography-lymphography (CT-LG) can distinguish sentinel nodes from non-sentinel nodes and whether sentinel nodes identified by CT-LG can accurately stage the axilla in patients with breast cancer. Methods This study included 184 patients with breast cancer and clinically negative nodes. Contrast agent was injected interstitially. The location of sentinel nodes was marked on the skin surface using a CT laser light navigator system. Lymph nodes located just under the marks were first removed as sentinel nodes. Then, all dyed nodes or all hot nodes were removed. Results The mean number of sentinel nodes identified by CT-LG was significantly lower than that of dyed and/or hot nodes removed (1.1 vs 1.8, p <0.0001). Twenty-three (12.5%) patients had ≥2 sentinel nodes identified by CT-LG removed, whereas 94 (51.1%) of patients had ≥2 dyed and/or hot nodes removed (p <0.0001). Pathological evaluation demonstrated that 47 (25.5%) of 184 patients had metastasis to at least one node. All 47 patients demonstrated metastases to at least one of the sentinel nodes identified by CT-LG. Conclusions CT-LG can distinguish sentinel nodes from non-sentinel nodes, and sentinel nodes identified by CT-LG can accurately stage the axilla in patients with breast cancer. Successful identification of sentinel nodes using CT-LG may facilitate image-based diagnosis of metastasis, possibly leading to the omission of sentinel node biopsy. PMID:24321242

Predictors for contralateral prophylactic mastectomy in breast cancer patients

PubMed Central

Fu, Yun; Zhuang, Zhigang; Dewing, Michelle; Apple, Sophia; Chang, Helena

2015-01-01

Background: In recent years, radical breast cancer surgery has been largely replaced by breast conservation treatment, due to early diagnosis and more effective adjuvant treatment. While breast conservation is mostly preferred, the trend of bilateral mastectomy has risen in the United States. The aim of this study is to determine factors influencing patients’ choice for having contralateral prophylactic mastectomy (CPM). Methods: This is a retrospective study of 373 patients diagnosed with primary invasive breast cancer who were treated by bilateral or unilateral mastectomy (BM or UM) at the Revlon/UCLA Breast Center between Jan. 2002 and Dec. 2010. In the BM group, only those with unilateral breast cancer who chose CPM were included in the analysis. Results: When compared with the UM group, the following factors were found to be associated with BM: younger age, pre-menopausal, a family history of breast/ovarian cancer, BRCA mutation, more breast biopsies, history of breast augmentation, having MRI study within 6 months before the surgery, more likely to have reconstruction and sentinel lymph node biopsy (SLNB) and fewer had neoadjuvant/adjuvant chemotherapy/radiation. When patients with bilateral breast cancer were excluded, multivariate logistic regression analysis indicated younger patients with negative nodes, SLNB as the only nodal surgery and positive family history were significant factors predicting CPM and immediate reconstruction using tissue expanders or implants. Conclusion: Younger age, lower TN stage, requiring only SLNB and high risk family history predict contralateral prophylactic mastectomy. Tissue expander/implant-based reconstructions were more frequently chosen by patients with BM. PMID:26097557

Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer.

PubMed

Dang, Chau; Guo, Hao; Najita, Julie; Yardley, Denise; Marcom, Kelly; Albain, Kathy; Rugo, Hope; Miller, Kathy; Ellis, Matthew; Shapira, Iuliana; Wolff, Antonio C; Carey, Lisa A; Moy, Beverly; Groarke, John; Moslehi, Javid; Krop, Ian; Burstein, Harold J; Hudis, Clifford; Winer, Eric P; Tolaney, Sara M

2016-01-01

Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer. To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer. In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years. Treatment consisted of weekly 80-mg/m2 doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year. Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported. Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%. Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.

Experimental Study of Magnetic Multi-Walled Carbon Nanotube-Doxorubicin Conjugate in a Lymph Node Metastatic Model of Breast Cancer.

PubMed

Ji, Jian; Liu, Minfeng; Meng, Yue; Liu, Runqi; Yan, Yan; Dong, Jianyu; Guo, Zhaoze; Ye, Changsheng

2016-07-07

BACKGROUND The lymphatic system plays a significant role in the defense of a subject against breast cancer and is one of the major pathways for the metastasis of breast cancer. To improve the prognosis, many means, including surgery, radiotherapy, and chemotherapy, have been used. However, the combination of all these modalities has limited efficacy. Lymph nodes, therefore, have become an exceptionally potential target organ in cancer chemotherapy. MATERIAL AND METHODS A lymph node metastatic model of breast cancer was established in BALB/c mice. Magnetic multi-walled carbon nanotube carrier with good adsorption and lymph node-targeting capacity was prepared and conjugated with doxorubicin to make the magnetic multi-walled carbon nanotube-doxorubicin suspension. Dispersions of doxorubicin, magnetic multi-walled carbon nanotube-doxorubicin, and magnetic multi-walled carbon nanotube were injected into lymph node metastatic mice to compare their inhibitory effects on tumor cells in vivo. Inhibition of these dispersions on EMT-6 breast cancer cells was detected via MTT assay in vitro. RESULTS Although no significant difference was found between the effects of doxorubicin and magnetic multi-walled carbon nanotube-doxorubicin with the same concentration of doxorubicin on EMT-6 breast cancer cells in vitro, in terms of sizes of metastatic lymph nodes and xenograft tumors, apoptosis in metastatic lymph nodes, and adverse reactions, the magnetic multi-walled carbon nanotube-doxorubicin group differed significantly from the other groups. CONCLUSIONS The magnetic multi-walled carbon nanotube-doxorubicin clearly played an inhibitory role in lymph node metastases to EMT-6 breast cancer cells.

The Lymphatic Anatomy of the Breast and its Implications for Sentinel Lymph Node Biopsy: A Human Cadaver Study

PubMed Central

Pan, Wei-Ren; Mann, G. Bruce; Taylor, G. Ian

2007-01-01

Background Current understanding of the lymphatic system of the breast is derived mainly from the work of the anatomist Sappey in the 1850s, with many observations made during the development and introduction of breast lymphatic mapping and sentinel node biopsy contributing to our knowledge. Methods Twenty four breasts in 14 fresh human cadavers (5 male, 9 female) were studied. Lymph vessels were identified with hydrogen peroxide and injected with a lead oxide mixture and radiographed. The specimens were cross sectioned and radiographed to provide three dimensional images. Lymph (collecting) vessels were traced from the periphery to the first-tier lymph node. Results Lymph collecting vessels were found evenly spaced at the periphery of the anterior upper torso draining radially into the axillary lymph nodes. As they reached the breast some passed over and some through the breast parenchyma, as revealed in the cross-section studies. The pathways showed no significant difference between male and female specimens. We found also perforating lymph vessels that coursed beside the branches of the internal mammary vessels, draining into the ipsilateral internal mammary lymphatics. In some studies one sentinel node in the axilla drained almost the entire breast. In most more than one sentinel node was represented. Conclusion These anatomical findings are discordant with our current knowledge based on previous studies and demand closer examination by clinicians. These anatomical studies may help explain the percentage of false-negative sentinel node biopsy studies and suggest the peritumoral injection site for accurate sentinel lymph node detection. PMID:18043970

Mammostrat as a tool to stratify breast cancer patients at risk of recurrence during endocrine therapy.

PubMed

Bartlett, John M S; Thomas, Jeremy; Ross, Douglas T; Seitz, Robert S; Ring, Brian Z; Beck, Rodney A; Pedersen, Hans Christian; Munro, Alison; Kunkler, Ian H; Campbell, Fiona M; Jack, Wilma; Kerr, Gillian R; Johnstone, Laura; Cameron, David A; Chetty, Udi

2010-01-01

Patients with early-stage breast cancer, treated with endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite endocrine therapy, additional adjuvant therapy, such as chemotherapy, may be indicated. The challenge is to prospectively identify such patients. The Mammostrat® test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions. We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up. Tissue microarrays from a consecutive series (1981 to 1998) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review. Of 1,390 cases stained, 197 received no adjuvant hormonal or chemotherapy, 1,044 received tamoxifen only, and 149 received a combination of hormonal therapy and chemotherapy. Median age at diagnosis was 57, 71% were postmenopausal, 23.9% were node-positive and median tumor size was 1.5 cm. Samples were stained using triplicate 0.6 mm2 tissue microarray cores, and positivity for p53, HTF9C, CEACAM5, NDRG1 and SLC7A5 was assessed. Each case was assigned a Mammostrat risk score, and distant recurrence-free survival (DRFS), relapse-free survival (RFS) and overall survival (OS) were analyzed by marker positivity and risk score. Increased Mammostrat scores were significantly associated with reduced DRFS, RFS and OS in estrogen receptor (ER)-positive breast cancer (P < 0.00001). In multivariate analyses the risk score was independent of conventional risk factors for DRFS, RFS and OS (P < 0.05). In node-negative, tamoxifen-treated patients, 10-year recurrence rates were 7.6 ± 1.5% in the low-risk group versus 20.0 ± 4.4% in the high-risk group. Further, exploratory analyses revealed associations with outcome in both ER-negative and untreated patients. This is the fifth independent study providing evidence that Mammostrat can act as an independent prognostic tool for ER-positive, tamoxifen-treated breast cancer. In addition, this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors. When viewed in the context of previous results, these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer.

Mammostrat® as a tool to stratify breast cancer patients at risk of recurrence during endocrine therapy

PubMed Central

2010-01-01

Introduction Patients with early-stage breast cancer, treated with endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite endocrine therapy, additional adjuvant therapy, such as chemotherapy, may be indicated. The challenge is to prospectively identify such patients. The Mammostrat® test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions. We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up. Methods Tissue microarrays from a consecutive series (1981 to 1998) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review. Of 1,390 cases stained, 197 received no adjuvant hormonal or chemotherapy, 1,044 received tamoxifen only, and 149 received a combination of hormonal therapy and chemotherapy. Median age at diagnosis was 57, 71% were postmenopausal, 23.9% were node-positive and median tumor size was 1.5 cm. Samples were stained using triplicate 0.6 mm2 tissue microarray cores, and positivity for p53, HTF9C, CEACAM5, NDRG1 and SLC7A5 was assessed. Each case was assigned a Mammostrat® risk score, and distant recurrence-free survival (DRFS), relapse-free survival (RFS) and overall survival (OS) were analyzed by marker positivity and risk score. Results Increased Mammostrat® scores were significantly associated with reduced DRFS, RFS and OS in estrogen receptor (ER)-positive breast cancer (P < 0.00001). In multivariate analyses the risk score was independent of conventional risk factors for DRFS, RFS and OS (P < 0.05). In node-negative, tamoxifen-treated patients, 10-year recurrence rates were 7.6 ± 1.5% in the low-risk group versus 20.0 ± 4.4% in the high-risk group. Further, exploratory analyses revealed associations with outcome in both ER-negative and untreated patients. Conclusions This is the fifth independent study providing evidence that Mammostrat® can act as an independent prognostic tool for ER-positive, tamoxifen-treated breast cancer. In addition, this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors. When viewed in the context of previous results, these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer. PMID:20615243

Economic evaluation of genomic test-directed chemotherapy for early-stage lymph node-positive breast cancer.

PubMed

Hall, Peter S; McCabe, Christopher; Stein, Robert C; Cameron, David

2012-01-04

Multi-parameter genomic tests identify patients with early-stage breast cancer who are likely to derive little benefit from adjuvant chemotherapy. These tests can potentially spare patients the morbidity from unnecessary chemotherapy and reduce costs. However, the costs of the test must be balanced against the health benefits and cost savings produced. This economic evaluation compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node-positive, estrogen receptor-positive early-stage breast cancer. We performed a cost-utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor-positive lymph node-positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX-selected risk groups were derived from parametric survival models fitted to data from the Southwest Oncology Group 8814 trial. The primary outcome was the incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per quality-adjusted life-year (QALY). Confidence in the incremental cost-effectiveness ratio was expressed as a probability of cost-effectiveness and was calculated using Monte Carlo simulation. Model parameters were varied deterministically and probabilistically in sensitivity analysis. Value of information analysis was used to rank priorities for further research. The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy using a recurrence score cutoff of 18 was £5529 (US $8852) per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon. The highest priority for further research identified by value of information analysis is the recurrence rate in test-selected subgroups. There is substantial uncertainty regarding the cost-effectiveness of Oncotype DX-directed chemotherapy. It is particularly important that future research studies to inform cost-effectiveness-based decisions collect long-term outcome data.

Factors affecting sentinel lymph node metastasis in Turkish breast cancer patients: Predictive value of Ki-67 and the size of lymph node.

PubMed

Ozemir, I A; Orhun, K; Eren, T; Baysal, H; Sagiroglu, J; Leblebici, M; Ceyran, A B; Alimoglu, O

We aimed to analyze the factors that affect the axillary lymph node involvement in Turkish breast cancer patients with clinically non-palpable axillary lymph node. Sentinel lymph node biopsy is the gold standard technique to evaluate the axillary lymph node status that directly influences the prognosis and the treatment options in breast cancer. Breast cancer patients without axillary lymph node involvement in clinic examination were enrolled the study. Patients were categorized into the two groups according to existence of axillary lymph node metastasis or not. Demographic, histopathological and clinical data of patients were revealed retrospectively. One-hundred and eighty-seven patients were analyzed and 101 of patients fulfilled the criteria and were included the study. Metastatic lymph node was detected in 38 (37.6 %) patients (Group 1), and was negative in 63 (62.4 %) patients (Group 2). Sentinel lymph node metastasis were statistically significant higher in patients with Ki-67 ≥ 14 % than patients with Ki-67 < 14 % (51.9 % vs 22.4 %; p < 0.01). Likewise, the mean size of the sentinel lymph node was statistically significant higher in Group 1 compared to Group 2 (p < 0.01). Ki-67 proliferation index and sentinel lymph node size may provide a higher prediction about the sentinel lymph node involvement in patients with clinically negative axillary lymph nodes (Tab. 3, Fig. 1, Ref. 31).

Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial.

PubMed

Smith, Ian; Yardley, Denise; Burris, Howard; De Boer, Richard; Amadori, Dino; McIntyre, Kristi; Ejlertsen, Bent; Gnant, Michael; Jonat, Walter; Pritchard, Kathleen I; Dowsett, Mitch; Hart, Lowell; Poggio, Susan; Comarella, Lisa; Salomon, Herve; Wamil, Barbara; O'Shaughnessy, Joyce

2017-04-01

Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) -positive and node-positive early breast cancer (eBC). Methods Postmenopausal women with HR-positive and node-positive eBC were randomly assigned to receive adjuvant therapy with either letrozole (2.5 mg) or anastrozole (1 mg) once per day for 5 years or until recurrence of disease. Patients were stratified on the basis of the number of lymph nodes and human epidermal growth factor receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709 DFS events (letrozole, 341 [16.5%]; anastrozole, 368 [17.7%]). The 5-year estimated DFS rate was 84.9% for letrozole versus 82.9% for anastrozole arm (hazard ratio, 0.93; 95% CI, 0.80 to 1.07; P = .3150). Exploratory analysis showed similar DFS with letrozole and anastrozole in all evaluated subgroups. The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most common grade 3 to 4 adverse events (> 5% of patients) reported for letrozole versus anastrozole were arthralgia (3.9% v 3.3%, and 48.2% v 47.9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive eBC.

Cryo-Assisted Resection En Bloc, and Cryoablation In Situ, of Primary Breast Cancer Coupled With Intraoperative Ultrasound-Guided Tracer Injection: A Preliminary Clinical Study.

PubMed

Korpan, Nikolai N; Xu, Kecheng; Schwarzinger, Philipp; Watanabe, Masashi; Breitenecker, Gerhard; Patrick, Le Pivert

2018-01-01

The aim of the study was to perform cryosurgery on a primary breast tumor, coupled with simultaneous peritumoral and intratumoral tracer injection of a blue dye, to evaluate lymphatic mapping. We explored the ability of our strategy to prevent tumor cells, but not that of injected tracers, to migrate to the lymphovascular drainage during conventional resection of frozen breast malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]), presenting primary breast cancer with stage I to IV, were randomly selected and treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study. Under intraoperative ultrasound, 14 patients underwent curative cryo-assisted tumor resection en bloc, coupled with peritumoral tracer injection, which consisted of complete tumor freezing and concomitant peritumor injection with a blue dye, before resection and sentinel lymph node dissection (group A). Group B consists of 3 patients previously refused any standard therapy and had palliative tumor cryoablation in situ combined with intratumoral tracer injection. The intraoperative ultrasound facilitated needle positioning and dye injection timing. In group A, the frozen site extruded the dye that was distributed through the unfrozen tumor, the breast tissue, and the resection cavity for 12 patients. One to 4 lymph nodes were stained for 10 of 14 patients. The resection margin was evaluable. Our intraoperative ultrasound-guided performance revealed the injection and migration of a blue dye during the frozen resection en bloc and cryoablation in situ of primary breast tumors. Sentinel lymph node mapping, pathological determination of the tumor, and resection margins were achievable. The study paves the way for intraoperative cryo-assisted therapeutic strategies for breast cancer.

In vivo photoacoustic and ultrasonic mapping of rat sentinel lymph nodes with a modified commercial ultrasound imaging system

NASA Astrophysics Data System (ADS)

Erpelding, Todd N.; Kim, Chulhong; Pramanik, Manojit; Guo, Zijian; Dean, John; Jankovic, Ladislav; Maslov, Konstantin; Wang, Lihong V.

2010-02-01

Sentinel lymph node biopsy (SLNB) has become the standard method for axillary staging in breast cancer patients, relying on invasive identification of sentinel lymph nodes (SLNs) following injection of blue dye and radioactive tracers. While SLNB achieves a low false negative rate (5-10%), it is an invasive procedure requiring ionizing radiation. As an alternative to SLNB, ultrasound-guided fine needle aspiration biopsy has been tested clinically. However, ultrasound alone is unable to accurately identify which lymph nodes are sentinel. Therefore, a non-ionizing and noninvasive detection method for accurate SLN mapping is needed. In this study, we successfully imaged methylene blue dye accumulation in vivo in rat axillary lymph nodes using a Phillips iU22 ultrasound imaging system adapted for photoacoustic imaging with an Nd:YAG pumped, tunable dye laser. Photoacoustic images of rat SLNs clearly identify methylene blue dye accumulation within minutes following intradermal dye injection and co-registered photoacoustic/ultrasound images illustrate lymph node position relative to surrounding anatomy. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken breast tissue on top of the rat skin surface. These results raise confidence that photoacoustic imaging can be used clinically for accurate, noninvasive SLN mapping.

Decreased Lung Perfusion After Breast/Chest Wall Irradiation: Quantitative Results From a Prospective Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liss, Adam L., E-mail: adamliss68@gmail.com; Marsh, Robin B.; Kapadia, Nirav S.

Purpose: To quantify lung perfusion changes after breast/chest wall radiation therapy (RT) using pre- and post-RT single photon emission computed tomography/computed tomography (SPECT/CT) attenuation-corrected perfusion scans; and correlate decreased perfusion with adjuvant RT dose for breast cancer in a prospective clinical trial. Methods and Materials: As part of an institutional review board–approved trial studying the impact of RT technique on lung function in node-positive breast cancer, patients received breast/chest wall and regional nodal irradiation including superior internal mammary node RT to 50 to 52.2 Gy with a boost to the tumor bed/mastectomy scar. All patients underwent quantitative SPECT/CT lung perfusion scanningmore » before RT and 1 year after RT. The SPECT/CT scans were co-registered, and the ratio of decreased perfusion after RT relative to the pre-RT perfusion scan was calculated to allow for direct comparison of SPECT/CT perfusion changes with delivered RT dose. The average ratio of decreased perfusion was calculated in 10-Gy dose increments from 0 to 60 Gy. Results: Fifty patients had complete lung SPECT/CT perfusion data available. No patient developed symptoms consistent with pulmonary toxicity. Nearly all patients demonstrated decreased perfusion in the left lung according to voxel-based analyses. The average ratio of lung perfusion deficits increased for each 10-Gy increment in radiation dose to the lung, with the largest changes in regions of lung that received 50 to 60 Gy (ratio 0.72 [95% confidence interval 0.64-0.79], P<.001) compared with the 0- to 10-Gy region. For each increase in 10 Gy to the left lung, the lung perfusion ratio decreased by 0.06 (P<.001). Conclusions: In the assessment of 50 patients with node-positive breast cancer treated with RT in a prospective clinical trial, decreased lung perfusion by SPECT/CT was demonstrated. Our study allowed for quantification of lung perfusion defects in a prospective cohort of breast cancer patients for whom attenuation-corrected SPECT/CT scans could be registered directly to RT treatment fields for precise dose estimates.« less

Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease.

PubMed

Press, M F; Pike, M C; Chazin, V R; Hung, G; Udove, J A; Markowicz, M; Danyluk, J; Godolphin, W; Sliwkowski, M; Akita, R

1993-10-15

The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced recurrent disease (relapsed cases) 105 were matched with 105 women with no recurrence (disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis.

PubMed

St Romain, Paul; Madan, Rashna; Tawfik, Ossama W; Damjanov, Ivan; Fan, Fang

2012-03-01

Prior studies have suggested that the type of breast cancer influences the location of distant metastases ("organotropism") and that there may be discordance of estrogen receptor and human epidermal growth factor receptor 2 (Her2) expression between primaries and metastases. Our aims were to investigate the relationship between tumor type and metastatic site and to compare biomarker expression between primary and metastatic tumors. We retrospectively reviewed 102 biopsy-proven cases of breast cancer metastatic to distant sites from 2000 to 2010 and 34 corresponding primaries for histologic subtype, grade, lymphovascular invasion, lymph node metastasis, and expression of estrogen receptor and Her2. Most metastases were of ductal (88) and lobular (11) histologic types. Available data on primaries indicated that the majority were grade III with positive lymph node metastasis and lymphovascular invasion. Biomarkers on 73 metastases showed 37 estrogen receptor positive/Her2-, 6 estrogen receptor positive/Her2+, 8 estrogen receptor negative/Her2+, and 22 estrogen receptor negative/Her2-. The most common metastatic sites were the lung (26%), bone (32%), and liver (21%). We found no association between estrogen receptor/Her2 profile and metastatic site (P = .16). When compared with ductal carcinoma, lobular carcinoma showed a unique metastatic pattern to gastrointestinal tract/gynecologic sites (P = .014). Of 34 cases with paired prognostic markers for primary and metastatic sites, 7 (20%) demonstrated discordance in estrogen receptor-positive/Her2 profile between the primary and the metastasis. Because the estrogen receptor-positive/Her2 profile of metastatic breast cancer did not always match that of the primary tumor, it is important to repeat the prognostic markers of metastasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Predictive Factors for Nonsentinel Lymph Node Metastasis in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy: Nomogram for Predicting Nonsentinel Lymph Node Metastasis.

PubMed

Ryu, Jai Min; Lee, Se Kyung; Kim, Ji Young; Yu, Jonghan; Kim, Seok Won; Lee, Jeong Eon; Han, Se Hwan; Jung, Yong Sik; Nam, Seok Jin

2017-11-01

Axillary lymph node (ALN) status is an important prognostic factor for breast cancer patients. With increasing numbers of patients undergoing neoadjuvant chemotherapy (NAC), issues concerning sentinel lymph node biopsy (SLNB) after NAC have emerged. We analyzed the clinicopathologic features and developed a nomogram to predict the possibility of nonsentinel lymph node (NSLN) metastases in patients with positive SLNs after NAC. A retrospective medical record review was performed of 140 patients who had had clinically positive ALNs at presentation, had a positive SLN after NAC on subsequent SLNB, and undergone axillary lymph node dissection (ALND) from 2008 to 2014. On multivariate stepwise logistic regression analysis, pathologic T stage, lymphovascular invasion, SLN metastasis size, and number of positive SLN metastases were independent predictors for NSLN metastases (P < .05). The NAC nomogram was based on these 4 variables. A receiver operating characteristic curve was plotted, and the area under the curve (AUC) was 0.791 for the NAC nomogram. In the internal validation of performance, the AUCs for the training and test sets were 0.801 and 0.760, respectively. The nomogram was validated in an external patient cohort, with an AUC of 0.705. The Samsung Medical Center NAC nomogram was developed to predict the likelihood of additional positive NSLNs. The Samsung Medical Center NAC nomogram could provide information to surgeons regarding whether to perform additional ALND when the permanent biopsy revealed positive findings, although the intraoperative SLNB findings were negative. Copyright © 2017 Elsevier Inc. All rights reserved.

10 % fluorescein sodium vs 1 % isosulfan blue in breast sentinel lymph node biopsy.

PubMed

Ren, Lidong; Liu, Zhao; Liang, Mengdi; Wang, Li; Song, Xingli; Wang, Shui

2016-11-03

Sentinel lymph node biopsy (SLNB) is well accepted to be a standard procedure in breast cancer surgery with clinically negative lymph nodes. Isosulfan blue is the first dye approved by the USA Food and Drug Administration for the localization of the lymphatic system. Few alternative tracers have been investigated. In this study, we aimed to compare the differences between 10 % fluorescein sodium and 1 % isosulfan blue in breast sentinel lymph node biopsy and to investigate the feasibility of using 10 % fluorescein sodium as a new dye for breast sentinel lymph node biopsy. A total of 30 New Zealand rabbits were randomly divided into the fluorescein sodium group and the isosulfan blue group (15 rabbits per group). Fluorescein sodium or isosulfan blue was injected subcutaneously into the second pair of mammary areolas. The average fading time of the second lymph nodes in the isosulfan blue group was significantly shorter than that in the fluorescein sodium group. Moreover, the detection rates of SLNs were higher in the fluorescein sodium group than in the isosulfan blue group. No significant differences between the fluorescein sodium group and isosulfan blue group were observed regarding the distances between the detected sentinel lymph nodes and second pair of mammary areolas, the distances between the second lymph nodes and second pair of mammary areolas, the number of detected sentinel lymph nodes and second lymph nodes, the average dyeing time of the sentinel and the second lymph nodes, and the average fading time of the second lymph nodes. In summary, we first reported that fluorescein sodium is a potential new tracer for breast sentinel lymph node biopsy.

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer

PubMed Central

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Maria Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G.; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-01-01

Around, 30–40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer. PMID:27462779

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer.

PubMed

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Mª Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-08-30

Around, 30-40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer.

Sentinel lymph node detection in breast cancer patients using surgical navigation system based on fluorescence molecular imaging technology

NASA Astrophysics Data System (ADS)

Chi, Chongwei; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Tian, Jie

2015-03-01

Introduction: Precision and personalization treatments are expected to be effective methods for early stage cancer studies. Breast cancer is a major threat to women's health and sentinel lymph node biopsy (SLNB) is an effective method to realize precision and personalized treatment for axillary lymph node (ALN) negative patients. In this study, we developed a surgical navigation system (SNS) based on optical molecular imaging technology for the precise detection of the sentinel lymph node (SLN) in breast cancer patients. This approach helps surgeons in precise positioning during surgery. Methods: The SNS was mainly based on the technology of optical molecular imaging. A novel optical path has been designed in our hardware system and a feature-matching algorithm has been devised to achieve rapid fluorescence and color image registration fusion. Ten in vivo studies of SLN detection in rabbits using indocyanine green (ICG) and blue dye were executed for system evaluation and 8 breast cancer patients accepted the combination method for therapy. Results: The detection rate of the combination method was 100% and an average of 2.6 SLNs was found in all patients. Our results showed that the method of using SNS to detect SLN has the potential to promote its application. Conclusion: The advantage of this system is the real-time tracing of lymph flow in a one-step procedure. The results demonstrated the feasibility of the system for providing accurate location and reliable treatment for surgeons. Our approach delivers valuable information and facilitates more detailed exploration for image-guided surgery research.

Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

PubMed

Evans, Andrew; Rauchhaus, Petra; Whelehan, Patsy; Thomson, Kim; Purdie, Colin A; Jordan, Lee B; Michie, Caroline O; Thompson, Alastair; Vinnicombe, Sarah

2014-01-01

Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer® ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of >150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging.

Comparison of lymphangiogenesis, lymphatic invasion, and axillary lymph node metastasis in breast carcinoma.

PubMed

Guleria, Prerna; Srinivas, V; Basannar, D; Dutta, Vibha

2018-01-01

Lymphangiogenesis correlates with poor prognosis in Invasive Ductal Carcinoma (IDC) breast. D2-40 antibody, a specific marker for lymphatic endothelium, differentiates lymphatic from vascular endothelium. Therefore, the aims of this study were to estimate lymphangiogenesis using D2-40 antibody and correlate with lymphatic invasion (LI) and axillary lymph node (LN) status and compare lymphatic mean vessel density (LMVD) with Tumor (T) and Node (N) stages and grade of tumor. The study was conducted on fifty consecutive cases of IDC breast who underwent modified radical mastectomy (MRM) from Jan 2009 to March 2011. Hematoxylin-eosin sections and Immunohistochemistry (IHC) slides were studied along with their LN status. LMVD was counted after D2-40 immunostaining (100x magnification) in three hot spots in peritumoral areas and averaged. LI as opposed to vascular invasion (BVI), and LN status for all cases were assessed. Statistical analysis was done using SPSS software (version 14.0 for Windows). Pearson's correlations, χ 2 tests and Mann-Whitney U test were used. Lymphangiogenesis varied from 0 to 58 with mean LMVD of 11. Of 50 cases, five showed no lymphatic vessels in peritumoral areas; of these five, three had positive LNs. 21/50 cases had LI. No statistical significant association was seen between lymphangiogenesis and LI. 34/50 cases had positive LNs. Mean LMVD was higher in patients with N2/N3 stage as compared to N0/N1 stage and was statistically significant (P = 0.013). D2-40 is specific marker for lymphatic endothelium. LI and lymphangiogenesis, as opposed to BVI, are better prognostic indicators in IDC breast.

New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients.

PubMed

Kohrt, Holbrook E; Olshen, Richard A; Bermas, Honnie R; Goodson, William H; Wood, Douglas J; Henry, Solomon; Rouse, Robert V; Bailey, Lisa; Philben, Vicki J; Dirbas, Frederick M; Dunn, Jocelyn J; Johnson, Denise L; Wapnir, Irene L; Carlson, Robert W; Stockdale, Frank E; Hansen, Nora M; Jeffrey, Stefanie S

2008-03-04

Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model. We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University. 285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size. We present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets.

Acoustic radiation force impulse elastography in evaluation of triple-negative breast cancer: A preliminary experience.

PubMed

Wan, Jing; Wu, Rong; Yao, Minghua; Xu, Guang; Liu, Hui; Pu, Huan; Xiang, Lihua; Zhang, Shupin

2018-05-19

To assess the elastographic features of triple-negative breast cancers and evaluate the diagnostic value of acoustic radiation force impulse imaging (ARFI) for the characterization of triple-negative breast cancers. This study analyzed data from 234 women with breast cancer. Patients were categorized into three groups; 1) triple-negative breast cancers (n = 48); 2) ER-positive tumors (n = 128) and 3) HER2-positive tumors (n = 58). Mean tumor stiffness was evaluated by virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ) and quantified as both qualitative scores (1-5) and shear wave velocity (SWV) (m/s). The relationship between mean SWV and tumor parameters, including tumor size, tumor type, histologic grade and lymph node status, were investigated using multiple linear regression. Triple-negative tumor were more likely to have a large invasive size (p = 0.002), high histological grade (p < 0.001), lymph node involvement (p = 0.022) and strong ki-67 expression (p < 0.001). The highest mean SWV value were recorded in triple-negative tumors (7.36 m/s±1.83), followed by HER2+ tumors (6.65 m/s±2.26) and ER+ tumors (6.60 m/s±2.35) (p = 0.122). Triple-negative tumors were also associated with increased stiffness than ER+ tumors and HER2+ tumors (p = 0.016), as measured by qualitative VTI scores. Tumor size was independently associated with mean SWV value on adjusted regression (p < 0.001). Triple-negative breast cancer is associated with high stiffness scores and SWV in ARFI. The latter may be considered a useful complementary tool in evaluation of triple-negative breast cancer.

[Cost-Effectiveness of the 21 Gene Assay in Patients with Node-Positive Breast Cancer].

PubMed

Fischer, L; Arnold, M; Kirsch, F; Leidl, R

2016-11-01

Aim: Breast cancer is the most common type of cancer for women. Most guidelines recommend patients with lymph-node positive (LN+) early stage breast cancer to undergo adjuvant chemotherapy to prevent or delay distant recurrence. This may lead to frequent, general usage of chemotherapy accompanied with high costs and side effects. The Oncotype DX, also called 21 Gene Assay, by Genomic Health is a genomic test which predicts the individual risk of breast cancer recurrence as well as the benefits of chemotherapy. Economic analyses have indicated the cost-effectiveness of the 21 Gene Assay for patients with LN- breast cancer. This paper discusses recent research on the cost-effectiveness of using this assay for patients with LN+ breast cancer. Methods: A systematic literature research was undertaken using the following databases: Pubmed, Embase, Business Source Complete and EconLit. Studies found were analysed for study design, parameters, and analysis of uncertainty. The transferability of the results to Germany was examined using a list of criteria. Results: 7 relevant economic analyses were identified. Incremental cost-utility ratios ranged from cost-savings of € 3 548 per patient to additional costs of € 9 113 per QALY gained. The transferability of the results to Germany is limited particularly by differences in the medical cost approach, in absolute and relative prices in health-care, and by practice variation. Conclusion: There is evidence that the cost-utility of the assay when used for LN+ breast cancer is basically comparable to that for the use with the LN- type. More precise results for Germany would require valid data on the risk of recurrence as well as on the description and evaluation of health-related quality of life of patients. © Georg Thieme Verlag KG Stuttgart · New York.

Management of the Regional Lymph Nodes Following Breast-Conservation Therapy for Early-Stage Breast Cancer: An Evolving Paradigm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Laura E.G.; Punglia, Rinaa S.; Wong, Julia S.

2014-11-15

Radiation therapy to the breast following breast conservation surgery has been the standard of care since randomized trials demonstrated equivalent survival compared to mastectomy and improved local control and survival compared to breast conservation surgery alone. Recent controversies regarding adjuvant radiation therapy have included the potential role of additional radiation to the regional lymph nodes. This review summarizes the evolution of regional nodal management focusing on 2 topics: first, the changing paradigm with regard to surgical evaluation of the axilla; second, the role for regional lymph node irradiation and optimal design of treatment fields. Contemporary data reaffirm prior studies showingmore » that complete axillary dissection may not provide additional benefit relative to sentinel lymph node biopsy in select patient populations. Preliminary data also suggest that directed nodal radiation therapy to the supraclavicular and internal mammary lymph nodes may prove beneficial; publication of several studies are awaited to confirm these results and to help define subgroups with the greatest likelihood of benefit.« less

[Pregnancy-Associated Breast Cancer: An analytical observational study].

PubMed

Baulies, Sonia; Cusidó, Maite; Tresserra, Francisco; Rodríguez, Ignacio; Ubeda, Belén; Ara, Carmen; Fábregas, Rafael

2014-03-04

Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade iii, as well as a delay in diagnosis with a higher rate of advanced stages. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Clear cell hidradenocarcinoma developing in pacemaker pocket.

PubMed

Reyes, Cesar V

2008-11-01

An octagenerian woman developed clear cell hidradenocarcinoma, a rare neoplasm of eccrine sweat gland origin, 4 years following pacemaker implantation in her right lateral chest. The tumor immunohistochemically mimicked a metastatic lobular breast carcinoma, for example, strongly positive estrogen, weakly positive progesterone, and weakly reactive mammoglobin. A complete surgical excision of the tumor was complemented with ipsilateral dissection of involved adjacent axillary lymph nodes. Recommended irradiation was refused by the patient. Retrospective 3-year mammogram review, 2-year postsurgery follow-up, and complete postmortem evaluation failed to prove a primary breast malignancy or other metastatic lesion elsewhere.

Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98.

PubMed

Loi, Sherene; Sirtaine, Nicolas; Piette, Fanny; Salgado, Roberto; Viale, Giuseppe; Van Eenoo, Françoise; Rouas, Ghizlane; Francis, Prudence; Crown, John P A; Hitre, Erika; de Azambuja, Evandro; Quinaux, Emmanuel; Di Leo, Angelo; Michiels, Stefan; Piccart, Martine J; Sotiriou, Christos

2013-03-01

Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case, anthracycline-only CT-in selected BC subtypes. We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years. There was no significant prognostic association in the global nor estrogen receptor (ER) -positive/human epidermal growth factor receptor 2 (HER2) -negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018). In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted. Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes.

Postoperative elevation of CA15-3 due to pernicious anemia in a patient without evidence of breast cancer recurrence.

PubMed

Adachi, Yayoi; Kikumori, Toyone; Miyajima, Noriyuki; Inaishi, Takahiro; Onishi, Eiji; Shibata, Masahiro; Nakanishi, Kenichi; Takeuchi, Dai; Hayashi, Hironori; Kodera, Yasuhiro

2015-12-01

Cancer antigen 15-3 (CA15-3) is considered as a marker for breast cancer recurrence. However, we encountered a case where the patient showed postoperative elevation of the CA15-3 level due to pernicious anemia without evidence of breast cancer recurrence. The patient was a 60-year-old postmenopausal woman. She had undergone partial mastectomy and sentinel lymph node biopsy (SLNB) for her T1 left breast cancer. SLNB had indicated no lymph node metastases. The tumor was positive for hormone receptors and negative for human epidermal growth factor receptor 2. Therefore, an aromatase inhibitor and external beam irradiation had been administered as adjuvant therapy. However, the CA15-3 level was found to be elevated at 6 months postoperatively. Although imaging studies did not indicate breast cancer recurrence, CA15-3 levels continued to increase. Based on the findings of blood tests and gastroendoscopy, a diagnosis of pernicious anemia due to vitamin B12 deficiency was finally confirmed at 2 years and 6 months postoperatively. The CA15-3 level returned to normal after vitamin B12 administration. The possibility of pernicious anemia should be considered in cases of postoperative elevated CA15-3 levels with no evidence of recurrence in patients with early breast cancer.

Solitary small bowel metastasis from breast cancer.

PubMed

Choi, Jung Eun; Park, Shin Young; Jeon, Myung Hoon; Kang, Su Hwan; Lee, Soo Jung; Bae, Young Kyung; Kim, Min Kyoung

2011-03-01

The common sites of metastasis of breast cancer are bone, lung, and liver, but gastrointestinal metastasis from breast cancer is rare. We experienced a case of solitary ileal metastasis from breast cancer. A 45-years-old woman presented with melena for several weeks. She showed no other abdominal symptoms. Colonoscopy findings showed an ulcerative mucosal lesion in the terminal ileum, and biopsy was performed. Pathologic examination revealed metastatic carcinoma, originated from breast. The tumor cells were positive for estrogen receptor and negative for Cdx-2. She had had a previous medical history of bilateral breast cancer and undergone breast conserving surgery with sentinel lymph node biopsy for both breasts. The torso positron emission tomography scan at 19 months after surgery showed mildly increased uptake in the terminal ileum which was considered as inflammation. Finally, she was diagnosed with solitary ileal metastasis from breast cancer at 22 months after surgery.

Expression of p53 Breast Cancer in Kurdish Women in the West of Iran: a Reverse Correlation with Lymph Node Metastasis.

PubMed

Payandeh, Mehrdad; Sadeghi, Masoud; Sadeghi, Edris; Madani, Seyed-Hamid

2016-01-01

In breast cancer (BC), it has been suggested that nuclear overexpression of p53 protein might be an indicator of poor prognosis. The aim of the current study was to evaluate the expression of p53 BC in Kurdish women from the West of Iran and its correlation with other clinicopathology figures. In the present retrospective study, 231 patients were investigated for estrogen receptor (ER) and progesterone receptor (PR) positivity, defined as ≥10% positive tumor cells with nuclear staining. A binary logistic regression model was selected using Akaike Information Criteria (AIC) in stepwise selection for determination of important factors. ER, PR, the human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%, 55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two groups: 54.5% had Ki67<20% and 45.5% had Ki67 ≥20%. Of 214 patients, 137(64%) had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion. Binary logistic regression analysis showed that there was inverse significant correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025-0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53. As in a number of studies, expression of p53 had a inverse correlation with lymph node metastasis and ER status and also a direct correlation with HER2 status. Also, p53-positivity is more likely in triple negative BC compared to other subtypes.

Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-04-01

For postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy. In the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses. In node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47-0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38-0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13-1.06), although this additional analysis was underpowered for definite conclusions. This study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isolated to patients treated with sequential endocrine therapy during the first 5 years and needs validation and long-term follow-up.

Use of trastuzumab as an adjuvant/neoadjuvant therapy in patients with HER2-positive breast cancer in China: The Nvwa study.

PubMed

Li, Junjie; Shao, Zhimin; Xu, Binghe; Jiang, Zefei; Cui, Shude; Zhang, Jin; Liao, Ning; Jiang, Jun; Wang, Yongsheng; Ouyang, Quchang; Ying, Ziwei

2018-05-01

The aim of this study was to understand current trends in trastuzumab use in China as a neoadjuvant/adjuvant therapy for human epidermal growth factor receptor-2 positive (HER2+) breast cancer and identify factors influencing trastuzumab use.This was a retrospective, multicenter, cross-sectional study of patients diagnosed with HER2+ breast cancer (stage I-III), between July 2013 and June 2014, at 155 hospitals in 29 provinces/cities in China. Demographic and clinical data, including tumor characteristics and details of adjuvant/neoadjuvant therapies used, were collected. Data analysis included univariate analysis, multivariate logistic regression, and subgroup analyses.Of 4994 HER2+ patients (mean age 51.1 ± 9.9 years) included, only 29.8% received trastuzumab, with 30.5% in adjuvant therapy and 18.3% in neoadjuvant therapy. The highest rates of adjuvant trastuzumab were in Beijing (59.3%), Jiangsu (57.1%), and Ningxia (50.0%), while those of neoadjuvant trastuzumab were in Guangdong (24.8%), Beijing (14.1%), and Zhejiang (10.7%). Multivariate regression results revealed that factors associated with trastuzumab use were medical insurance cover for trastuzumab, residing locally to the hospital, more lymph node involvement, and more advanced tumor stage. Subgroup analysis revealed that patients receiving neoadjuvant therapy were likely to be younger, premenopausal and non-local, and had lymph node metastases, more advanced tumor, and progesterone receptor positive tumor.Trastuzumab use in patients with HER2+ breast cancer is relatively low in China, especially for neoadjuvant therapy. Insurance coverage seems to be the most correlated factor that influences the use of trastuzumab in Chinese patients with HER2+ breast cancer.

The Impact of the Size of Nodal Metastases on Recurrence Risk in Breast Cancer Patients With 1-3 Positive Axillary Nodes After Mastectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Eleanor E.R., E-mail: Eleanor.harris@moffitt.org; Freilich, Jessica; Lin, Hui-Yi

Purpose: Use of postmastectomy radiation therapy (PMRT) in breast cancer patients with 1-3 positive nodes is controversial. The objective of this study was to determine whether the size of nodal metastases in this subset could predict who would benefit from PMRT. Methods and Materials: We analyzed 250 breast cancer patients with 1-3 positive nodes after mastectomy treated with contemporary surgery and systemic therapy at our institution. Of these patients, 204 did not receive PMRT and 46 did receive PMRT. Local and regional recurrence risks were stratified by the size of the largest nodal metastasis measured as less than or equalmore » to 5 mm or greater than 5 mm. Results: The median follow-up was 65.6 months. In the whole group, regional recurrences occurred in 2% of patients in whom the largest nodal metastasis measured 5 mm or less vs 6% for those with metastases measuring greater than 5 mm. For non-irradiated patients only, regional recurrence rates were 2% and 9%, respectively. Those with a maximal nodal size greater than 5 mm had a significantly higher cumulative incidence of regional recurrence (P=.013). The 5-year cumulative incidence of a regional recurrence in the non-irradiated group was 2.7% (95% confidence interval [CI], 0.7%-7.2%) for maximal metastasis size of 5 mm or less, 6.9% (95% CI, 1.7%-17.3%) for metastasis size greater than 5 mm, and 16% (95% CI, 3.4%-36.8%) for metastasis size greater than 10 mm. The impact of the maximal nodal size on regional recurrences became insignificant in the multivariable model. Conclusions: In patients with 1-3 positive lymph nodes undergoing mastectomy without radiation, nodal metastasis greater than 5 mm was associated with regional recurrence after mastectomy, but its effect was modified by other factors (such as tumor stage). The size of the largest nodal metastasis may be useful to identify high-risk patients who may benefit from radiation therapy after mastectomy.« less

Volume-Based Parameters of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Disease Recurrence Prediction in Postmastectomy Breast Cancer Patients With 1 to 3 Positive Axillary Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakajima, Naomi, E-mail: haruhi0321@gmail.com; Department of Radiology, Ehime University, Ehime; Kataoka, Masaaki

Purpose: To determine whether volume-based parameters on pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer patients treated with mastectomy without adjuvant radiation therapy are predictive of recurrence. Methods and Materials: We retrospectively analyzed 93 patients with 1 to 3 positive axillary nodes after surgery, who were studied with {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography for initial staging. We evaluated the relationship between positron emission tomography parameters, including the maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinical outcomes. Results: The median follow-up duration was 45 months. Recurrence was observed in 11 patients.more » Metabolic tumor volume and TLG were significantly related to tumor size, number of involved nodes, nodal ratio, nuclear grade, estrogen receptor (ER) status, and triple negativity (TN) (all P values were <.05). In receiver operating characteristic curve analysis, MTV and TLG showed better predictive performance than tumor size, ER status, or TN (area under the curve: 0.85, 0.86, 0.79, 0.74, and 0.74, respectively). On multivariate analysis, MTV was an independent prognostic factor of locoregional recurrence-free survival (hazard ratio 34.42, 95% confidence interval 3.94-882.71, P=.0008) and disease-free survival (DFS) (hazard ratio 13.92, 95% confidence interval 2.65-103.78, P=.0018). The 3-year DFS rate was 93.8% for the lower MTV group (<53.1; n=85) and 25.0% for the higher MTV group (≥53.1; n=8; P<.0001, log–rank test). The 3-year DFS rate for patients with both ER-positive status and MTV <53.1 was 98.2%; and for those with ER-negative status and MTV ≥53.1 it was 25.0% (P<.0001). Conclusions: Volume-based parameters improve recurrence prediction in postmastectomy breast cancer patients with 1 to 3 positive nodes. The addition of MTV to ER status or TN has potential benefits to identify a subgroup at higher risk for recurrence.« less

Patterns of metastasis and survival in breast cancer patients: a preliminary study in an Iranian population.

PubMed

Ziaei, Jamal Eivazi; Pourzand, Ali; Bayat, Amrollah; Vaez, Jalil

2012-01-01

Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software.The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone metastasis.

Impact of axillary ultrasound and core needle biopsy on the utility of intraoperative frozen section analysis and treatment decision making in women with invasive breast cancer.

PubMed

Caretta-Weyer, Holly; Sisney, Gale A; Beckman, Catherine; Burnside, Elizabeth S; Salkowsi, Lonie R; Strigel, Roberta M; Wilke, Lee G; Neuman, Heather B

2012-09-01

Our objective was to evaluate the impact of preoperative axillary ultrasound and core needle biopsy (CNB) on breast cancer treatment decision making. A secondary aim was to evaluate the impact on the utility of intraoperative sentinel lymph node (SLN) frozen section. A review of 84 patients with clinically negative axilla who underwent axillary ultrasound was performed. Sensitivity, specificity, and positive/negative predictive value for axillary ultrasound with CNB was calculated. Thirty-one (37%) had suspicious nodes. Of 27 amenable to CNB, 12 (14%) were malignant, changing treatment plans. The sensitivity of ultrasound and CNB was 54% and specificity 100%; the positive and negative predictive values were 100% and 80%, respectively. In 41 patients with normal ultrasounds who underwent SLN frozen section, 10 (24%) were positive. Preoperative axillary ultrasound impacts treatment decision making in 14%. With a sensitivity of 54%, it is a useful adjunct to, but not replacement for, SLN biopsy. Frozen section remains of utility even after a negative axillary ultrasound. Copyright © 2012 Elsevier Inc. All rights reserved.

Anatomical classification of breast sentinel lymph nodes using computed tomography-lymphography.

PubMed

Fujita, Tamaki; Miura, Hiroyuki; Seino, Hiroko; Ono, Shuichi; Nishi, Takashi; Nishimura, Akimasa; Hakamada, Kenichi; Aoki, Masahiko

2018-05-03

To evaluate the anatomical classification and location of breast sentinel lymph nodes, preoperative computed tomography-lymphography examinations were retrospectively reviewed for sentinel lymph nodes in 464 cases clinically diagnosed with node-negative breast cancer between July 2007 and June 2016. Anatomical classification was performed based on the numbers of lymphatic routes and sentinel lymph nodes, the flow direction of lymphatic routes, and the location of sentinel lymph nodes. Of the 464 cases reviewed, anatomical classification could be performed in 434 (93.5 %). The largest number of cases showed single route/single sentinel lymph node (n = 296, 68.2 %), followed by multiple routes/multiple sentinel lymph nodes (n = 59, 13.6 %), single route/multiple sentinel lymph nodes (n = 53, 12.2 %), and multiple routes/single sentinel lymph node (n = 26, 6.0 %). Classification based on the flow direction of lymphatic routes showed that 429 cases (98.8 %) had outward flow on the superficial fascia toward axillary lymph nodes, whereas classification based on the height of sentinel lymph nodes showed that 323 cases (74.4 %) belonged to the upper pectoral group of axillary lymph nodes. There was wide variation in the number of lymphatic routes and their branching patterns and in the number, location, and direction of flow of sentinel lymph nodes. It is clinically very important to preoperatively understand the anatomical morphology of lymphatic routes and sentinel lymph nodes for optimal treatment of breast cancer, and computed tomography-lymphography is suitable for this purpose.

Improvement to visualization of nodes in breast cancer patients following audit: are we seeing the problem?

PubMed

Paterson, Carolyn L; Hendry, Fraser R; Bolster, Alison A

2018-06-01

Successful localization of nodes in breast cancer patients depends upon the effectiveness of the lymphoscintigraphy technique employed. A benefit of performing imaging as part of this procedure is that it allows sites to audit their technique. An audit of breast cancer patients at the Glasgow Royal Infirmary (GRI) hospital showed nodes to be visualized in only 81% of patients. Current guidelines state that nodes should be seen in more than 95% of patients. A period of investigation and review led to changes being made to the injection and imaging technique employed at the GRI site. Following these changes a re-audit was performed that showed that the node visualization rate has successfully been increased to 97%, thereby meeting the standards set in the guidelines. This technical note details the results of the initial audit and re-audit, and explains the investigation and changes made to clinical procedures at the GRI site to improve the node visualization rate. The challenges that can occur when performing breast sentinel node procedures are also discussed.

Locoregional treatment of early breast cancer with isolated tumor cells or micrometastases on sentinel lymph node biopsy

PubMed Central

Tallet, Agnès; Lambaudie, Eric; Cohen, Monique; Minsat, Mathieu; Bannier, Marie; Resbeut, Michel; Houvenaeghel, Gilles

2016-01-01

The advent of sentinel lymph-node technique has led to a shift in lymph-node staging, due to the emergence of new entities namely micrometastases (pN1mi) and isolated tumor cells [pN0(i+)]. The prognostic significance of this low positivity in axillary lymph nodes is currently debated, as is, therefore its management. This article provides updates evidence-based medicine data to take into account for treatment decision-making in this setting, discussing the locoregional treatment in pN0(i+) and pN1mi patients (completion axillary dissection, axillary irradiation with or without regional nodes irradiation, or observation), according to systemic treatment, with the goal to help physicians in their daily practice. PMID:27081647

Intraoperative clinical assessment and pressure measurements of sentinel lymph nodes in breast cancer.

PubMed

Nathanson, S David; Shah, Rupen; Chitale, Dhananjay A; Mahan, Meredith

2014-01-01

Clinicians have long regarded firm enlarged axillary nodes as suspicious for metastasis, and this has been confirmed to represent increased pressure in sentinel lymph nodes (SLN) in vivo in breast cancer. We hypothesized that measuring intranodal pressure (INP) in the operating room would correlate with metastasis size and be more sensitive than clinical observation. Intranodal pressure mmHg was measured in SLNs #1 and #2 (N = 134 and 32) in 122 patients with T1/2 cN0 and 6 controls (T0) (8 bilateral). Clinical "Level of Suspicion" (LOS) was: 0 = benign; 1 = slightly suspicious; 2 = obvious metastasis. Statistical analysis was performed to compare INP, LOS, and SLN metastasis size mm. Sentinel lymph nodes met size correlated with INP (r = 0.65; p < 0.001). INP was 22.0 ± 1.3 mmHg in 35 SLNs with metastases compared with 9.3 ± 0.7 mmHg in 132 without (p < 0.001). Six groups created by combining LOS 0, 1, and 2 with INP >17 or ≤17 mmHg showed a significant (p < 0.001) correlation with SLN histology; sensitivity and specificity for LOS = 2/INP >17 mmHg = 100 % at predicting metastases; LOS = 0/INP ≤17 mmHg most often correct at predicting negative nodes (sensitivity 50 %, specificity 92.9 %, positive predictive value 55 %, negative predictive value 90.7 %). INP was better than LOS at predicting positive nodes in eight patients where INP was >17 mmHg. INP and LOS correlated significantly (p < 0.001). Clinical suspicion of metastasis correlated well with INP particularly at predicting macrometastases. INP was slightly better at predicting micrometastases. Measurement of INP may be valuable adjunct when performing SLN biopsy when further axillary surgery is contemplated.

Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women

PubMed Central

Chlebowski, Rowan T.; Anderson, Garnet L.; Gass, Margery; Lane, Dorothy S.; Aragaki, Aaron K.; Kuller, Lewis H.; Manson, JoAnn E.; Stefanick, Marcia L.; Ockene, Judith; Sarto, Gloria E.; MD, Karen C. Johnson; Wactawski-Wende, Jean; Ravdin, Peter M.; Schenken, Robert; Hendrix, Susan L.; Rajkovic, Aleksandar; Rohan, Thomas E.; Yasmeen, Shagufta; Prentice, Ross L.

2016-01-01

Context In the Women's Health Initiative estrogen plus progestin trial, after mean (SD) intervention of 5.6 (1.3) years (range 3.7 to 8.6 years) and mean follow-up of 7.9 (1.4) years, breast cancer incidence was increased by combined hormone therapy. However, breast cancer mortality results have not been previously reported. Objective To determine estrogen plus progestin effects on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (2.7) years thru August 14, 2009. Design, Setting, and Participants 16,608 postmenopausal women, aged 50-79 years with no prior hysterectomy, were randomly assigned to combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. After the original trial completion date (March 31, 2005) re-consent was required for continued follow-up for breast cancer incidence and was obtained in 83%. Main outcome measures Invasive breast cancer incidence and breast cancer mortality. Results In intent-to-treat analyses including all randomized participants, censoring those on March 31, 2005 not-consenting for additional follow-up, estrogen plus progestin increased invasive breast cancers compared with placebo (385 [0.42%/yr] vs 293 [0.34%/yr] cases; hazard ratio [HR] 1.25, 95% confidence interval (CI) 1.07-1.46; P=.004). The breast cancers in the estrogen plus progestin group were similar in histology and grade but were more likely to be node positive (81 [23.7%] vs 43 [16.2%], respectively; P=0.03). Deaths directly attributed to breast cancer were greater in the estrogen plus progestin group (25 [0.03%/yr] vs 12 [0.01%/yr] deaths; HR, 1.96; 95% CI 1.00-4.04, P=.049) as were deaths from all causes occurring after a breast cancer diagnosis (51 [0.05%/yr] vs 31 [0.03%/yr] deaths; HR 1.57, 95% CI 1.01-2.48; P=.045). Conclusions Estrogen plus progestin increases breast cancer incidence with cancers more commonly node positive. Breast cancer mortality also appears to be increased with combined estrogen plus progestin use. PMID:20959578

Preoperative Prediction of Node-Negative Disease After Neoadjuvant Chemotherapy in Patients Presenting with Node-Negative or Node-Positive Breast Cancer.

PubMed

Murphy, Brittany L; L Hoskin, Tanya; Heins, Courtney Day N; Habermann, Elizabeth B; Boughey, Judy C

2017-09-01

Axillary node status after neoadjuvant chemotherapy (NAC) influences the axillary surgical staging procedure as well as recommendations regarding reconstruction and radiation. Our aim was to construct a clinical preoperative prediction model to identify the likelihood of patients being node negative after NAC. Using the National Cancer Database (NCDB) from January 2010 to December 2012, we identified cT1-T4c, N0-N3 breast cancer patients treated with NAC. The effects of patient and tumor factors on pathologic node status were assessed by multivariable logistic regression separately for clinically node negative (cN0) and clinically node positive (cN+) disease, and two models were constructed. Model performance was validated in a cohort of NAC patients treated at our institution (January 2013-July 2016), and model discrimination was assessed by estimating the area under the curve (AUC). Of 16,153 NCDB patients, 6659 (41%) were cN0 and 9494 (59%) were cN+. Factors associated with pathologic nodal status and included in the models were patient age, tumor grade, biologic subtype, histology, clinical tumor category, and, in cN+ patients only, clinical nodal category. The validation dataset included 194 cN0 and 180 cN+ patients. The cN0 model demonstrated good discrimination, with an AUC of 0.73 (95% confidence interval [CI] 0.72-0.74) in the NCDB and 0.77 (95% CI 0.68-0.85) in the external validation, while the cN+ patient model AUC was 0.71 (95% CI 0.70-0.72) in the NCDB and 0.74 (95% CI 0.67-0.82) in the external validation. We constructed two models that showed good discrimination for predicting ypN0 status following NAC in cN0 and cN+ patients. These clinically useful models can guide surgical planning after NAC.

Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study.

PubMed

Solin, Lawrence J; Gray, Robert; Goldstein, Lori J; Recht, Abram; Baehner, Frederick L; Shak, Steven; Badve, Sunil; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Davidson, Nancy E; Sledge, George W; Sparano, Joseph A

2012-07-01

The present study was performed to evaluate the significance of biologic subtype and 21-gene recurrence score relative to local recurrence and local-regional recurrence after breast conservation treatment with radiation. Eastern Cooperative Oncology Group E2197 was a prospective randomized clinical trial that compared two adjuvant systemic chemotherapy regimens for patients with operable breast carcinoma with 1-3 positive lymph nodes or negative lymph nodes with tumor size >1.0 cm. The study population was a subset of 388 patients with known 21-gene recurrence score and treated with breast conservation surgery, systemic chemotherapy, and definitive radiation treatment. Median follow-up was 9.7 years (range = 3.7-11.6 years). The 10-year rates of local recurrence and local-regional recurrence were 5.4 % and 6.6 %, respectively. Neither biologic subtype nor 21-gene Recurrence Score was associated with local recurrence or local-regional recurrence on univariate or multivariate analyses (all P ≥ 0.12). The 10-year rates of local recurrence were 4.9 % for hormone receptor positive, HER2-negative tumors, 6.0 % for triple negative tumors, and 6.4 % for HER2-positive tumors (P = 0.76), and the 10-year rates of local-regional recurrence were 6.3, 6.9, and 7.2 %, respectively (P = 0.79). For hormone receptor-positive tumors, the 10-year rates of local recurrence were 3.2, 2.9, and 10.1 % for low, intermediate, and high 21-gene recurrence score, respectively (P = 0.17), and the 10-year rates of local-regional recurrence were 3.8, 5.1, and 12.0 %, respectively (P = 0.12). For hormone receptor-positive tumors, the 21-gene recurrence score evaluated as a continuous variable was significant for local-regional recurrence (hazard ratio 2.66; P = 0.03). The 10-year rates of local recurrence and local-regional recurrence were reasonably low in all subsets of patients. Neither biologic subtype nor 21-gene recurrence score should preclude breast conservation treatment with radiation.

Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study

PubMed Central

Gray, Robert; Goldstein, Lori J.; Recht, Abram; Baehner, Frederick L.; Shak, Steven; Badve, Sunil; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Sledge, George W.; Sparano, Joseph A.

2012-01-01

The present study was performed to evaluate the significance of biologic subtype and 21-gene recurrence score relative to local recurrence and local–regional recurrence after breast conservation treatment with radiation. Eastern Cooperative Oncology Group E2197 was a prospective randomized clinical trial that compared two adjuvant systemic chemotherapy regimens for patients with operable breast carcinoma with 1–3 positive lymph nodes or negative lymph nodes with tumor size >1.0 cm. The study population was a subset of 388 patients with known 21-gene recurrence score and treated with breast conservation surgery, systemic chemotherapy, and definitive radiation treatment. Median follow-up was 9.7 years (range = 3.7–11.6 years). The 10-year rates of local recurrence and local–regional recurrence were 5.4 % and 6.6 %, respectively. Neither biologic subtype nor 21-gene Recurrence Score was associated with local recurrence or local–regional recurrence on univariate or multivariate analyses (all P ≥ 0.12). The 10-year rates of local recurrence were 4.9 % for hormone receptor positive, HER2-negative tumors, 6.0 % for triple negative tumors, and 6.4 % for HER2-positive tumors (P = 0.76), and the 10-year rates of local–regional recurrence were 6.3, 6.9, and 7.2 %, respectively (P = 0.79). For hormone receptor positive tumors, the 10-year rates of local recurrence were 3.2, 2.9, and 10.1 % for low, intermediate, and high 21-gene recurrence score, respectively (P = 0.17), and the 10-year rates of local–regional recurrence were 3.8, 5.1, and 12.0 %, respectively (P = 0.12). For hormone receptor- positive tumors, the 21-gene recurrence score evaluated as a continuous variable was significant for local–regional recurrence (hazard ratio 2.66; P = 0.03). The 10-year rates of local recurrence and local–regional recurrence were reasonably low in all subsets of patients. Neither biologic subtype nor 21-gene recurrence score should preclude breast conservation treatment with radiation. PMID:22547108

The Feasibility and Oncological Safety of Axillary Reverse Mapping in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Prospective Studies

PubMed Central

Han, Chao; Yang, Ben; Zuo, Wen-Shu; Zheng, Gang; Yang, Li; Zheng, Mei-Zhu

2016-01-01

Objective The axillary reverse mapping (ARM) technique has recently been developed to prevent lymphedema by preserving the arm lymphatic drainage during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) procedures. The objective of this systematic review and meta-analysis was to evaluate the feasibility and oncological safety of ARM. Methods We searched Medline, Embase, Web of science, Scopus, and the Cochrane Library for relevant prospective studies. The identification rate of ARM nodes, the crossover rate of SLN-ARM nodes, the proportion of metastatic ARM nodes, and the incidence of complications were pooled into meta-analyses by the random-effects model. Results A total of 24 prospective studies were included into meta-analyses, of which 11 studies reported ARM during SLNB, and 18 studies reported ARM during SLNB. The overall identification rate of ARM nodes was 38.2% (95% CI 32.9%-43.8%) during SLNB and 82.8% (78.0%-86.6%) during ALND, respectively. The crossover rate of SLN-ARM nodes was 19.6% (95% CI 14.4%-26.1%). The metastatic rate of ARM nodes was 16.9% (95% CI 14.2%-20.1%). The pooled incidence of lymphedema was 4.1% (95% CI 2.9–5.9%) for patients undergoing ARM procedure. Conclusions The ARM procedure was feasible during ALND. Nevertheless, it was restricted by low identification rate of ARM nodes during SLNB. ARM was beneficial for preventing lymphedema. However, this technique should be performed with caution given the possibility of crossover SLN-ARM nodes and metastatic ARM nodes. ARM appeared to be unsuitable for patients with clinically positive breast cancer due to oncological safety concern. PMID:26919589

Patient-Reported Outcomes in Sentinel Node–Negative Adjuvant Breast Cancer Patients Receiving Sentinel-Node Biopsy or Axillary Dissection: National Surgical Adjuvant Breast and Bowel Project Phase III Protocol B-32

PubMed Central

Land, Stephanie R.; Kopec, Jacek A.; Julian, Thomas B.; Brown, Ann M.; Anderson, Stewart J.; Krag, David N.; Christian, Nicholas J.; Costantino, Joseph P.; Wolmark, Norman; Ganz, Patricia A.

2010-01-01

Purpose Sentinel lymph node resection (SNR) may reduce morbidity while providing the same clinical utility as conventional axillary dissection (AD). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 is a randomized phase III trial comparing SNR immediately followed by AD (SNAD) to SNR and subsequent AD if SN is positive. We report the definitive patient-reported outcomes (PRO) comparisons. Patients and Methods Eligible patients had clinically node-negative, operable invasive breast cancer. The PRO substudy included all SN-negative participants enrolled May 2001 to February 2004 at community institutions in the United States (n = 749; 78% age ≥ 50; 87% clinical tumor size ≤ 2.0 cm; 84% lumpectomy; 87% white). They completed questionnaires presurgery, 1 and 2 to 3 weeks postoperatively, and every 6 months through year 3. Arm symptoms, arm use avoidance, activity limitations, and quality of life (QOL) were compared with intent-to-treat two-sample t-tests and repeated measures analyses. Results Arm symptoms were significantly more bothersome for SNAD compared with SNR patients at 6 months (mean, 4.8 v 3.0; P < .001) and at 12 months (3.6 v 2.5; P = .006). Longitudinally, SNAD patients were more likely to experience ipsilateral arm and breast symptoms, restricted work and social activity, and impaired QOL (P ≤ .002 all items). From 12 to 36 months, fewer than 15% of either SNAD or SNR patients reported moderate or greater severity of any given symptom or activity limitation. Conclusion Arm morbidity was greater with SNAD than with SNR. Despite considerable fears about complications from AD for breast cancer, this study demonstrates that initial problems with either surgery resolve over time. PMID:20679600

False-negative contrast-enhanced spectral mammography: use of more than one imaging modality and application of the triple test avoids misdiagnosis.

PubMed

Taylor, Donna; O'Hanlon, Susan; Latham, Bruce

2017-03-31

A 50-year-old woman presented with chest tenderness. On examination, both breasts were lumpy. Bilateral mammography showed heterogeneously dense parenchyma, with possible stromal distortion laterally on the right at the 0900 position. On ultrasound (US), a corresponding 13×9×10 mm irregular hypoechoic mass with internal vascularity was noted and both breasts had a complex heterogeneous fibroglandular background pattern. US-guided core biopsy with marker clip insertion was performed with the diagnosis of a grade 2 invasive ductal carcinoma (IDC). In view of the parenchymal pattern on mammography and US, contrast-enhanced spectral mammography (CESM) was performed for local staging. Mild background enhancement was noted, but there was no enhancement at the lesion site. The patient elected to have bilateral mastectomies and sentinel node biopsies. Final histopathology showed a node negative 11 mm grade 2 oestrogen and progesterone receptor positive, IDC. 2017 BMJ Publishing Group Ltd.

Male breast cancer in Tripoli, Libya.

PubMed

El-Habbash, Manal M; Alwindi, Abukris A

2009-08-01

To study the epidemiology, characteristics, and survival of male breast cancer patients. This non-randomized retrospective study includes male patients with breast cancer confirmed by biopsy. A total of 1568 breast cancer patients were registered in the Oncology Department, Tripoli Medical Center, Tripoli, Libya between January 1990 to June 2008. Twenty-two patients were male (1.4%). The mean age of male breast cancer patients was 61 years. They tend to have advanced local disease, as 65% of them were tumor (T)3 and T4, and 93.3% have positive lymph nodes. The preferred surgical treatment was mastectomy and axillary clearance in 65%, and 85% had invasive duct carcinoma. Regarding hormone receptor status, 70% were estrogen and progesterone positive. A total of 71% received chemotherapy as anthracycline based. During follow up, the overall recurrence rate was 47%. The bone was the most common site of relapse (37.5%). Overall survival rate was 82.4% at first, 76.5% at second, and 57% at fifth year. Two patients were brothers, and one of them developed multiple myeloma during follow up. In comparison to female patients with breast cancer, male patients are older, and have more advanced and more hormone positive disease.

HER2-positive double primary tumor of gastric and breast cancer occur synchronously in a patient: A case report

PubMed Central

OUYANG, QUCHANG; TIAN, CAN; GAO, JIANXIANG; HUANG, JIN; FU, HUA; HE, JINSONG; YANG, JIANBO

2016-01-01

The simultaneous occurrence of primary gastric cancer and breast cancer is rare, and the positive expression of human epidermal growth factor receptor (HER)2 in double primary carcinoma of gastric and breast cancer remains to be reported. The present study presented a 46-year-old woman complaining of irregular acid reflux and stomach discomfort. The stomach cancer was diagnosed by esophagogastroduodenoscopy examination of the pathological biopsies in 2010. The patient underwent a radical gastrectomy for gastric cancer, and postoperative pathological examination revealed moderately-poorly differentiated adenocarcinoma with HER2 positive expression. The tumor invaded into the entire thickness of the gastric wall and lymph nodes. The patient received five treatments of postoperative chemotherapy. In August 2011, the patient felt a lump in the right breast. Simple excision of the right breast mass was performed on September 2011, and postoperative pathological examination revealed the invasive ductal carcinoma of the right breast with HER2 amplification by fluorescent in situ hybridization assay. The patient was treated with postoperative chemotherapy and radiotherapy, and also Trastuzumab target therapy. The patient succumbed to aggressive disease progression in March 2012. PMID:27123269

The Clinicopathological Significance of MicroRNA-155 in Breast Cancer: A Meta-Analysis

PubMed Central

Zeng, Hui; Fang, Cheng; Nam, Seungyoon; Cai, Qing; Long, Xinghua

2014-01-01

Objective. Previous studies demonstrated that the associations between expression level of microRNA-155 (miR-155) and clinicopathological significance of breast cancer remained inconsistent. Therefore, we performed a meta-analysis based on eligible studies to summarize the possible associations. Methods. We identified eligible studies published up to May 2014 by a comprehensive search of PubMed, EMBASE, CNKI, and VIP databases. The analysis was performed with RevMan. 5.0 software. Results. A total of 15 studies were included. The results of meta-analysis showed that miR-155 was positively correlated with breast cancer with standardized mean difference (SMD) = 1.22. Elevated miR-155 was found in Her-2 positive or lymph node metastasis positive, or p53 mutant type breast cancer. But the result showed to be insignificant in TNM comparison. With respect to estrogen receptor alpha (ER) and progesterone receptor (PR) status, both of them showed significant associations with SMD = −1.2 and −1.85, respectively. Conclusion. MiR-155 detection might have a diagnostic value in breast cancer patients. It might be used as an auxiliary biomarker for different clinicopathological breast cancer. PMID:25157366

The effects of ECE on the benefits of PMRT for breast cancer patients with positive axillary nodes.

PubMed

Geng, Wenwen; Zhang, Bin; Li, Danhua; Liang, Xinrui; Cao, Xunchen

2013-07-01

The purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1-3, 4-9 and ≥10 positive axillary nodes). A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as 'Radio + /ECE + ', 'Radio-/ECE + ', 'Radio + /ECE-' or 'Radio-/ECE-' according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1-3 (P = 0.5720), ≥10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4-9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). In our study, regardless of the ECE status, PMRT didn't significantly improve the LRFFS for patients with 1-3 or ≥10 positive axillary nodes. However, for patients with 4-9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.

Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Herrada, J; Iyer, R B; Atkinson, E N; Sneige, N; Buzdar, A U; Hortobagyi, G N

1997-09-01

The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph nodes. The combination of physical examination with either mammography or sonography significantly improves the accuracy of noninvasive assessment of tumor dimensions.

Diagnostic implications of a small-voxel reconstruction for loco-regional lymph node characterization in breast cancer patients using FDG-PET/CT.

PubMed

Koopman, Daniëlle; van Dalen, Jorn A; Arkies, Hester; Oostdijk, Ad H J; Francken, Anne Brecht; Bart, Jos; Slump, Cornelis H; Knollema, Siert; Jager, Pieter L

2018-01-16

We evaluated the diagnostic implications of a small-voxel reconstruction for lymph node characterization in breast cancer patients, using state-of-the-art FDG-PET/CT. We included 69 FDG-PET/CT scans from breast cancer patients. PET data were reconstructed using standard 4 × 4 × 4 mm 3 and small 2 × 2 × 2 mm 3 voxels. Two hundred thirty loco-regional lymph nodes were included, of which 209 nodes were visualised on PET/CT. All nodes were visually scored as benign or malignant, and SUV max and TB ratio (=SUV max /SUV background ) were measured. Final diagnosis was based on histological or imaging information. We determined the accuracy, sensitivity and specificity for both reconstruction methods and calculated optimal cut-off values to distinguish benign from malignant nodes. Sixty-one benign and 169 malignant lymph nodes were included. Visual evaluation accuracy was 73% (sensitivity 67%, specificity 89%) on standard-voxel images and 77% (sensitivity 78%, specificity 74%) on small-voxel images (p = 0.13). Across malignant nodes visualised on PET/CT, the small-voxel score was more often correct compared with the standard-voxel score (89 vs. 76%, p <  0.001). In benign nodes, the standard-voxel score was more often correct (89 vs. 74%, p = 0.04). Quantitative data were based on the 61 benign and 148 malignant lymph nodes visualised on PET/CT. SUVs and TB ratio were on average 3.0 and 1.6 times higher in malignant nodes compared to those in benign nodes (p <  0.001), on standard- and small-voxel PET images respectively. Small-voxel PET showed average increases in SUV max and TB ratio of typically 40% over standard-voxel PET. The optimal SUV max cut-off using standard-voxels was 1.8 (sensitivity 81%, specificity 95%, accuracy 85%) while for small-voxels, the optimal SUV max cut-off was 2.6 (sensitivity 78%, specificity 98%, accuracy 84%). Differences in accuracy were non-significant. Small-voxel PET/CT improves the sensitivity of visual lymph node characterization and provides a higher detection rate of malignant lymph nodes. However, small-voxel PET/CT also introduced more false-positive results in benign nodes. Across all nodes, differences in accuracy were non-significant. Quantitatively, small-voxel images require higher cut-off values. Readers have to adapt their reference standards.

Impact of pathologic diagnosis of internal mammary lymph node metastasis in clinical N2b and N3b breast cancer patients.

PubMed

Joo, Ji Hyeon; Kim, Su Ssan; Ahn, Seung-Do; Choi, Eun Kyung; Jung, Jin Hong; Jeong, Yuri; Ahn, Sei Hyun; Son, Byung Ho; Lee, Jong Won; Kim, Hee Jung; Go, Beom Seok; Kim, Hak Hee; Cha, Joo Hee; Shin, Hee Jung; Chae, Eun Young

2017-11-01

To analyze the prognostic role of pathologic confirmation of internal mammary lymph nodes (IMNs) for breast cancer patients who received neoadjuvant chemotherapy. Of the patients who were treated with neoadjuvant chemotherapy, surgery, and radiation therapy between 2009 and 2013, 114 women had suspicious IMNs and FNAB was attempted. Clinical IMN metastasis was diagnosed by 18F-FDG PET/CT positivity or pathologic confirmation (N = 70). Patients were divided into the FNAB(+) or FNAB(-) IMN group. The pathologic confirmation rate was 57% (40 of 70 patients). Rates were 74% in US-positive, 70% in MRI-positive, and 55% in PET-positive patients. Nodal stage was cN2b (6%) or cN3b (94%). Five-year progression-free survival (PFS) was significantly worse in patients with FNAB(+) IMN metastasis than FNAB(-) IMN metastasis (61% vs. 87%, P = 0.03). FNAB(+) IMN patients showed worse distant metastasis and regional recurrence-free survival without statistical significance (69% vs. 86%, P = 0.06, and 81% vs. 96%, P = 0.06). With median follow-up of 50.5 months (13.0-97.0 months), overall survival at 5 years was 77%, and PFS was 72%. Patients with FNAB-proven IMN metastasis had worse treatment outcomes compared to patients with clinically diagnosed IMN metastasis in cN2b/N3b breast cancer.

SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer

PubMed Central

Wang, Chu-An; Jedlicka, Paul; Patrick, Aaron N.; Micalizzi, Douglas S.; Lemmer, Kimberly C.; Deitsch, Erin; Casás-Selves, Matias; Harrell, J. Chuck; Ford, Heide L.

2012-01-01

An association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago. However, the mechanisms by which tumor cells infiltrate the lymphatic system are not completely understood. Recently, it has been proposed that the lymphatic system has an active role in metastatic dissemination and that tumor-secreted growth factors stimulate lymphangiogenesis. We therefore investigated whether SIX1, a homeodomain-containing transcription factor previously associated in breast cancer with lymph node positivity, was involved in lymphangiogenesis and lymphatic metastasis. In a model in which human breast cancer cells were injected into immune-compromised mice, we found that SIX1 expression promoted peritumoral and intratumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. SIX1 induced transcription of the prolymphangiogenic factor VEGF-C, and this was required for lymphangiogenesis and lymphatic metastasis. Using a mouse mammary carcinoma model, we found that VEGF-C was not sufficient to mediate all the metastatic effects of SIX1, indicating that SIX1 acts through additional, VEGF-C–independent pathways. Finally, we verified the clinical significance of this prometastatic SIX1/VEGF-C axis by demonstrating coexpression of SIX1 and VEGF-C in human breast cancer. These data define a critical role for SIX1 in lymphatic dissemination of breast cancer cells, providing a direct mechanistic explanation for how VEGF-C expression is upregulated in breast cancer, resulting in lymphangiogenesis and metastasis. PMID:22466647

Sentinel node biopsy performance after neoadjuvant chemotherapy in locally advanced breast cancer: A systematic review and meta-analysis.

PubMed

Mocellin, Simone; Goldin, Elena; Marchet, Alberto; Nitti, Donato

2016-01-15

The use of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is debated. Our aim was to quantitatively review the available evidence on the performance of SNB after NAC in patients with locally advanced breast cancer. We performed a systematic review (by searching the PubMed, Cochrane and Scopus databases) and random effects meta-analysis to investigate on the feasibility and accuracy of SNB in these patients. The two outcomes of interest were the sentinel node identification rate (SIR) and the false negative rate (FNR). Sensitivity analysis and meta-regression were used to investigate the potential sources of between-study heterogeneity. We retrieved 72 eligible studies enrolling 7,451 patients. Upon meta-analysis, summary SIR resulted 89.6% [95% confidence interval (CI): 87.8-91.2; heterogeneity I(2): 76.9%], which poorly compares with the 95% SIR observed in some recent series of early breast cancer. The summary FNR resulted 14.2% (CI: 12.5-16.0; heterogeneity I(2): 29.1%), which was significantly higher than the 8-10% reference value. Considering an average post-NAC lymph node positivity rate of 50%, the downstaging due to false negative SNB would occur in 7/100 patients (with an excess error rate of 2-3/100 as compared to the early-stage setting). No plausible source of between-study heterogeneity was found. Based on the largest series of studies ever meta-analyzed, our findings highlight the limits of SNB performance in this population, where the impact of SNB on patient survival is still to be defined. © 2015 UICC.

Determining Which Patients Require Irradiation of the Supraclavicular Nodal Area After Surgery for N1 Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Jeong Il; Park, Won, E-mail: wonp68@skku.ed; Huh, Seung Jae

2010-11-15

Purpose: We designed this study to determine which patients have a high risk of supraclavicular node recurrence in N1 breast cancer previously treated with surgery but not having received supraclavicular radiation therapy (SCRT) and to identify which patients needed SCRT. Methods and Materials: We performed a retrospective review of 448 pathologic N1 breast cancer patients treated with mastectomy or breast-conserving treatment, but without SCRT, between 1994 and 2003. Mastectomy was performed in 302 patients (67.4%). The median number of axillary nodes dissected was 17 (range, 5-53). Systemic chemotherapy was administered in 443 patients (98.9%), and 144 patients received radiation aftermore » breast-conserving surgery. The median follow-up was 88 months (range, 15-170 months). Results: At follow-up, the treatment failed in 101 patients (22.5%), and 39 patients (8.7%) had supraclavicular node recurrence. Prognostic factors in supraclavicular node recurrence included lymphovascular invasion (p < 0.0001), extracapsular extension (p < 0.0001), the number of involved axillary nodes (p = 0.0003), and the level of involved axillary nodes (p = 0.012) in univariate and multivariate analyses. The total number of prognostic factors correlated well with supraclavicular node recurrence. In the analysis of 5-year supraclavicular node recurrence-free survival, patients with two or more factors showed a significantly higher recurrence rate than did patients with fewer than two factors (96.8% and 72.9%, respectively; p < 0.0001). Conclusions: The prognostic factors associated with supraclavicular node recurrence were lymphovascular invasion, extracapsular extension, and the number and level of involved axillary nodes. Patients with two or more prognostic factors might benefit from SCRT.« less

Concordance between peri-areolar blue dye and peri-incisional radiotracer injections for sentinel node mapping in patients with a history of primary breast cancer excisonal biopsy.

PubMed

Mehrabibahar, M; Azizi, S; Jangjoo, A; Saremi, E; Kakhki, V R Dabbagh; Sadeghi, R; Chicken, D W; Keshtgar, M

2014-01-01

We evaluated the concordance between peri-areolar blue dye and peri-incisional radiotracer injections for axillary sentinel node mapping of patients with the history of previous breast lesion excisional biopsy. 80 patients with the history of previous excisional biopsy of the breast lesions were included. All patients received two injections of 99mTc-antimony sulfide colloid in both ends of incision line in an intradermal fashion. 2 mL patient blue V dye was injection to all patients in the peri-areolar area of the index quadrant after induction of anesthesia. All blue or hot nodes were harvested as sentinel lymph nodes. At least one sentinel node could be detected during surgery in 79 patients. In total 94 sentinel nodes were detected. All detected sentinel nodes were hot. In three patients sentinel nodes were detected by gamma probe but not blue dye. The tumor location in all of these patients was in the upper lateral quadrant and the incision line was extended into the axillary tail of the breast in all of them. 91 out of 94 sentinel nodes were stained blue, which amounts to 95.8% concordance between blue dye and radiotracer on a per node analysis. Single peri-areolar injection in the index quadrant would suffice for sentinel node mapping of patients with history of excisional biopsy. Care should be taken in patients with large excisional biopsy in the extreme proximity to axilla.

21-Gene recurrence score and locoregional recurrence in lymph node-negative, estrogen receptor-positive breast cancer

PubMed Central

Turashvili, Gulisa; Chou, Joanne F.; Brogi, Edi; Morrow, Monica; Dickler, Maura; Norton, Larry; Hudis, Clifford; Wen, Hannah Y

2017-01-01

Background/purpose The 21-gene recurrence score (RS) assay evaluates the likelihood of distant recurrence and benefit of chemotherapy in lymph node-negative, estrogen receptor (ER)-positive, HER2-negative breast cancer patients. The RS categories are associated with the risk of locoregional recurrence (LRR) in some, but not all studies. Methods We reviewed the institutional database to identify consecutive female patients with node-negative, ER+/HER2− breast carcinoma tested for the 21-gene RS assay and treated at our center from 2008 to 2013. We collected data on clinicopathologic features, treatment, and outcome. Statistical analysis was performed using SAS version 9.4 or R version 3.3.2. Results Of 2326 patients, 60% (1394) were in the low RS group, 33.4% (777) in the intermediate RS group, and 6.6% (155) in the high RS group. Median follow-up was 53 months. A total of 44 LRRs were observed, with a cumulative incidence of 0.17% at 12 months and 1.6% at 48 months. The cumulative incidence of LRR at 48 months was 0.84%, 2.72% and 2.80% for low, intermediate, and high RS groups, respectively (p<0.01). Univariate analysis showed that the risk of LRR was associated with the RS categories (p<0.01), T stage (p<0.01) and lymphovascular invasion (LVI) (p=0.009). There was no difference in LRR rates by initial local treatment (total mastectomy vs. breast-conserving surgery plus radiation therapy). The RS remained significantly associated with LRR after adjusting for LVI and T stage. Compared to patients with low RS, the risk of LRR was increased more than 4-fold (hazard ratio: 4.61, 95% CI 1.90–11.19, p<0.01), and 3-fold (hazard ratio: 2.81, 95% CI 1.41–5.56, p<0.01) for high and intermediate risk categories, respectively. Conclusions Our study confirms that RS is significantly associated with the risk of LRR in node-negative, ER+/HER2− breast cancer patients. Our findings suggest that in addition to its value for prognostic stage grouping and decision-making regarding adjuvant systemic therapy, the role of the RS in identifying patients not requiring radiotherapy should be studied. PMID:28702894

Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy.

PubMed

Esteva, Francisco J; Sahin, Aysegul A; Cristofanilli, Massimo; Coombes, Kevin; Lee, Sang-Joon; Baker, Joffre; Cronin, Maureen; Walker, Michael; Watson, Drew; Shak, Steven; Hortobagyi, Gabriel N

2005-05-01

To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based on gene expression profiles, to accurately determine the risk of recurrence in patients with node-negative breast cancer who did not receive systemic therapy using formalin-fixed, paraffin-embedded tissue. A secondary objective was to determine whether the quantitative RT-PCR data correlated with immunohistochemistry assay data regarding estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We obtained archival paraffin-embedded tissue from patients with invasive breast cancer but no axillary lymph node involvement who had received no adjuvant systemic therapy and been followed for at least 5 years. RNA was extracted from three 10-microm-thick sections. The expression of 16 cancer-related genes and 5 reference genes was quantified using RT-PCR. A gene expression algorithm was used to calculate a recurrence score for each patient. We then assessed the ability of the test to accurately predict distant recurrence-free survival in this population. We identified 149 eligible patients. Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year disease-free survival rate for the group was 80%. The 21 gene-based recurrence score was not predictive of distant disease recurrence. However, a high concordance between RT-PCR and immunohistochemical assays for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status was noted. RT-PCR can be done on paraffin-embedded tissue to validate the large numbers of genes associated with breast cancer recurrence. However, further work needs to be done to develop an assay to identify the likelihood of recurrent disease in patients with node-negative breast cancer who do not receive adjuvant tamoxifen or chemotherapy.

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

PubMed

Zdenkowski, N; Forbes, J F; Boyle, F M; Kannourakis, G; Gill, P G; Bayliss, E; Saunders, C; Della-Fiorentina, S; Kling, N; Campbell, I; Mann, G B; Coates, A S; Gebski, V; Davies, L; Thornton, R; Reaby, L; Cuzick, J; Green, M

2016-05-01

Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Chemotherapy of nonelderly breast cancer patients by poverty-rate of area of residence in Connecticut.

PubMed

Polednak, Anthony P

2004-02-01

For 684 nonelderly Connecticut women diagnosed in 1999 with early-stage breast cancer, routinely reported information on chemotherapy in a population-based cancer registry was supplemented by questionnaires to their physicians. Receipt of or recommendation for chemotherapy was associated with younger age, larger tumor size and positive lymph-node status, but not with higher poverty-rate (upper quintile) of census tract of residence at diagnosis. Similar studies are needed in other geographical areas that differ in socioeconomic indicators.

Center for the Evaluation of Biomarkers for the Early Detection of Breast Cancer

DTIC Science & Technology

2009-10-01

Table S1, including mammography (BI-RADS) score and breast density at the last mammogram before diagnosis, lymph node positivity, tumor size, number of...Bibliography 1.& Fletcher RH. Should all people over the age of 50 have regular fecal occult-blood tests? If it works, why not do it? New England Journal...blocked for 15 minutes at room temperature in fluores- cence-activated cell sorting (FACS) buffer (PBS, 0.1% bovine serum albumin (BSA), 0.02% sodium

Invasive mucinous (colloid) adenocarcinoma of ectopic breast tissue in the vulva: a case report.

PubMed

Yin, C; Chapman, J; Tawfik, O

2003-01-01

We present the first case of primary vulvar mucinous adenocarcinoma of ectopic breast origin. The patient is an 84-year-old woman with a mass on the left side of her vulva. A left partial vulvectomy with bilateral inguinal lymph node dissections revealed a mucinous adenocarcinoma that involved the dermis and subcutaneous tissue. The tumor cells were positive for estrogen receptors (ERs), progesterone receptors (PRs), and BRST-1 markers. The clinical and pathologic features, differential diagnosis, and treatment are discussed.

Breast cancer lymphoscintigraphy: Factors associated with sentinel lymph node non visualization.

PubMed

Vaz, S C; Silva, Â; Sousa, R; Ferreira, T C; Esteves, S; Carvalho, I P; Ratão, P; Daniel, A; Salgado, L

2015-01-01

To evaluate factors associated with non identification of the sentinel lymph node (SLN) in lymphoscintigraphy of breast cancer patients and analyze the relationship with SLN metastases. A single-center, cross-sectional and retrospective study was performed. Forty patients with lymphoscintigraphy without sentinel lymph node identification (negative lymphoscintigraphy - NL) were enrolled. The control group included 184 patients with SLN identification (positive lymphoscintigraphy - PL). Evaluated factors were age, body mass index (BMI), tumor size, histology, localization, preoperative breast lesion hookwire (harpoon) marking and SLN metastases. The statistical analysis was performed with uni- and multivariate logistic regression models and matched-pairs analysis. Age (p=0.036) or having BMI (p=0.047) were the only factors significantly associated with NL. Being ≥60 years with a BMI ≥30 increased the odds of having a NL 2 and 3.8 times, respectively. Marking with hookwire seems to increase the likelihood of NL, but demonstrated statistical significance is lacking (p=0.087). The other tested variables did not affect the examination result. When controlling for age, BMI and marking with the harpoon, a significant association between lymph node metastization and NL was not found (p=0.565). The most important factors related with non identification of SLN in the patients were age, BMI and marking with hook wire. However, only the first two had statistical importance. When these variables were controlled, no association was found between NL and axillary metastases. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Sentinel node biopsy and concomitant probe-guided tumor excision of nonpalpable breast cancer.

PubMed

van Rijk, Maartje C; Tanis, Pieter J; Nieweg, Omgo E; Loo, Claudette E; Olmos, Renato A Valdés; Oldenburg, Hester S A; Rutgers, Emiel J Th; Hoefnagel, Cornelis A; Kroon, Bin B R

2007-02-01

Preliminary data have shown encouraging results of a single intratumoral radiopharmaceutical injection that enables both sentinel node biopsy and probe-guided excision of the primary tumor in patients with nonpalpable breast cancer. The aim of the study was to evaluate this approach in a large group of patients. Lymphoscintigraphy was performed in 368 patients with nonpalpable breast cancer after intratumoral injection of (99m)Tc-nanocolloid (.2 mL, 123 MBq, 3.3 mCi) guided by ultrasound or stereotaxis. The sentinel node was pursued with the aid of vital blue dye (1.0 mL, intratumoral) and a gamma ray detection probe. In case of breast-conserving surgery, the probe was used to guide the excision. At least one sentinel node could be identified intraoperatively in 357 patients (97%), of whom 69 had involved nodes (19%). Age over 60 years was associated with less frequent nonaxillary lymphatic drainage and absence of internal mammary chain dissemination. Tumor-free margins were obtained in 262 (89%) of the 293 patients who underwent segmental excision. Re-excision of the primary tumor bed was performed in six patients (2%). During a median follow-up of 22 months, one breast recurrence and one axillary recurrence were observed. Lymphatic mapping and probe-guided tumor excision of nonpalpable breast cancer by intralesional administration of a single dose of (99m)Tc-nanocolloid and blue dye resulted in 97% identification of the sentinel node and in tumor-free margins in 89% of the patients who underwent breast-conserving surgery. Longer follow-up is needed to substantiate the accuracy and safety of this technique.

Isolated adenocarcinoma of the nipple

PubMed Central

Ahmed, M; Basit, A

2011-01-01

A 47-year-old female presented with a 1-year history of ‘eczematous change’ to the right nipple. Bilateral mammography and ultrasound were entirely normal. Free hand biopsy demonstrated invasive adenocarcinoma of the nipple. The patient underwent a right-sided central segmentectomy and sentinel node biopsy. Histology demonstrated that the nipple was almost completely replaced by an invasive ductal carcinoma with a maximum diameter of 13 mm. Invasion of the underlying breast tissue was to a depth of 3 mm. A single sentinel lymph node demonstrated metastatic carcinoma. Her oestrogen receptor status was positive while HER-2 status was negative. The patient subsequently underwent right-sided axillary node clearance to level three nodes. All 17 nodes in the specimen were found to be within normal limits. She is scheduled to undergo radiotherapy, chemotherapy and hormonal treatment. PMID:22689722

Tracking Nonpalpable Breast Cancer for Breast-conserving Surgery With Carbon Nanoparticles

PubMed Central

Jiang, Yanyan; Lin, Nan; Huang, Sheng; Lin, Chongping; Jin, Na; Zhang, Zaizhong; Ke, Jun; Yu, Yinghao; Zhu, Jianping; Wang, Yu

2015-01-01

Abstract To examine the feasibility of using carbon nanoparticles to track nonpalpable breast cancer for breast-conserving surgery. During breast-conserving surgery, it is often very challenging to determine the boundary of tumor and identify involved lymph nodes. Currently used methods are useful in identifying tumor location, but do not provide direct visual guidance for resection margin during surgery. The study was approved by the Institutional Review Board of the Fuzhou General Hospital (Fuzhou, China). The current retrospective analysis included 16 patients with nonpalpable breast cancer receiving breast-conserving surgery under the guidance of preoperative marking using a carbon nanoparticle, as well as 3 patients receiving carbon nanoparticle marking followed by neoadjuvant treatment and then breast-conserving surgery. The Tumor Node Metastasis stage in the 16 cases included: T1N0M0 in 7, T1N1M0 in 2, T2N0M0 in 4, and T2N1M0 in the remaining 3 cases. The nanoparticle was injected at 12 sites at 0.5 cm away from the apparent edge under colored ultrasonography along 6 tracks separated by 60 degrees (2 sites every track). Lymph node status was also examined. The resection edge was free from cancer cells in all 16 cases (and the 3 cases with neoadjuvant treatment). Cancer cells were identified in majority of stained lymph nodes, but not in any of the unstained lymph nodes. No recurrence or metastasis was noticed after the surgery (2 to 22-month follow-up; median: 6 months). Tracking nonpalpable breast cancer with carbon nanoparticle could guide breast-conserving surgery. PMID:25761181

Financial aspects of sentinel lymph node biopsy in early breast cancer.

PubMed

Severi, S; Gazzoni, E; Pellegrini, A; Sansovini, M; Raulli, G; Corbelli, C; Altini, M; Paganelli, G

2012-02-01

At present, early breast cancer is treated with conservative surgery of the primary lesion (BCS) along with axillary staging by sentinel lymph node biopsy (SLNB). Although the scintigraphic method is standardized, its surgical application is different for patient compliance, work organization, costs, and diagnosis related group (DRG) reimbursements. We compared four surgical protocols presently used in our region: (A) traditional BCS with axillary lymph node dissection (ALND); (B) BCS with SLNB and concomitant ALND for positive sentinel nodes (SN); (C) BCS and SLNB under local anaesthesia with subsequent ALND under general anaesthesia according to the SN result; (D) SLNB under local anaesthesia with subsequent BCS under local anaesthesia for negative SN, or ALND under general anaesthesia for positive SN. For each protocol, patient compliance, use of consumables, resources and time spent by various dedicated professionals, were analyzed. Furthermore, a detailed breakdown of 1-/2-day hospitalization costs was calculated using specific DRGs. We reported a mean costs variation that ranged from 1,634 to 2,221 Euros (protocols C and D). The number of procedures performed and the pathologists' results are the most significant variables affecting the rate of DRG reimbursements, that were the highest for protocol D and the lowest for protocol B. In our experience protocol C is the most suitable in terms of patient compliance, impact of surgical procedures, and work organization, and is granted by an appropriate DRG. We observed that a multidisciplinary approach enhances overall patient care and that a revaluation of DRG reimbursements is opportune.

Primary peritoneal serous carcinoma presenting as inflammatory breast cancer.

PubMed

Khalifeh, Ibrahim; Deavers, Michael T; Cristofanilli, Massimo; Coleman, Robert L; Malpica, Anais; Gilcrease, Michael Z

2009-01-01

Metastasis to the breast from extramammary malignancies is rare. Nevertheless, its recognition is important because the prognosis and treatment differ from that of primary breast cancer. We report a unique case of primary peritoneal serous carcinoma that initially presented as inflammatory breast cancer. The patient received neoadjuvant chemotherapy for breast cancer and subsequently underwent bilateral total mastectomy and bilateral sentinel lymph node biopsy. She was found to have extensive intralymphatic carcinoma in both breasts, with only focal minimal breast parenchymal involvement, and residual metastatic carcinoma in bilateral sentinel lymph nodes. Further work-up revealed pelvic ascites and omental nodularities. The patient underwent laparoscopic bilateral salpingo-oophorectomy, which revealed high-grade serous carcinoma involving both ovaries and fallopian tubes. Molecular testing of tumor from the ovary and axillary lymph node showed an identical pattern of allelic loss, confirming a common origin for both tumors. To our knowledge, this is the first reported case of an extramammary primary malignancy that not only presented as inflammatory breast cancer but also was diagnosed and initially treated as such.

Prediction of margin involvement and local recurrence after skin-sparing and simple mastectomy.

PubMed

Al-Himdani, S; Timbrell, S; Tan, K T; Morris, J; Bundred, N J

2016-07-01

Skin-sparing mastectomy (SSM) facilitates immediate breast reconstruction. We investigated locoregional recurrence rates after SSM compared with simple mastectomy and the factors predicting oncological failure. Patients with early breast cancer that underwent mastectomy between 2000 and 2005 at a single institution were studied to ascertain local and systemic recurrence rates between groups. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival. Patients (n = 577) underwent simple mastectomy (80%) or SSM (20%). Median follow up was 80 months. Patients undergoing SSM were of younger average age, less often had involved lymph nodes (22% vs 44%, p < 0.001), more often had DCIS present (79% vs 53%, p < 0.001) and involved margins (29% vs 15%, p = 0.001). Involved surgical margins were associated with large size (p = 0.001). The 8-year local recurrence (LR) rates were 7.9% for SSM and 5% for simple mastectomy respectively (p = 0.35). Predictors of locoregional recurrence were lymph node involvement (HR 8.0, for >4 nodes, p < 0.001) and involved surgical margins (HR 3.3, p = 0.002). In node negative patients, SSM was a predictor of locoregional recurrence (HR 4.8 [1.1, 19.9], p = 0.033). Delayed reconstruction is more appropriate for node positive early breast cancer after post-mastectomy radiotherapy. Re-excision of involved margins is essential to prevent local recurrence after mastectomy. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Small breast cancers: when and how to treat.

PubMed

Tryfonidis, K; Zardavas, D; Cardoso, F

2014-12-01

Small (T1a, b), lymph node negative breast tumors represent an entity diagnosed with increasing frequency due to the implementation of wide-scale screening programs. Patients bearing such tumors usually exhibit favorable long-term outcomes, with low breast cancer mortality rates at 10years, even in the absence of adjuvant chemotherapy. However, most available data derive from retrospective studies. Additionally, a subset of patients with these tumors experience recurrence of the disease, indicating that early tumor stage itself is not a sufficient prognosticator. It is of paramount importance to refine the prognosis of this population, identifying patients with high risk of recurrence, for whom adjuvant treatment is needed. The underlying biology of the disease provides relevant information, such as grade and status of hormone receptors and HER-2 (human epidermal growth factor receptor 2), with high grade, triple negative and HER-2-positive tumors having worse prognosis. Additionally, multigene signatures may improve further the prognostication of patients with small, node negative breast cancers. Further research for this increasingly frequent group of patients is urgently needed, so that better informed clinical decision making, in particular regarding adjuvant chemotherapy, can occur. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stereotactic Magnetic Resonance-guided Online Adaptive Radiotherapy for Oligometastatic Breast Cancer: A Case Report

PubMed Central

Cao, Minsong; Raldow, Ann C; Dang, Audrey; Lamb, James; Low, Daniel A; Steinberg, Michael L.; Lee, Percy

2018-01-01

We present a case of durable local control achieved in a patient treated with stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for an abdominal lymph node in the setting of oligometastatic breast cancer. A 50-year-old woman with a history of triple positive metastatic invasive ductal carcinoma of the left breast, stage IV (T3N2M1), underwent neoadjuvant chemotherapy, mastectomy, adjuvant radiotherapy and maintenance hormonal treatment with HER2 targeted therapies. At 20 months after definitive treatment of her primary, imaging showed an isolated progressive enlargement of lymph nodes between hepatic segment V/IVB and the neck of the pancreas. Radiofrequency ablation was considered, however, this approach was decided not to be optimal due to the proximity to stomach, and pancreatic duct. The patient was treated with SMART for 40 Gray in 5 fractions. Two and a half years later, the patient remains without evidence of disease progression. She experienced Grade 2 acute and late toxicity that was successfully managed with medications. This experience shows that SMART is a feasible and effective treatment to control the abdominal oligometastatic disease for breast cancer. PMID:29805937

Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

PubMed

Kuang, Y H; Liu, Y J; Tang, L L; Wang, S M; Yan, G J; Liao, L Q

2018-05-25

Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

Comparison of Radiation Treatment Plans for Breast Cancer between 3D Conformal in Prone and Supine Positions in Contrast to VMAT and IMRT Supine Positions

NASA Astrophysics Data System (ADS)

Bejarano Buele, Ana Isabel

The treatment regimen for breast cancer patients typically involves Whole Breast Irradiation (WBI). The coverage and extent of the radiation treatment is dictated by location of tumor mass, breast tissue distribution, involvement of lymph nodes, and other factors. The current standard treatment approach used at our institution is a 3D tangential beam geometry, which involves two fields irradiating the breast, or a four field beam arrangement covering the whole breast and involved nodes, while decreasing the dose to organs as risk (OARs) such as the lung and heart. The coverage of these targets can be difficult to achieve in patients with unfavorable thoracic geometries, especially in those cases in which the planning target volume (PTV) is extended to the chest wall. It is a well-known fact that exposure of the heart to ionizing radiation has been proved to increase the subsequent rate of ischemic heart disease. In these cases, inverse planned treatments have become a proven alternative to the 3D approach. The goal of this research project is to evaluate the factors that affect our current techniques as well as to adapt the development of inverse modulated techniques for our clinic, in which breast cancer patients are one of the largest populations treated. For this purpose, a dosimetric comparison along with the evaluation of immobilization devices was necessary. Radiation treatment plans were designed and dosimetrically compared for 5 patients in both, supine and prone positions. For 8 patients, VMAT and IMRT plans were created and evaluated in the supine position. Skin flash incorporation for inverse modulated plans required measurement of the surface dose as well as an evaluation of breast volume changes during a treatment course. It was found that prone 3D conformal plans as well as the VMAT and IMRT plans are generally superior in sparing OARs to supine plans with comparable PTV coverage. Prone setup leads to larger shifts in breast volume as well as in positioning due to the difference in target geometry and nature of the immobilization device. IMRT and VMAT plans offer sparing of OARs from high dose regions with an increase of irradiated volume in the low dose regions. Skin flash incorporation was found to be accurate with the use of virtual bolus in the TPS for inverse modulated plans. Various factors influencing dose delivery in breast cancer radiation treatments were examined and quantified. Practical recommendations developed in the course of this project can improve our current techniques and provide alternatives to treat unique and challenging clinical cases.

Breast and colorectal cancer survivors' knowledge about their diagnosis and treatment.

PubMed

Nissen, Mary Jo; Tsai, Michaela L; Blaes, Anne H; Swenson, Karen K

2012-03-01

Aspects of a personal cancer history can have implications for future decisions regarding screening, diagnosis, and treatment. Clinicians must sometimes rely on patients' self-report of their medical history. This study assessed knowledge of details of cancer diagnosis and treatment among breast and colorectal cancer survivors. Written surveys were completed by 480 breast cancer survivors and 366 colorectal cancer survivors diagnosed between 1999 and 2008 at a large cancer center in the Minneapolis, MN, area (81% response rate). Responses were compared with cancer registry and medical records. Forty percent of breast cancer survivors and 65% of colorectal cancer survivors were unable to identify their stage of disease. Seven percent of breast cancer survivors and 21% of colorectal cancer survivors in whom regional nodes were examined did not know whether they had positive nodes. Accuracy of knowledge of estrogen and progesterone status among breast cancer survivors was 58% and 39%, respectively. Of breast cancer survivors treated with doxorubicin, 43% correctly identified it as a drug they had received. Their accuracy of identification of receipt of tamoxifen or specific aromatase inhibitors was >90%. Of colorectal cancer survivors treated with oxaliplatin, 52% correctly identified it as a drug they had received. Accuracy on many items decreased with patient age. This study identifies several gaps in adult cancer survivors' knowledge of details of their diagnosis and treatment that have implications for follow-up care. Provision of written treatment summaries to cancer survivors could help them obtain appropriate patient-centered long-term follow-up care.

Screening Breast MRI Outcomes in Routine Clinical Practice: Comparison to BI-RADS Benchmarks.

PubMed

Strigel, Roberta M; Rollenhagen, Jennifer; Burnside, Elizabeth S; Elezaby, Mai; Fowler, Amy M; Kelcz, Frederick; Salkowski, Lonie; DeMartini, Wendy B

2017-04-01

The BI-RADS Atlas 5th Edition includes screening breast magnetic resonance imaging (MRI) outcome benchmarks. However, the metrics are from expert practices and clinical trials of women with hereditary breast cancer predispositions, and it is unknown if they are appropriate for routine practice. We evaluated screening breast MRI audit outcomes in routine practice across a spectrum of elevated risk patients. This Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included all consecutive screening breast MRI examinations from July 1, 2010 to June 30, 2013. Examination indications were categorized as gene mutation carrier (GMC), personal history (PH) breast cancer, family history (FH) breast cancer, chest radiation, and atypia/lobular carcinoma in situ (LCIS). Outcomes were determined by pathology and/or ≥12 months clinical and/or imaging follow-up. We calculated abnormal interpretation rate (AIR), cancer detection rate (CDR), positive predictive value of recommendation for tissue diagnosis (PPV2) and biopsy performed (PPV3), and median size and percentage of node-negative invasive cancers. Eight hundred and sixty examinations were performed in 566 patients with a mean age of 47 years. Indications were 367 of 860 (42.7%) FH, 365 of 860 (42.4%) PH, 106 of 860 (12.3%) GMC, 14 of 860 (1.6%) chest radiation, and 8 of 22 (0.9%) atypia/LCIS. The AIR was 134 of 860 (15.6%). Nineteen cancers were identified (13 invasive, 4 DCIS, two lymph nodes), resulting in CDR of 19 of 860 (22.1 per 1000), PPV2 of 19 of 88 (21.6%), and PPV3 of 19 of 80 (23.8%). Of 13 invasive breast cancers, median size was 10 mm, and 8 of 13 were node negative (61.5%). Performance outcomes of screening breast MRI in routine clinical practice across a spectrum of elevated risk patients met the American College of Radiology Breast Imaging Reporting and Data System benchmarks, supporting broad application of these metrics. The indication of a personal history of treated breast cancer accounted for a large proportion (42%) of our screening examinations, with breast MRI performance in this population at least comparable to that of other screening indications. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Screening Breast MRI Outcomes in Routine Clinical Practice: Comparison to BI-RADS Benchmarks

PubMed Central

Strigel, Roberta M.; Rollenhagen, Jennifer; Burnside, Elizabeth S.; Elezaby, Mai; Fowler, Amy M.; Kelcz, Frederick; Salkowski, Lonie; DeMartini, Wendy B.

2017-01-01

Rationale and Objectives The BI-RADS Atlas 5th Edition includes screening breast magnetic resonance imaging (MRI) outcome benchmarks. However, the metrics are from expert practices and clinical trials of women with hereditary breast cancer predispositions, and it is unknown if they are appropriate for routine practice. We evaluated screening breast MRI audit outcomes in routine practice across a spectrum of elevated risk patients. Materials and Methods This Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included all consecutive screening breast MRI examinations from July 1, 2010 to June 30, 2013. Examination indications were categorized as gene mutation carrier (GMC), personal history (PH) breast cancer, family history (FH) breast cancer, chest radiation, and atypia/lobular carcinoma in situ (LCIS). Outcomes were determined by pathology and/or ≥12 months clinical and/or imaging follow-up. We calculated abnormal interpretation rate (AIR), cancer detection rate (CDR), positive predictive value of recommendation for tissue diagnosis (PPV2) and biopsy performed (PPV3), and median size and percentage of node-negative invasive cancers. Results Eight hundred and sixty examinations were performed in 566 patients with a mean age of 47 years. Indications were 367 of 860 (42.7%) FH, 365 of 860 (42.4%) PH, 106 of 860 (12.3%) GMC, 14 of 860 (1.6%) chest radiation, and 8 of 22 (0.9%) atypia/LCIS. The AIR was 134 of 860 (15.6%). Nineteen cancers were identified (13 invasive, 4 DCIS, two lymph nodes), resulting in CDR of 19 of 860 (22.1 per 1000), PPV2 of 19 of 88 (21.6%), and PPV3 of 19 of 80 (23.8%). Of 13 invasive breast cancers, median size was 10 mm, and 8 of 13 were node negative (61.5%). Conclusions Performance outcomes of screening breast MRI in routine clinical practice across a spectrum of elevated risk patients met the American College of Radiology Breast Imaging Reporting and Data System benchmarks, supporting broad application of these metrics. The indication of a personal history of treated breast cancer accounted for a large proportion (42%) of our screening examinations, with breast MRI performance in this population at least comparable to that of other screening indications. PMID:27986508

Comparison of FDG-PET with MIBI-SPECT in the detection of breast cancer and axillary lymph node metastasis.

PubMed

Yutani, K; Shiba, E; Kusuoka, H; Tatsumi, M; Uehara, T; Taguchi, T; Takai, S I; Nishimura, T

2000-01-01

The purpose of this work was to compare [18F]2-deoxy-2-fluoro-D-glucose (FDG) PET and 99mTc-methoxyisobutylisonitrile (MIBI) SPECT in the detection of breast cancer and axillary lymph node metastasis in the same patients. FDG-PET and MIBI-SPECT were performed within 3 days for 40 women (age range 25-86 years old) with suspected breast cancer, in whom biopsies and/or mastectomies were performed. Both images were visually assessed, and the count ratio between tumor and normal tissue (T/N ratio) was calculated. Thirty-eight patients had breast cancer, and the remaining two had benign breast lesions. The sensitivities of FDG-PET and MIBI-SPECT were 78.9 and 76.3% for breast cancer and 50.0 and 37.5% for axillary lymph node metastasis, respectively. The T/N ratio of breast cancer was significantly higher in FDG-PET (6.01 +/- 3.08 mean +/- SD) than that in MIBI-SPECT (3.48 +/- 1.21) (p = 0.01). Nonmalignant diffuse uptake of FDG in the breasts and the accumulation of MIBI in heart and liver occasionally obscured tumor uptake. These results indicate that MIBI-SPECT is comparable with FDG-PET in detecting breast cancer. Neither FDG-PET nor MIBI-SPECT is sufficiently sensitive to rule out axillary lymph node metastasis.

[Application of digital 3D technique combined with nanocarbon-aided navigation in endoscopic sentinel lymph node biopsy for breast cancer].

PubMed

Zhang, Pu-Sheng; Luo, Yun-Feng; Yu, Jin-Long; Fang, Chi-Hua; Shi, Fu-Jun; Deng, Jian-Wen

2016-08-20

To study the clinical value of digital 3D technique combined with nanocarbon-aided navigation in endoscopic sentinel lymph node biopsy for breast cancer. Thirty-nine female patients with stage I/II breast cancer admitted in our hospital between September 2014 and September 2015 were recruited. CT lymphography data of the patients were segmented to reconstruct digital 3D models, which were imported into FreeForm Modeling Surgical System Platform for visual simulation surgery before operation. Endoscopic sentinel lymph node biopsy and endoscopic axillary lymph node dissection were then carried out, and the accuracy and clinical value of digital 3D technique in endoscopic sentinel lymph node biopsy were analyzed. s The 3D models faithfully represented the surgical anatomy of the patients and clearly displayed the 3D relationship among the sentinel lymph nodes, axillary lymph nodes, axillary vein, pectoralis major, pectoralis minor muscle and latissimus dorsi. In the biopsy, the detection rate of sentinel lymph nodes was 100% in the patients with a coincidence rate of 87.18% (34/39), a sensitivity of 91.67% (11/12), and a false negative rate of 8.33% (1/12). Complications such as limb pain, swelling, wound infection, and subcutaneouseroma were not found in these patients 6 months after the operation. Endoscopic sentinel lymph node biopsy assisted by digital 3D technique and nanocarbon-aided navigation allows a high detection rate of sentinel lymph nodes with a high sensitivity and a low false negative rate and can serve as a new method for sentinel lymph node biopsy for breast cancer.

Negative Regulation of NF-κB by the ING4 Tumor Suppressor in Breast Cancer

PubMed Central

Byron, Sara A.; Min, Elizabeth; Thal, Tanya S.; Hostetter, Galen; Watanabe, Aprill T.; Azorsa, David O.; Little, Tanya H.; Tapia, Coya; Kim, Suwon

2012-01-01

Nuclear Factor kappa B (NF-κB) is a key mediator of normal immune response but contributes to aggressive cancer cell phenotypes when aberrantly activated. Here we present evidence that the Inhibitor of Growth 4 (ING4) tumor suppressor negatively regulates NF-κB in breast cancer. We surveyed primary breast tumor samples for ING4 protein expression using tissue microarrays and a newly generated antibody. We found that 34% of tumors expressed undetectable to low levels of the ING4 protein (n = 227). Tumors with low ING4 expression were frequently large in size, high grade, and lymph node positive, suggesting that down-regulation of ING4 may contribute to breast cancer progression. In the same tumor set, we found that low ING4 expression correlated with high levels of nuclear phosphorylated p65/RelA (p-p65), an activated form of NF-κB (p = 0.018). Fifty seven percent of ING4-low/p-p65-high tumors were lymph node-positive, indicating a high metastatic tendency of these tumors. Conversely, ectopic expression of ING4 inhibited p65/RelA phosphorylation in T47D and MCF7 breast cancer cells. In addition, ING4 suppressed PMA-induced cell invasion and NF-κB-target gene expression in T47D cells, indicating that ING4 inhibited NF-κB activity in breast cancer cells. Supportive of the ING4 function in the regulation of NF-κB-target gene expression, we found that ING4 expression levels inversely correlated with the expression of NF-κB-target genes in primary breast tumors by analyzing public gene expression datasets. Moreover, low ING4 expression or high expression of the gene signature composed of a subset of ING4-repressed NF-κB-target genes was associated with reduced disease-free survival in breast cancer patients. Taken together, we conclude that ING4 negatively regulates NF-κB in breast cancer. Consequently, down-regulation of ING4 leads to activation of NF-κB, contributing to tumor progression and reduced disease-free patient survival in breast cancer. PMID:23056468

Both high expression of pyruvate kinase M2 and vascular endothelial growth factor-C predicts poorer prognosis in human breast cancer.

PubMed

Lin, Yang; Liu, Fangfang; Fan, Yu; Qian, Xiaolong; Lang, Ronggang; Gu, Feng; Gu, Jun; Fu, Li

2015-01-01

Pyruvate kinase M2 (PKM2) and vascular endothelial growth factor-C (VEGF-C) have been known to play an important role in tumorigenesis and tumor progression in breast cancer. However, the association between PKM2 and VEGF-C in breast cancer remains unclear. In the present study, a total of 218 specimens from breast cancer patients and 26 paired breast tumors with adjacent normal tissues as well as two breast cancer cell lines were enrolled to investigate the correlation between PKM2 and VEGF-C. We found that PKM2 and VEGF-C mRNA levels were both significantly increasing in breast tumors compared with adjacent normal tissues. Knockdown of PKM2 mRNA expression resulted in VEGF-C mRNA and protein down-regulated as well as cell proliferation inhibited. A positive correlation between PKM2 and VEGF-C expression was identified by immunohistochemical analyses of 218 specimens of patients with breast cancer (P=0.023). PKM2 high expression was significantly correlated with histological grade (P=0.030), lymph node stage (P=0.001), besides VEGF-C high expression was significantly associated with lymphovascular invasion (P=0.012). While combined high expression of PKM2 and VEGF-C was found to be associated with worse histological grade, more lymph node metastasis, more lymphovascular invasion, shorter progression free survival (PFS), and poorer overall survival (OS) in human breast cancer. The results of the present study suggested that PKM2 expression was correlated with VEGF-C expression, and combination of PKM2 and VEGF-C levels had the better prognostic significance in predicting the poor outcome of patients with breast cancer.

Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer

PubMed Central

Han, Wonshik; Han, Mi-Ryung; Kang, Jason Jongho; Bae, Ji-Yeon; Lee, Ji Hyun; Bae, Young Ju; Lee, Jeong Eon; Shin, Hyuk-Jae; Hwang, Ki-Tae; Hwang, Sung-Eun; Kim, Sung-Won; Noh, Dong-Young

2006-01-01

Background A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer. Methods We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group). Results Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values <0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052). Conclusion Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples. PMID:16608533

Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

PubMed Central

Swain, Sandra M.; Tang, Gong; Geyer, Charles E.; Rastogi, Priya; Atkins, James N.; Donnellan, Paul P.; Fehrenbacher, Louis; Azar, Catherine A.; Robidoux, André; Polikoff, Jonathan A.; Brufsky, Adam M.; Biggs, David D.; Levine, Edward A.; Zapas, John L.; Provencher, Louise; Northfelt, Donald W.; Paik, Soonmyung; Costantino, Joseph P.; Mamounas, Eleftherios P.; Wolmark, Norman

2013-01-01

Purpose Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. Results There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Conclusion Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed. PMID:23940225

Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial.

PubMed

Swain, Sandra M; Tang, Gong; Geyer, Charles E; Rastogi, Priya; Atkins, James N; Donnellan, Paul P; Fehrenbacher, Louis; Azar, Catherine A; Robidoux, André; Polikoff, Jonathan A; Brufsky, Adam M; Biggs, David D; Levine, Edward A; Zapas, John L; Provencher, Louise; Northfelt, Donald W; Paik, Soonmyung; Costantino, Joseph P; Mamounas, Eleftherios P; Wolmark, Norman

2013-09-10

Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial.

PubMed

Giuliano, Armando E; Ballman, Karla V; McCall, Linda; Beitsch, Peter D; Brennan, Meghan B; Kelemen, Pond R; Ollila, David W; Hansen, Nora M; Whitworth, Pat W; Blumencranz, Peter W; Leitch, A Marilyn; Saha, Sukamal; Hunt, Kelly K; Morrow, Monica

2017-09-12

The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology). To determine whether the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection. The ACOSOG Z0011 phase 3 randomized clinical trial enrolled patients from May 1999 to December 2004 at 115 sites (both academic and community medical centers). The last date of follow-up was September 29, 2015, in the ACOSOG Z0011 (Alliance) trial. Eligible patients were women with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases. All patients had planned lumpectomy, planned tangential whole-breast irradiation, and adjuvant systemic therapy. Third-field radiation was prohibited. The primary outcome was overall survival with a noninferiority hazard ratio (HR) margin of 1.3. The secondary outcome was disease-free survival. Among 891 women who were randomized (median age, 55 years), 856 (96%) completed the trial (446 in the SLND alone group and 445 in the ALND group). At a median follow-up of 9.3 years (interquartile range, 6.93-10.34 years), the 10-year overall survival was 86.3% in the SLND alone group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; noninferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95% CI, 0.62-1.17]; P = .32). Between year 5 and year 10, 1 regional recurrence was seen in the SLND alone group vs none in the ALND group. Ten-year regional recurrence did not differ significantly between the 2 groups. Among women with T1 or T2 invasive primary breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases, 10-year overall survival for patients treated with sentinel lymph node dissection alone was noninferior to overall survival for those treated with axillary lymph node dissection. These findings do not support routine use of axillary lymph node dissection in this patient population based on 10-year outcomes. clinicaltrials.gov Identifier: NCT00003855.

The Impact of Axillary Lymph Node Surgery on Breast Skin Thickening During and After Radiation Therapy for Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torres, Mylin A., E-mail: matorre@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; Yang, Xiaofeng

Purpose: This prospective study was conducted to determine predictors of epidermal thickening during and after whole-breast radiation therapy (XRT) using objective measurements acquired with ultrasound. Methods and Materials: After breast-conserving surgery, 70 women received a definitive course of whole-breast XRT (50 Gy plus boost). Prior to XRT, at week 6 of XRT, and 6 weeks after XRT, patients underwent objective ultrasound measurements of epidermal thickness over the lumpectomy cavity and all 4 quadrants of the treated breast. A skin thickness ratio (STRA) was then generated normalizing for corresponding measurements taken of the untreated breast. Results: Baseline measurements indicated that 87% of patientsmore » had skin thickening in the treated versus untreated breast (mean increase, 27%; SD, 0.29) prior to XRT. The STRA increased significantly by week 6 of XRT (mean, 25%; SD, 0.46) and continued to increase significantly 6 weeks after XRT (mean, 33%; SD, 0.46) above baseline measurements (P<.001 for both time points). On multivariate analysis, breast volume (P=.003) and surgical evaluation of the axilla with full lymph node dissection (P<.05) predicted for more severe changes in the STRA 6 weeks after XRT compared with baseline. STRA measurements correlated with physician ratings of skin toxicity according to Radiation Therapy Oncology Group grading criteria. Conclusions: This is one of the first studies to objectively document that lymph node surgery affects XRT-induced skin thickening in patients with breast cancer. Surgical evaluation of the axilla with complete lymph node dissection was associated with the most severe XRT-induced skin changes after XRT completion. These results may inform future studies aimed at minimizing side effects of XRT and surgery, particularly when surgical lymph node assessments may not alter breast cancer management or outcome.« less

Cost effectiveness of tac versus fac in adjuvant treatment of node-positive breast cancer

PubMed Central

Mittmann, N.; Verma, S.; Koo, M.; Alloul, K.; Trudeau, M.

2010-01-01

Background This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi–Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (tac) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (fac) following primary surgery for breast cancer in women with operable, axillary lymph node–positive breast cancer. Methods A Markov model looking at two time phases—5-year treatment and long-term follow-up—was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were “no recurrence,” “locoregional recurrence,” “distant recurrence,” and “death.” Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration costs, relapse and follow-up costs, costs for management of adverse events, and costs for granulocyte colony-stimulating factor (g-csf) prophylaxis. A 5% discount rate was applied to costs and outcomes alike. Health utilities were obtained from published sources. Results For tac as compared with fac, the incremental cost was $6921 per life-year (ly) gained and $6,848 per quality-adjusted life-year (qaly) gained. The model was robust to changes in input variables (for example, febrile neutropenia rate, utility). When g-csf and antibiotics were given prophylactically before every cycle, the incremental ratios increased to $13,183 and $13,044 respectively. Conclusions Compared with fac, tac offered improved response at a higher cost. The cost-effectiveness ratios were low, indicating good economic value in the adjuvant setting of node-positive breast cancer patients. PMID:20179798

Case-only analyses of the associations between polymorphisms in the metastasis modifying genes BRMS1 and SIPA1 and breast tumor characteristics, lymph node metastasis, and survival

PubMed Central

Roberts, Michelle R.; Hong, Chi-Chen; Edge, Stephen B.; Yao, Song; Bshara, Wiam; Higgins, Michael J.; Freudenheim, Jo L.; Ambrosone, Christine B.

2013-01-01

Introduction Lymph node metastases and tumor characteristics predict breast cancer prognosis but correlate imperfectly with likelihood of metastatic relapse. Discovery of genetic polymorphisms affecting metastasis may improve identification of patients requiring aggressive adjuvant therapy to prevent recurrence. We investigated associations between several variants in the BRMS1 and SIPA1 metastasis-modifying genes and lymph node metastases, tumor subtype and grade, recurrence, disease-free survival and overall survival. Methods This cross-sectional and prospective prognostic analysis included 859 patients who received surgery for incident breast cancer at Roswell Park Cancer Institute, participated in the DataBank and BioRepository shared resource, and had DNA, clinical, and pathology data available for analysis. Genotyping for BRMS1 (rs11537993, rs3116068, and rs1052566) and SIPA1 (rs75894763, rs746429, rs3741378, and rs2306364) polymorphisms was performed using Sequenom® iPLEX Gold and Taqman® real-time PCR assays. Logistic and Cox proportional hazards regressions were used to estimate odds ratios (OR) and hazard ratios (HR), respectively. Results BRMS1 rs1052566 heterozygous individuals were more likely to have node positive tumors (OR=1.58, 95% CI 1.13-2.23), although there was no dose-response relationship, and those with at least one variant allele were less likely to have the luminal B subtype (AG+AA: OR=0.59, 95% CI 0.36-0.98). BRMS1 rs3116068 was associated with increased likelihood of having the luminal B and the HER2-enriched tumor subtype (Ptrend=0.03). Two SIPA1 SNPs, rs746429 and rs2306364, were associated with decreased risk of triple negative tumors (Ptrend=0.04 and 0.07, respectively). Presence of 8 or more risk alleles was associated with an increased likelihood of having a node positive tumor (OR=2.14, 95% CI 1.18-3.36, Ptrend = 0.002). There were no significant associations with survival. Conclusions Polymorphisms in metastasis-associated genes may be related to tumor characteristics and lymph node metastasis, but not survival. Future evaluation of metastasis modifying gene variants is necessary to better understand the biology of metastasis. PMID:23771732

Case-only analyses of the associations between polymorphisms in the metastasis-modifying genes BRMS1 and SIPA1 and breast tumor characteristics, lymph node metastasis, and survival.

PubMed

Roberts, Michelle R; Hong, Chi-Chen; Edge, Stephen B; Yao, Song; Bshara, Wiam; Higgins, Michael J; Freudenheim, Jo L; Ambrosone, Christine B

2013-06-01

Lymph node metastases and tumor characteristics predict breast cancer prognosis but correlate imperfectly with likelihood of metastatic relapse. Discovery of genetic polymorphisms affecting metastasis may improve identification of patients requiring aggressive adjuvant therapy to prevent recurrence. We investigated associations between several variants in the BRMS1 and SIPA1 metastasis-modifying genes and lymph node metastases, tumor subtype and grade, recurrence, disease-free survival, and overall survival. This cross-sectional and prospective prognostic analysis included 859 patients who received surgery for incident breast cancer at Roswell Park Cancer Institute, participated in the DataBank and BioRepository shared resource, and had DNA, clinical, and pathology data available for analysis. Genotyping for BRMS1 (rs11537993, rs3116068, and rs1052566) and SIPA1 (rs75894763, rs746429, rs3741378, and rs2306364) polymorphisms was performed using Sequenom(®) iPLEX Gold and Taqman(®) real-time PCR assays. Logistic and Cox proportional hazards regressions were used to estimate odds ratios (OR) and hazard ratios (HR), respectively. BRMS1 rs1052566 heterozygous individuals were more likely to have node-positive tumors (OR = 1.58, 95 % CI 1.13-2.23), although there was no dose-response relationship, and those with at least one variant allele were less likely to have the luminal B subtype (AG + AA: OR = 0.59, 95 % CI 0.36-0.98). BRMS1 rs3116068 was associated with increased likelihood of having the luminal B and the HER2-enriched tumor subtype (P trend = 0.03). Two SIPA1 SNPs, rs746429 and rs2306364, were associated with decreased risk of triple-negative tumors (P trend = 0.04 and 0.07, respectively). Presence of 8 or more risk alleles was associated with an increased likelihood of having a node-positive tumor (OR = 2.14, 95 % CI 1.18-3.36, P trend = 0.002). There were no significant associations with survival. Polymorphisms in metastasis-associated genes may be related to tumor characteristics and lymph node metastasis, but not survival. Future evaluation of metastasis-modifying gene variants is necessary to better understand the biology of metastasis.

Partial lower axillary dissection for patients with clinically node-negative breast cancer.

PubMed

Kodama, H; Mise, K; Kan, N

2012-01-01

To evaluate retrospectively the outcomes of partial lower axillary lymph node dissection caudal to the intercostobrachial nerve in patients with clinically node-negative (N(0)) breast cancer. Numbers of dissected and metastatic nodes, overall and disease-free survival rates, postoperative complication rates, and axillary recurrence were compared between patients who underwent breast cancer surgery with partial axillary node dissection (n = 1043) and historical controls who underwent conventional dissection (n = 1084). The 5-year overall and disease-free survival rates were 95.6% and 89.7%, and 94.9% and 88.4%, respectively, in the partial dissection and conventional dissection groups; the differences were not significant. Mean duration of surgery (41.6 min versus 60.9 min), intraoperative blood loss (28.0 ml versus 51.3 ml), volume of lymphatic drainage at 2 weeks postoperatively (488 ml versus 836 ml), and persistent arm lymphoedema (0.0% versus 11.8%) were significantly different between the partial and conventional dissection groups, respectively. Partial axillary lymph node dissection was associated with similar survival rates (but lower postoperative complication rates) compared with conventional axillary dissection and is recommended in patients with N(0) breast cancer.

Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study.

PubMed

Martín, Miguel; Ruiz, Amparo; Ruiz Borrego, Manuel; Barnadas, Agustí; González, Sonia; Calvo, Lourdes; Margelí Vila, Mireia; Antón, Antonio; Rodríguez-Lescure, Alvaro; Seguí-Palmer, Miguel Angel; Muñoz-Mateu, Montserrat; Dorca Ribugent, Joan; López-Vega, José Manuel; Jara, Carlos; Espinosa, Enrique; Mendiola Fernández, César; Andrés, Raquel; Ribelles, Nuria; Plazaola, Arrate; Sánchez-Rovira, Pedro; Salvador Bofill, Javier; Crespo, Carmen; Carabantes, Francisco J; Servitja, Sonia; Chacón, José Ignacio; Rodríguez, César A; Hernando, Blanca; Álvarez, Isabel; Carrasco, Eva; Lluch, Ana

2013-07-10

Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established. Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival. After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%). For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.

Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome.

PubMed

Joshi, M G; Lee, A K; Loda, M; Camus, M G; Pedersen, C; Heatley, G J; Hughes, K S

1996-02-01

Although breast cancer in men is far less common than breast cancer in women, it is associated with a less favorable prognosis. Conventional histopathologic features and new prognostic markers were evaluated to explain the less favorable survival outcome. Forty-six consecutive male breast carcinomas were studied for size, histologic and nuclear grade, histologic subtype, presence of carcinoma in situ, nipple involvement, lymphovascular invasion, hormone receptor status, c-erbB-2 protein overexpression, and p53 protein accumulation. These findings were correlated with survival. Of the 46 carcinomas, 4 were noninvasive and 42 were invasive. In the invasive carcinomas, the median patient age was 64 years, and the median tumor size was 2 cm. The predominant histologic patterns were invasive ductal (45%) and mixed invasive ductal and cribriform (28%). Most tumors were of low histologic and nuclear grades (histologic grades: I, 17%; II, 50%; III, 33%; nuclear grade: I, 12%; II, 44%; III, 44%). Of those surgically staged, 22 patients (60%) were lymph node positive and 15 patients (40%) were node negative. Stage at presentation was higher than in women (0, 10%; 1, 17%; 2, 50%; 3, 13%; 4, 10%). The estrogen and progesterone receptor status was positive in 76% and 83% of tumors, respectively. Lymphatic vessel invasion (63%) and nipple involvement (48%) were also more common than in women. True Paget's disease of the nipple was not seen; all cases with nipple ulceration were the result of direct tumor extension to the epidermis. Of the 17 tumors tested, 41% were c-erbB-2 positive and 29% were p53 positive. Survival analysis was limited by the relatively small cohort size. Five- and 10-year adjusted overall survival rates for invasive tumors were 76 +/- 7% and 42 +/- 9%, respectively. Skin and nipple involvement (P = 0.03) and c-erbB-2-positivity (P = 0.03) were significant predictors of adverse survival. Male breast carcinoma presents in an advanced stage with less favorable survival, despite low histologic grade, high estrogen receptor content, and small size. Anatomic factors may have been responsible for the poor survival outcome (i.e., paucity of breast tissue and close tumor proximity to skin and nipple, facilitating dermal lymphatic spread and early regional and distant metastasis).

A critical review of variables affecting the accuracy and false-negative rate of sentinel node biopsy procedures in early breast cancer.

PubMed

Vijayakumar, Vani; Boerner, Philip S; Jani, Ashesh B; Vijayakumar, Srinivasan

2005-05-01

Radionuclide sentinel lymph node localization and biopsy is a staging procedure that is being increasingly used to evaluate patients with invasive breast cancer who have clinically normal axillary nodes. The most important prognostic indicator in patients with invasive breast cancer is the axillary node status, which must also be known for correct staging, and influences the selection of adjuvant therapies. The accuracy of sentinel lymph node localization depends on a number of factors, including the injection method, the operating surgeon's experience and the hospital setting. The efficacy of sentinel lymph node mapping can be determined by two measures: the sentinel lymph node identification rate and the false-negative rate. Of these, the false-negative rate is the most important, based on a review of 92 studies. As sentinel lymph node procedures vary widely, nuclear medicine physicians and radiologists must be acquainted with the advantages and disadvantages of the various techniques. In this review, the factors that influence the success of different techniques are examined, and studies which have investigated false-negative rates and/or sentinel lymph node identification rates are summarized.

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

PubMed

García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

2016-01-01

Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Feasibility of anomaly detection and characterization using trans-admittance mammography with 60 × 60 electrode array

NASA Astrophysics Data System (ADS)

Zhao, Mingkang; Wi, Hun; Lee, Eun Jung; Woo, Eung Je; In Oh, Tong

2014-10-01

Electrical impedance imaging has the potential to detect an early stage of breast cancer due to higher admittivity values compared with those of normal breast tissues. The tumor size and extent of axillary lymph node involvement are important parameters to evaluate the breast cancer survival rate. Additionally, the anomaly characterization is required to distinguish a malignant tumor from a benign tumor. In order to overcome the limitation of breast cancer detection using impedance measurement probes, we developed the high density trans-admittance mammography (TAM) system with 60 × 60 electrode array and produced trans-admittance maps obtained at several frequency pairs. We applied the anomaly detection algorithm to the high density TAM system for estimating the volume and position of breast tumor. We tested four different sizes of anomaly with three different conductivity contrasts at four different depths. From multifrequency trans-admittance maps, we can readily observe the transversal position and estimate its volume and depth. Specially, the depth estimated values were obtained accurately, which were independent to the size and conductivity contrast when applying the new formula using Laplacian of trans-admittance map. The volume estimation was dependent on the conductivity contrast between anomaly and background in the breast phantom. We characterized two testing anomalies using frequency difference trans-admittance data to eliminate the dependency of anomaly position and size. We confirmed the anomaly detection and characterization algorithm with the high density TAM system on bovine breast tissue. Both results showed the feasibility of detecting the size and position of anomaly and tissue characterization for screening the breast cancer.

Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer.

PubMed

Grönberg, Malin; Ahlin, Cecilia; Naeser, Ylva; Janson, Eva Tiensuu; Holmberg, Lars; Fjällskog, Marie-Louise

2017-01-01

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

[Establishment of lymph node metastasis of MDA-MB-231 breast cancer model in nude mice].

PubMed

Wang, Le; Mi, Chengrong; Wang, Wen

2015-06-16

To establish lymph node metastasis of breast cancer model in nude mices using MDA-MB-231 cell lines or tumor masses. Divided twelve female nude mices of five weeks into A, B groups randomly. A group had seven nude mices, B group had five nude mices. A group nude mices were injected with MDA-MB-231 cells suspension into the second right mammary fat pad. Two weeks after emerged tumors, the orthotopic tumors of two nude mices of A group were dissected and then implanted into the second right mammary fat pad of B group nude mices. The other mices of A group continued to be fed. After six weeks of inoculation, we excised the tumors and the swollen lymph nodes in right axilla of all nude mices to make pathological examination. ① A group have a 7/7 tumor formation rate 7 days after implanted, B group was 5/5 5 days after implanted. ② The tumor volumes between the two groups had evident difference (P = 0.023), and the tumor volume of B group was bigger than A group. ③ A group had three nude mices which had one tumid lymph node respectively, the lymph node enlargement rate was 3/5; B group only had one nude mice that had one tumid lymph node, the lymph node enlargement rate was 1/5, the lymph node enlargement rate between the two groups showed no significant difference (P = 0.524). ④ The result of pathology in the two groups testified the tumors were invasive ductal carcinoma. The swollen lymph nodes in A group were reactive hyperplasia lymph nodes; the swollen lymph nodes in B group was metastatic lymph node. The method of orthotopic implantation with MDA-MB-231 tumor mass to establish lymph node metastasis of breast cancer model in nude mice, can provide a useful mean to research the lymph node metastasis mechanism of breast cancer.

Malignant neoplasm in the axilla of a male: suspected primary carcinoma of an accessory mammary gland.

PubMed

Takeyama, Hiroshi; Takahashi, Hiroyuki; Tabei, Isao; Fukuchi, Osamu; Nogi, Hiroko; Kinoshita, Satoki; Uchida, Ken; Morikawa, Toshiaki

2010-04-01

A 58-year-old Japanese male patient visited our hospital for evaluation of an elastic hard mass, measuring 80 x 50 mm, in the right axillary area. Incisional biopsy for suspected malignancy was performed, and histopathologic examination by hematoxylin-eosin (H&E) staining yielded a diagnosis of poorly differentiated adenocarcinoma metastatic from an unknown primary. As the tumor was immunohistochemically positive for both ER and PgR, metastatic breast cancer was strongly suspected. Ultrasonography, CT, and MRI revealed no evidence of tumors in the bilateral mammary glands. Detailed examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. After chemotherapy, the patient underwent tumor resection with axillary lymph node dissection. On the basis of the histological features of H&E-stained specimens and immunohistochemistry of the resected tumor, this case was diagnosed as breast cancer of unknown origin in a male. The tumor could have been an axillary lymph node metastasis from an occult breast carcinoma, or primary cancer arising in an accessory mammary gland.

Can Breast Cancer Biopsy Influence Sentinel Lymph Node Status?

PubMed

Giuliani, Michela; Patrolecco, Federica; Rella, Rossella; Di Giovanni, Silvia Eleonora; Infante, Amato; Rinaldi, Pierluigi; Romani, Maurizio; Mulè, Antonino; Arciuolo, Damiano; Belli, Paolo; Bonomo, Lorenzo

2016-12-01

We evaluated whether the needle size could influence metastasis occurrence in the axillary sentinel lymph node (SLN) in ultrasound-guided core needle biopsy (US-CNB) of breast cancer (BC). The data from all patients with breast lesions who had undergone US-CNB at our institution from January 2011 to January 2015 were retrospectively reviewed. A total of 377 BC cases were included using the following criteria: (1) percutaneous biopsy-proven invasive BC; and (2) SLN dissection with histopathologic examination. The patients were divided into 2 groups according to the needle size used: 14 gauge versus 16 or 18 gauge. SLN metastasis classification followed the 7th American Joint Committee on Cancer (2010) TNM pathologic staging factors: macrometastases, micrometastases, isolated tumor cells, or negative. Only macrometastases and micrometastases were considered positive, and the positive and negative rates were calculated for the overall population and for both needle size groups. Of the 377 BC cases, 268 US-CNB procedures were performed using a 14-gauge needle and 109 with a 16- or 18-gauge needle, respectively. The negative rate was significantly related statistically with the needle size, with a greater prevalence in the 14-gauge group on both extemporaneous analysis (P = .019) and definitive analysis (P = .002). The macrometastasis rate was 17% (63 of 377) for the 14-gauge and 3% (12 of 377) for the 16- and 18-gauge needles, respectively. Our preliminary results have suggested that use of a large needle size in CNB does not influence SLN status; thus, preoperative breast biopsy can be considered a safe procedure in the diagnosis of malignant breast lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Sentinel Lymph Node Detection Using Carbon Nanoparticles in Patients with Early Breast Cancer

PubMed Central

Lu, Jianping; Zeng, Yi; Chen, Xia; Yan, Jun

2015-01-01

Purpose Carbon nanoparticles have a strong affinity for the lymphatic system. The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy using carbon nanoparticles in early breast cancer and to optimize the application procedure. Methods Firstly, we performed a pilot study to demonstrate the optimized condition using carbon nanoparticles for sentinel lymph nodes (SLNs) detection by investigating 36 clinically node negative breast cancer patients. In subsequent prospective study, 83 patients with clinically node negative breast cancer were included to evaluate SLNs using carbon nanoparticles. Another 83 SLNs were detected by using blue dye. SLNs detection parameters were compared between the methods. All patients irrespective of the SLNs status underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. Results In pilot study, a 1 ml carbon nanoparticles suspension used 10–15min before surgery was associated with the best detection rate. In subsequent prospective study, with carbon nanoparticles, the identification rate, accuracy, false negative rate was 100%, 96.4%, 11.1%, respectively. The identification rate and accuracy were 88% and 95.5% with 15.8% of false negative rate using blue dye technique. The use of carbon nanoparticles suspension showed significantly superior results in identification rate (p = 0.001) and reduced false-negative results compared with blue dye technique. Conclusion Our study demonstrated feasibility and accuracy of using carbon nanoparticles for SLNs mapping in breast cancer patients. Carbon nanoparticles are useful in SLNs detection in institutions without access to radioisotope. PMID:26296136

Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients.

PubMed

Urru, Silvana Anna Maria; Gallus, Silvano; Bosetti, Cristina; Moi, Tiziana; Medda, Ricardo; Sollai, Elisabetta; Murgia, Alma; Sanges, Francesca; Pira, Giovanna; Manca, Alessandra; Palmas, Dolores; Floris, Matteo; Asunis, Anna Maria; Atzori, Francesco; Carru, Ciriaco; D'Incalci, Maurizio; Ghiani, Massimo; Marras, Vincenzo; Onnis, Daniela; Santona, Maria Cristina; Sarobba, Giuseppina; Valle, Enrichetta; Canu, Luisa; Cossu, Sergio; Bulfone, Alessandro; Rocca, Paolo Cossu; De Miglio, Maria Rosaria; Orrù, Sandra

2018-01-08

To provide further information on the clinical and pathological prognostic factors in triple-negative breast cancer (TNBC), for which limited and inconsistent data are available. Pathological characteristics and clinical records of 841 TNBCs diagnosed between 1994 and 2015 in four major oncologic centers from Sardinia, Italy, were reviewed. Multivariate hazard ratios (HRs) for mortality and recurrence according to various clinicopathological factors were estimated using Cox proportional hazards models. After a mean follow-up of 4.3 years, 275 (33.3%) TNBC patients had a progression of the disease and 170 (20.2%) died. After allowance for study center, age at diagnosis, and various clinicopathological factors, all components of the TNM staging system were identified as significant independent prognostic factors for TNBC mortality. The HRs were 3.13, 9.65, and 29.0, for stage II, III and IV, respectively, vs stage I. Necrosis and Ki-67 > 16% were also associated with increased mortality (HR: 1.61 and 1.99, respectively). Patients with tumor histotypes other than ductal invasive/lobular carcinomas had a more favorable prognosis (HR: 0.40 vs ductal invasive carcinoma). No significant associations with mortality were found for histologic grade, tumor infiltrating lymphocytes, and lymphovascular invasion. Among lymph node positive TNBCs, lymph node ratio appeared to be a stronger predictor of mortality than pathological lymph nodes stage (HR: 0.80 for pN3 vs pN1, and 3.05 for >0.65 vs <0.21 lymph node ratio), respectively. Consistent results were observed for cancer recurrence, except for Ki-67 and necrosis that were not found to be significant predictors for recurrence. This uniquely large study of TNBC patients provides further evidence that, besides tumor stage at diagnosis, lymph node ratio among lymph node positive tumors is an additional relevant predictor of survival and tumor recurrence, while Ki-67 seems to be predictive of mortality, but not of recurrence.

Aberrant expression of decoy receptor 3 in human breast cancer: relevance to lymphangiogenesis.

PubMed

Wu, Qiuwan; Zheng, Yahong; Chen, Donghan; Li, Xiaohong; Lu, Chuanhui; Zhang, Zhiming

2014-05-15

Decoy receptor 3 (DcR3), a decoy receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily, is overexpressed in some forms of cancer. It was recently reported that DcR3 could protect endothelial cells from apoptosis, implying a potential role in the development of vessels, whereas its role in the lymphangiogenesis remains unclear. In the present study, we studied the DcR3 expression and its relationship with the lymphatic microvessel density (LMVD) to investigate if it played a role in the lymph metastasis of human breast cancer. Real-time polymerase chain reaction and immunohistochemistry were performed to measure the messenger RNA and protein expression of DcR3 in the breast cancer tissues, noncancerous counterparts, and axillary lymph node from 63 patients. LMVD in these specimens was assessed by counting the D2-40 labeled-microvessels. Furthermore, the correlations between DcR3 expression and LMVD and other clinicopathologic parameters were analyzed. DcR3 was overexpressed in the breast cancer tissue of 58 patients (92.1%) and was also expressed in vascular endothelial cells and tumor cells in the lymph nodes. LMVD in cancer tissue and lymph nodes were both positively correlated to the aberrant expression of DcR3. The relevance between DcR3 overexpression and LMVD revealed the existence of possible links between DcR3 and lymphangiogenesis. Based on these findings, it is important to further explore the regulation of lymphangiogenesis operated by the reverse tumor necrosis factor signaling of DcR3. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study

PubMed Central

Pivot, Xavier B.; Jacot, William; Naman, Hervé L.; Spaeth, Dominique; Misset, Jean-Louis; Largillier, Rémy; Sautiere, Jean-Loup; de Roquancourt, Anne; Pomel, Christophe; Rouanet, Philippe; Rouzier, Roman; Penault-Llorca, Frederique M.

2015-01-01

Background. The 21-gene Oncotype DX Recurrence Score assay is a validated assay to help decide the appropriate treatment for estrogen receptor-positive (ER+), early-stage breast cancer (EBC) in the adjuvant setting. The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines. This prospective multicenter study is the first to assess the impact of the Oncotype DX assay in the French clinical setting. Methods. A total of 100 patients with ER+, human epidermal growth factor receptor 2-negative EBC, and node-negative (pN0) disease or micrometastases in up to 3 lymph nodes (pN1mi) were enrolled. Treatment recommendations, physicians’ confidence before and after knowing the Recurrence Score value, and physicians’ perception of the assay were recorded. Results. Of the 100 patients, 95 were evaluable (83 pN0, 12 pN1mi). Treatment recommendations changed in 37% of patients, predominantly from chemoendocrine to endocrine treatment alone. The proportion of patients recommended chemotherapy decreased from 52% pretest to 25% post-test. Of patients originally recommended chemotherapy, 61% were recommended endocrine treatment alone after receiving the Recurrence Score result. For both pN0 and pN1mi patients, post-test recommendations appeared to follow the Recurrence Score result for low and high values. Physicians’ confidence improved significantly. Conclusion. These are the first prospective data on the impact of the Oncotype DX assay on adjuvant treatment decisions in France. Using the assay was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. These data are consistent with those presented from European and non-European studies. Implications for Practice: This study shows that in estrogen receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer (either node-negative or with micrometastases in up to 3 lymph nodes), Oncotype DX testing is associated with a treatment recommendation change in more than a third of patients (primarily from chemoendocrine treatment to endocrine treatment alone but also in the opposite direction) and an overall reduction in chemotherapy use. These results are consistent with those from other decision impact studies worldwide and further emphasize the role of Oncotype DX testing in management of early breast cancer, as reflected in international treatment guidelines. PMID:26112003

Arm morbidity of axillary dissection with sentinel node biopsy versus delayed axillary dissection.

PubMed

Ballal, Helen; Hunt, Catherine; Bharat, Chrianna; Murray, Kevin; Kamyab, Roshi; Saunders, Christobel

2018-02-02

Staging of axillary lymph nodes in breast cancer is important for prognostication and planning of adjuvant therapy. The traditional practice of proceeding to axillary lymph node dissection (ALND) if sentinel lymph node biopsy (SLNB) is positive is being challenged and clinical trials are underway. For many centres, this will mean a move away from intra-operative SLNB assessment and utilization of a second procedure to perform ALND. It is sometimes perceived that a delayed ALND results in increased tissue damage and thus increased morbidity. We compared morbidity in those undergoing SLNB only, or ALND as a one- or two-stage procedure. A retrospective review of a prospectively collected institutional database was used to review rates of lymphoedema and shoulder function in women undergoing breast cancer surgery between 2008 and 2012. The overall lymphoedema rate in 745 patients was 8.2% at 12 months. There was no difference in lymphoedema rates between those undergoing immediate or delayed ALND (17.8 and 8.6%, respectively, P = 0.092). Post-operative shoulder elevation, odds ratio (OR) = 0.390, 95% confidence interval (CI) = (0.218, 0.698) and abduction, OR = 0.437 (95% CI = (0.271, 0.705)) were reduced if an ALND was performed although there was no difference between immediate or delayed. ALND remains a risk factor for post-operative morbidity. There is no increased risk of lymphoedema or shoulder function deficit with a positive SLNB and delayed ALND compared to immediate ALND. © 2018 Royal Australasian College of Surgeons.

Is axillary surgery beneficial for patients with adenoid cystic carcinoma of the breast?

PubMed

Welsh, Jessemae L; Keeney, Michael G; Hoskin, Tanya L; Glazebrook, Katrina N; Boughey, Judy C; Shah, Sejal S; Hieken, Tina J

2017-11-01

Adenoid cystic carcinoma (ACC) is a rare, typically triple-negative, breast cancer reported to have a favorable prognosis and low rate of nodal metastasis. No consensus guidelines exist for axillary staging and treatment. We identified all patients with ACC evaluated at our institution from January 1994 to August 2016. Patient, tumor, and treatment variables were abstracted and analyzed. We identified 20 pure ACCs (0.13% of all invasive breast cancers) with size range 0.2-4.8 cm, in 19 women, median age 59 years. Preoperative axillary ultrasound was normal in 10/13 women and suspicious in 3/13 who had a subsequent negative lymph node fine needle aspiration (FNA). Fifteen patients (75%) had sentinel lymph node surgery and were pathologically node-negative, while the remaining five had no axillary surgery. With 3.6 years median follow-up (range 0.2-38.6 years), three patients experienced an in-breast recurrence at 2, 16, and 17 years, respectively, while none recurred in regional nodes. We observed no cases of nodal metastasis in 20 consecutive cases of ACC of the breast. Preoperative axillary ultrasound with FNA of suspicious nodes accurately predicted pathologic nodal stage. These data suggest axillary surgery might be omitted safely in patients with pure ACC and a clinically negative axilla. © 2017 Wiley Periodicals, Inc.

History, present status and future of sentinel node biopsy in breast cancer. The Mary Béves Lecture.

PubMed

Mansel, R E; Khonji, N I; Clarke, D

2000-01-01

The word Sentinel' is defined in The Oxford English Dictionary as 'a guard, one who keeps watch or a sentry'. When translated to the concept of a tumour and its lymph node drainage, the sentinel node could be interpreted to mean the lymph node that guards or keeps watch over a tumour. The sentinel lymph node can thus be defined as the first lymph node that drains a primary tumour within the regional lymphatic basin of that tumour. We know that tumour progression in breast cancer often occurs in an orderly, progressive fashion. So in theory, if the sentinel node is tumour free then the rest of the nodes in the lymphatic basin should also be uninvolved by the tumour.

Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization.

PubMed

Pauletti, G; Godolphin, W; Press, M F; Slamon, D J

1996-07-04

Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.

Breast Cancer Metastasis to the Stomach That Was Diagnosed after Endoscopic Submucosal Dissection.

PubMed

Kita, Masahide; Furukawa, Masashi; Iwamuro, Masaya; Hori, Keisuke; Kawahara, Yoshiro; Taira, Naruto; Nogami, Tomohiro; Shien, Tadahiko; Tanaka, Takehiro; Doihara, Hiroyoshi; Okada, Hiroyuki

2016-01-01

A 52-year-old woman presented with stage IIB primary breast cancer (cT2N1M0), which was treated using neoadjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel). However, the tumor persisted in patchy areas; therefore, we performed modified radical mastectomy and axillary lymph node dissection. Routine endoscopy at 8 months revealed a depressed lesion on the gastric angle's greater curvature, and histology revealed signet ring cell proliferation. We performed endoscopic submucosal dissection for gastric cancer, although immunohistochemistry revealed that the tumor was positive for estrogen receptor, mammaglobin, and gross cystic disease fluid protein-15 (E-cadherin-negative). Therefore, we revised the diagnosis to gastric metastasis from the breast cancer.

Surgeon specialization and use of sentinel lymph node biopsy for breast cancer.

PubMed

Yen, Tina W F; Laud, Purushuttom W; Sparapani, Rodney A; Nattinger, Ann B

2014-02-01

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in patients with clinically node-negative breast cancer. It is not known whether SLNB rates differ by surgeon expertise. If surgeons with less breast cancer expertise are less likely to offer SLNB to these patients, this practice pattern could lead to unnecessary axillary lymph node dissections and lymphedema. To explore potential measures of surgical expertise (including a novel objective specialization measure: percentage of a surgeon's operations performed for breast cancer determined from Medicare claims) on the use of SLNB for invasive breast cancer. A population-based prospective cohort study was conducted in California, Florida, and Illinois. Participants included elderly (65-89 years) women identified from Medicare claims as having had incident invasive breast cancer surgery in 2003. Patient, tumor, treatment, and surgeon characteristics were examined. Type of axillary surgery performed. Of 1703 women who received treatment by 863 surgeons, 56.4% underwent an initial SLNB, 37.2% initial axillary lymph node dissection, and 6.3% no axillary surgery. The median annual surgeon Medicare volume of breast cancer cases was 6.0 (range, 1.5-57.0); the median surgeon percentage of breast cancer cases was 4.5% (range, 0.4%-100.0%). After multivariable adjustment of patient and surgeon factors, women operated on by surgeons with higher volumes and percentages of breast cancer cases had a higher likelihood of undergoing SLNB. Specifically, women were most likely to undergo SLNB if the operation was performed by high-volume surgeons (regardless of percentage) or by lower-volume surgeons with a high percentage of breast cancer cases. In addition, membership in the American Society of Breast Surgeons (odds ratio, 1.98; 95% CI, 1.51-2.60) and Society of Surgical Oncology (1.59; 1.09-2.30) were independent predictors of women undergoing an initial SLNB. Patients who receive treatment from surgeons with more experience with and focus on breast cancer are significantly more likely to undergo SLNB, highlighting the importance of receiving initial treatment by specialized providers. Factors relating to specialization in a particular area, including our novel surgeon percentage measure, require further investigation as potential indicators of quality of care.

Clinicopathologic Characteristics and Prognosis of Breast Cancer Patients Associated with Pregnancy and Lactation: Analysis of Case‐Control Study in Japan

PubMed Central

Ishida, Tsunehiro; Kasumi, Fujio; Sakamoto, Goi; Makita, Masujiro; Tominaga, Takeshi; Simozuma, Kohjiro; Enomoto, Kohji; Fujiwara, Kiyoshi; Nanasawa, Takeshi; Fukutomi, Takashi; Hirota, Teruyuki; Fukuda, Mamoru; Miura, Shigeto; Koyama, Hiroki; Inaji, Hideo; Sonoo, Hiroshi

1992-01-01

Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation were clarified by means of a case‐control study of matched non‐pregnant and non‐lactating patients with breast cancer. From 18 institutions in Japan, a total of 192 subjects with breast cancer diagnosed during pregnancy (72 cases) and lactation (120 cases) were collected between 1970 and 1988, accounting for 0.76% of all breast cancer patients. The duration of symptoms was longer and tumor size was larger in the study subjects. Although the disease‐free interval was longer than that in the control patients, the survival time was shorter. There was no characteristic difference in histologic type. Vascular invasion and lymph node metastasis were found more frequently in the subjects. The positive rates of estrogen receptor and progesterone receptor were lower in the subjects. The 5‐ and 10‐year survival rates of the study patients were 65% and 55%, respectively, and these survivals were significantly lower than those of the control (P < 0.001). The survival rates were poorer in the subjects, in accordance with stage and lymph node metastasis. The results suggest that most of the patients with breast cancer diagnosed during pregnancy and lactation are in a more advanced stage because of a delay in detection and diagnosis, and hence have unfavorable prognosis. Therefore, it is important to diagnose and treat early for improvement of prognosis in patients with breast cancer during pregnancy and lactation. PMID:1483929

Axillary lymph node micrometastases in invasive breast cancer: national figures on incidence and overall survival.

PubMed

Grabau, D; Jensen, M B; Rank, F; Blichert-Toft, M

2007-07-01

The purpose of this study was to estimate the incidence and prognostic value of axillary lymph node micrometastases (Nmic) of 2 mm or less in breast carcinomas. Results are based on data from the Danish Breast Cancer Cooperative Group (DBCG). The study was carried out as a nationwide, population-based trial with a study series consisting of 6,959 women under 75 years of age registered in the national DBCG data base from 1 January 1990 to 31 October 1994. All patients had contracted operable primary breast carcinoma, stage I-III, classified according to the TNM system as T1-T3, N0-N1, M0. Women with four or more metastatic axillary lymph nodes were excluded. All patients were treated systematically according to approved national guidelines and treatment protocols. Metastases were recognized microscopically on haematoxylin and eosin-stained sections. In case of doubt immunohistochemical staining for cytokeratin was performed. There was no serial sectioning. Micrometastases were tumour deposits of 2 mm or smaller, and accordingly included deposits of 0.2 mm and smaller. With a median observation time of 10 years and 2 months, women with Nmic (N=427) experienced a significantly worse overall survival (OS) compared with node-negative (Nneg) women (N=4,767) (relative risk (RR)=1.20, 95% CI: 1.01-1.43), irrespective of menopausal status. Women with macrometastases (Nmac) (N=1,765) had significantly worse final outcome than women with Nmic (RR=1.54, 95% CI: 1.29-1.85), irrespective of menopausal status. Multivariate analysis adjusted for patient-, histopathologic-, and loco-regional therapeutic variables showed that cases with Nmic had a significantly higher risk of death relative to Nneg cases (adjusted RR=1.49, 95% CI: 1.18-1.90). Interaction analysis showed that the number of nodes examined had a significant impact on adjusted relative risk of death according to axillary status. Furthermore, the number of nodes involved significantly influenced adjusted risk of death in the Nmic compared to the Nmac series. In conclusion, the results of the present study revealed worse final outcome in women with Nmic compared with Nneg, where all Nmic cases received adjuvant systemic treatment. Interaction analysis showed that the number of retrieved axillary nodes and the number of affected nodes had a different influence on survival related to axillary status. The different risk pattern in Nmic vs Nmac patients indicates that Nmic cases do not show the traditional risk pattern as revealed by the Nmac cases, in which increasing number of positive nodes is associated with an orderly increasing adjusted RR.

NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude) Mice

PubMed Central

Puchalapalli, Madhavi; Zeng, Xianke; Mu, Liang; Anderson, Aubree; Hix Glickman, Laura; Zhang, Ming; Sayyad, Megan R.; Mosticone Wangensteen, Sierra; Clevenger, Charles V.; Koblinski, Jennifer E.

2016-01-01

Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D) and negative (MDA-MB-231, SUM1315, and CN34BrM) human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes) was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model. PMID:27662655

Accurate evaluation of axillary sentinel lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid in breast cancer: a preliminary clinical trial.

PubMed

Matsuzawa, Fumihiko; Omoto, Kiyoka; Einama, Takahiro; Abe, Hironori; Suzuki, Takashi; Hamaguchi, Jun; Kaga, Terumi; Sato, Mami; Oomura, Masako; Takata, Yumiko; Fujibe, Ayako; Takeda, Chie; Tamura, Etsuya; Taketomi, Akinobu; Kyuno, Kenichi

2015-01-01

Breast cancer is the most common type of cancer in women. The 5-year survival rate in patients with breast cancer ranges from 74 to 82 %. Sentinel lymph node biopsy has become an alternative to axillary lymph node dissection for nodal staging. We evaluated the detection of the sentinel lymph node and metastasis of the lymph node using contrast enhanced ultrasonography with Sonazoid. Between December 2013 and May 2014, 32 patients with operable breast cancer were enrolled in this study. We evaluated the detection of axillary sentinel lymph nodes and the evaluation of axillary lymph nodes metastasis using contrast enhanced computed tomography, color Doppler ultrasonography and contrast enhanced ultrasonography with Sonazoid. All the sentinel lymph nodes were identified, and the sentinel lymph nodes detected by contrast enhanced ultrasonography with Sonazoid corresponded with those detected by computed tomography lymphography and indigo carmine method. The detection of metastasis based on contrast enhanced computed tomography were sensitivity 20.0 %, specificity 88.2 %, PPV 60.0 %, NPV 55.6 %, accuracy 56.3 %. Based on color Doppler ultrasonography, the results were sensitivity 36.4 %, specificity 95.2 %, PPV 80.0 %, NPV 74.1 %, accuracy 75.0 %. Based on contrast enhanced ultrasonography with Sonazoid, the results were sensitivity 81.8 %, specificity 95.2 %, PPV 90.0 %, NPV 90.9 %, accuracy 90.6 %. The results suggested that contrast enhanced ultrasonography with Sonazoid was the most accurate among the evaluations of these modalities. In the future, we believe that our method would take the place of conventional sentinel lymph node biopsy for an axillary staging method.

Surgeon Training, Protocol Compliance, and Technical Outcomes From Breast Cancer Sentinel Lymph Node Randomized Trial

PubMed Central

Ashikaga, Takamaru; Harlow, Seth P.; Skelly, Joan M.; Julian, Thomas B.; Brown, Ann M.; Weaver, Donald L.; Wolmark, Norman

2009-01-01

Background The National Surgical Adjuvant Breast and Bowel Project B-32 trial was designed to determine whether sentinel lymph node resection can achieve the same therapeutic outcomes as axillary lymph node resection but with fewer side effects and is one of the most carefully controlled and monitored randomized trials in the field of surgical oncology. We evaluated the relationship of surgeon trial preparation, protocol compliance audit, and technical outcomes. Methods Preparation for this trial included a protocol manual, a site visit with key participants, an intraoperative session with the surgeon, and prerandomization documentation of protocol compliance. Training categories included surgeons who submitted material on five prerandomization surgeries and were trained by a core trainer (category 1) or by a site trainer (category 2). An expedited group (category 3) included surgeons with extensive experience who submitted material on one prerandomization surgery. At completion of training, surgeons could accrue patients. Two hundred twenty-four surgeons enrolled 4994 patients with breast cancer and were audited for 94 specific items in the following four categories: procedural, operative note, pathology report, and data entry. The relationship of training method; protocol compliance performance audit; and the technical outcomes of the sentinel lymph node resection rate, false-negative rate, and number of sentinel lymph nodes removed was determined. All statistical tests were two-sided. Results The overall sentinel lymph node resection success rate was 96.9% (95% confidence interval [CI] = 96.4% to 97.4%), and the overall false-negative rate was 9.5% (95% CI = 7.4% to 12.0%), with no statistical differences between training methods. Overall audit outcomes were excellent in all four categories. For all three training groups combined, a statistically significant positive association was observed between surgeons’ average number of procedural errors and their false-negative rate (ρ = +0.188, P = .021). Conclusions All three training methods resulted in uniform and high overall sentinel lymph node resection rates. Subgroup analyses identified some variation in false-negative rates that were related to audited outcome performance measures. PMID:19704072

Deep radio imaging of the UKIDSS Ultra Deep Survey field : the nature of the faint radio population, and the star-formation history of the Universe

NASA Astrophysics Data System (ADS)

Arumugam, Vinodiran

2013-08-01

Breast cancer remains a significant cause of morbidity and mortality. Assessment of the axillary lymph nodes is part of the staging of the disease. Advances in surgical management of breast cancer have seen a move towards intra-operative lymph node assessment that facilitates an immediate axillary clearance if it is indicated. Raman spectroscopy, a technique based on the inelastic scattering of light, has previously been shown to be capable of differentiating between normal and malignant tissue. These results, based on the biochemical composition of the tissue, potentially allow for this technique to be utilised in this clinical context. The aim of this study was to evaluate the facility of Raman spectroscopy to both assess axillary lymph node tissue within the theatre setting and to achieve results that were comparable to other intra-operative techniques within a clinically relevant time frame. Initial experiments demonstrated that these aims were feasible within the context of both the theatre environment and current surgical techniques. A laboratory based feasibility study involving 17 patients and 38 lymph node samples achieved sensivities and specificities of >90% in unsupervised testing. 339 lymph node samples from 66 patients were subsequently assessed within the theatre environment. Chemometric analysis of this data demonstrated sensitivities of up to 94% and specificities of up to 99% in unsupervised testing. The best results were achieved when comparing negative nodes from N0 patients and nodes containing macrometastases. Spectral analysis revealed increased levels of lipid in the negative nodes and increased DNA and protein levels in the positive nodes. Further studies highlighted the reproducibility of these results using different equipment, users and time from excision. This study uses Raman spectroscopy for the first time in an operating theatre and demonstrates that the results obtained, in real-time, are comparable, if not superior, to current intra-operative techniques of lymph nodes assessment.

Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors.

PubMed

Tang, Gong; Cuzick, Jack; Costantino, Joseph P; Dowsett, Mitch; Forbes, John F; Crager, Michael; Mamounas, Eleftherios P; Shak, Steven; Wolmark, Norman

2011-11-20

The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors

PubMed Central

Tang, Gong; Cuzick, Jack; Costantino, Joseph P.; Dowsett, Mitch; Forbes, John F.; Crager, Michael; Mamounas, Eleftherios P.; Shak, Steven; Wolmark, Norman

2011-01-01

Purpose The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) –positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. Patients and Methods From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. Results RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). Conclusion RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit. PMID:22010013

Breast Cancer Surgery

MedlinePlus

FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT.

PubMed

Liu, Xue; Chen, Qian; Hu, Xu-Gang; Zhang, Xian-Chao; Fu, Ti-Wei; Liu, Qing; Liang, Yan; Zhao, Xi-Long; Zhang, Xia; Ping, Yi-Fang; Bian, Xiu-Wu

2016-10-01

Metastasis is a complicated, multistep process and remains the major cause of cancer-related mortality. Exploring the molecular mechanisms underlying tumor metastasis is crucial for development of new strategies for cancer prevention and treatment. In this study, we found that protein tyrosine phosphatase 1B (PTP1B) promoted breast cancer metastasis by regulating phosphatase and tensin homolog (PTEN) but not epithelial-mesenchymal transition (EMT). By detecting PTP1B expression of the specimens from 128 breast cancer cases, we found that the level of PTP1B was higher in breast cancer tissues than the corresponding adjacent normal tissues. Notably, PTP1B was positively associated with lymph node metastasis (LNM) and estrogen receptor (ER) status. In vitro, disturbing PTP1B expression obviously attenuated cell migration and invasion. On the contrary, PTP1B overexpression significantly increased migration and invasion of breast cancer cells. Mechanistically, PTP1B knockdown upregulated PTEN, accompanied with an abatement of AKT phosphorylation and the expression of matrix metalloproteinase 2 (MMP2) and MMP7. Conversely, forced expression of PTP1B reduced PTEN and increased AKT phosphorylation as well as the expression of MMP2 and MMP7. Notably, neither EMT nor stemness of breast cancer cells was regulated by PTP1B. We also found that PTP1B acted as an independent prognostic factor and predicted poor prognosis in ER-positive breast cancer patients. Taken together, our findings provide advantageous evidence for the development of PTP1B as a potential therapeutic target for breast cancer, especially for ER-positive breast cancer patients.

Role of gastrin-releasing peptides in breast cancer metastasis.

PubMed

Ni, Chunsheng; Zhao, Xiulan; Sun, Tao; Liu, Yanrong; Gu, Qiang; Sun, Baocun

2012-12-01

The gastrin-releasing peptide, which is an unfolded protein response regulator and functions as a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum, is a regulatory human peptide that elicits gastrin release and regulates gastric acid secretion and enteric motor function. It has been shown to exhibit mitogenic activity in small cell lung cancer and plays a role in a lot of other human cancers including tumors in colon, stomach, pancreas, breast, and prostate. This study investigated the gastrin-releasing peptide expression in breast cancer to demonstrate the role of this biomarker in breast cancer metastasis. Gastrin-releasing peptide was analyzed in breast cancer tissue microarray specimens, including 200 primary breast cancer specimens and the corresponding lymph nodes from the same patients, through immunohistochemistry. The effect of gastrin-releasing peptide on the invasion ability of MCF-7 cells was evaluated using transwell assays. Gastrin-releasing peptide was highly expressed in breast cancer patients with lymph node metastasis. Besides, among the patients with lymph node metastasis, the ones with higher expression of gastrin-releasing peptide had shorter survival time. Overexpression of gastrin-releasing peptide significantly enhanced cell invasiveness. Conversely, a knockdown of gastrin-releasing peptide through the short hairpin RNA approach remarkably reduced MCF-7 cell invasion. Gastrin-releasing peptide expression may be associated with lymph node metastasis and may be used as an indicator of undesirable prognosis in patients with breast cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

A comparison of the diagnostic accuracy of magnetic resonance imaging to axillary ultrasound in the detection of axillary nodal metastases in newly diagnosed breast cancer.

PubMed

Assing, Matthew A; Patel, Bhavika K; Karamsadkar, Neel; Weinfurtner, Jared; Usmani, Omar; Kiluk, John V; Drukteinis, Jennifer S

2017-11-01

Patients with a diagnosis of invasive breast cancer are increasingly undergoing breast magnetic resonance imaging (MRI) for preoperative staging including evaluation of axillary lymph node metastases (ALNM). This retrospective study aims to evaluate the utility of adding axillary ultrasound (AUS) in the preoperative setting when an MRI is planned or has already been performed. This IRB approved, HIPAA compliant study reviewed a total of 271 patients with a new diagnosis of invasive breast cancer at a single institution, between June 1, 2010 and June 30, 2013. The study included patients who received both AUS and MRI for preoperative staging. Data were divided into two cohorts, patients who underwent MRI prior to AUS and those who underwent AUS prior to MRI. AUS and MRI reports were categorized according to BI-RADS criteria as "suspicious" or "not suspicious" for ALNM. In the setting of a negative MRI and subsequent positive AUS, only one out of 25 cases (4%) were positive for metastases after correlating with histologic pathology. MRI detected metastatic disease in four out of 27 (15%) patients who had false-negative AUS performed prior to MRI. Our results indicate the addition of AUS after preoperative MRI does not contribute significantly to increased detection of missed disease. MRI could serve as the initial staging imaging method of the axilla in the setting that AUS is not initially performed and may be valuable in identification of lymph nodes not identified on AUS. © 2017 Wiley Periodicals, Inc.

Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

Cancer.gov

Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

Clinical significance of Mena and Her-2 expression in breast cancer.

PubMed

Du, J W; Xu, K Y; Fang, L Y; Qi, X L

2012-01-01

The aim of this study was to determine the expression patterns of Mena and Her-2 in breast cancer tissues and to explore their clinical significance and correlation with clinicopathological parameters. The expression of Mena and Her-2 was detected in 40 breast cancer tissues and 14 normal breast tissues by immunohistochemistry, and the relationship of Mena and Her-2 expression with clinicopathological parameters was analyzed. Both Mena (70%) and Her-2 (40%) were more commonly expressed in breast cancer than in normal breast tissue (7.1%, 0%, respectively; p < 0.05); further, Mena and Her-2 expression in breast cancer were positively correlated (r = 0.530, p < 0.05). In comparing expression with clinicopathological parameters of tumor samples, Mena and Her-2 were both associated with axillary lymph node metastasis and TNM stage (p < 0.05), but not with patient age or pathological type. Mena and Her-2 are related to the malignancy degree and metastasis of breast cancer, and thus may play a coordinating role in the occurrence and progression of breast cancer.

Meta-analysis of aberrant lymphatic drainage in recurrent breast cancer.

PubMed

Ahmed, M; Baker, R; Rubio, I T

2016-11-01

Sentinel node biopsy (SNB) in recurrent breast cancer offers targeted axillary staging compared with axillary lymph node dissection (ALND) or no treatment. The evidence for lymphatic mapping in recurrent breast cancer is reviewed, focusing on aberrant drainage and its implications for patient management. A meta-analysis of studies evaluating lymphatic mapping in recurrent breast cancer was performed. Outcomes included sentinel node identification, aberrant lymphatic pathways and metastatic node rates in aberrant drainage and ipsilateral axilla. Pooled odds ratios (ORs) and 95 per cent confidence intervals (c.i.) were estimated using fixed-effect analyses, or random-effects analyses in the event of statistically significant heterogeneity. Seven studies reported data on lymphatic mapping in 1053 patients with recurrent breast cancer. The intraoperative sentinel node identification rate was 59·6 (95 per cent c.i. 56·7 to 62·6) per cent, and significantly greater when the original axillary surgery was SNB compared with ALND (OR 2·97, 95 per cent c.i. 1·66 to 5·32). The rate of aberrant lymphatic drainage identification was 25·7 (23·0 to 28·3) per cent, and significantly greater when the original axillary surgery was ALND (OR 0·27, 0·19 to 0·38). The metastatic sentinel node rate was 10·4 (8·6 to 12·3) per cent, and a significantly greater metastatic nodal burden was identified in the ipsilateral axilla (OR 6·31, 1·03 to 38·79). Lymphatic mapping is feasible in recurrent breast cancer. It avoids ALND in over 50 per cent of patients who have undergone SNB, and allows the 4 per cent of patients with metastatically involved aberrant nodes to receive targeted surgical and adjuvant therapies. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Effect of young age, positive margins, and triple negative status on disease recurrence after breast conserving therapy

PubMed Central

Sakulchairungreung, Bundit; Chirappapha, Prakasit; Suvikapakornkul, Ronnarat; Wasuthit, Yodying; Sukarayothin, Thongchai; Leesombatpaiboon, Montchai; Kongdan, Youwanush

2016-01-01

Background To determine the risk factors for disease recurrence after breast conserving therapy (BCT) for breast cancer in a group of South-East Asian women. Methods Medical and pathological records of women who underwent BCT during the 10-year period from 2001 to 2010 were reviewed. Data collected included age ≤35 years defined as the young, type of operation, pathological data, hormonal receptor (HR) status, human epidermal growth factor receptor-2 (HER-2) expression status, and surgical margin status. Data on adjuvant therapy were also collected. Main outcomes were overall breast cancer recurrence, locoregional, and distant recurrence. Risk factors for each type of recurrence were identified using Cox proportional hazards regression models. Results There were 294 BCTs in 290 patients during the study period. The overwhelming majority (91%) had early stage (stages I-II) breast cancers. Young age patients constituted 9% of all patients, and triple negative cancers (HR negative and HER-2 negative) were seen in 19%. Involved margins on initial surgery were found in 9% of cases, and after reoperation, only 2% had involved margins. After a median follow-up of 50 months, and a maximum follow-up of 135 months, there were 30 recurrences and 6 deaths. Of the 30 recurrences, 19 included locoregional, 20 included distant, and 13 had in-breast recurrences. The disease-free survival at 10 years was 82.5% (95% CI: 74.8% to 88.1%), and the cumulative in-breast recurrence was 9.3% (95% CI: 4.9% to 17.2%) at 10 years. Multivariable Cox regression analysis revealed that young age, larger tumor size, involved margins, and no breast irradiation were associated with higher risk of locoregional recurrence. Triple negative status, larger tumor size, more positive nodes, and involved margins were associated with higher risk of distant recurrence. Conclusions We found young age to be a significant prognosticator of locoregional recurrence, and triple negative status of distant recurrence. Involved surgical margin status was associated with both recurrences. Tumor size was associated with both recurrences, and axillary lymph node metastasis was associated with distant recurrence. PMID:26855904

The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

PubMed

Topps, A; Clay, V; Absar, M; Howe, M; Lim, Y; Johnson, R; Bundred, N

2014-07-01

Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nanoparticle-Enhanced MRI to Evaluate Radiation Delivery to the Regional Lymphatics for Patients With Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, Shannon M., E-mail: smacdonald@partners.or; Harisinghani, Mukesh G.; Katkar, Amol

2010-07-15

Purpose: At present, radiation (RT) fields are based largely, and often solely, on bony anatomy. Recent efforts have been taken to better define lymphatic regions for RT planning. Lymphotrophic nanoparticle-enhanced MRI (LN-MRI) allows for accurate identification of malignant and benign lymph nodes. We sought to evaluate RT delivery to lymphatics for breast cancer using LN-MRI. Methods and Materials: Twenty-three patients with breast cancer underwent LN-MRI. MRIs were anatomically registered to a reference CT; benign and malignant lymph nodes were contoured. Standard RT fields were planned and dose calculated to prescribe 45-50 Gy. Lymphatic regions were contoured on CT. Coverage ofmore » LN-MRI lymph nodes by RT fields and contoured lymphatics were assessed. Results: Eighty-one percent of all lymph nodes defined by LN-MRI were covered by the 45-Gy isodose line; 82% of malignant and 79% of benign. The 50-Gy isodose line only encompassed 60% of LN-MRI defined lymph nodes-64% of malignant and 59% of benign. For nodal volumes contoured in the absence of a margin, 86% of actual lymph nodes were within contoured volumes. When a 5-mm expansion was added, 99% were included. Conclusions: LN-MRI is a useful tool to delineate the location of breast regional lymphatics. These results suggest less than desired coverage of lymph nodes using standard RT fields and that a margin may be advisable when defining nodal volumes by CT. The use of IMRT and RT in lieu of surgery makes accurate definition of the location of breast regional lymphatics of paramount importance.« less

The impact of previous para-areolar incision in the upper outer quadrant of the breast on the localization of the sentinel lymph node in a canine model

PubMed Central

Vasques, Paulo Henrique Diógenes; Pinheiro, Luiz Gonzaga Porto; de Meneses e Silva, João Marcos; de Moura Torres-de-Melo, José Ricardo; Pinheiro, Karine Bessa Porto; Rocha, João Ivo Xavier

2011-01-01

OBJECTIVES: This paper discusses the influence of a para-areolar incision in the upper outer quadrant of the breast on the location of the sentinel lymph node in a canine model. METHODS: The sentinel lymph node was marked with technetium-99, which was injected into the subareolar skin of the cranial breast. After the marker had migrated to the axilla, an arcuate para-areolar incision was performed 2 cm from the nipple in the upper outer quadrant. Patent blue dye was then injected above the upper border of the incision. At the marked site, an axillary incision was made, and the sentinel lymph node was identified by gamma probe and/or by direct visualization of the dye. The agreement between the two injection sites and the two sentinel lymph node identification methods was determined. Our sample group consisted of 40 cranial breasts of 23 adult females of the species Canis familiaris. The data were analyzed by using the McNemar test and by determining the kappa agreement coefficient. RESULT: Our findings showed that in 95% of the breasts, the sentinel lymph node was identified by the injection of technetium-99 m into the subareolar region, and in 82% of the cases, the sentinel lymph node was identified by the injection of patent blue dye above the upper border of the incision. The methods agreed 82% of the time. CONCLUSIONS: Previous para-areolar incisions in the upper outer quadrant did not interfere significantly with the biopsy when the dye was injected above the upper border of the incision. PMID:21915493

Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response.

PubMed

Díaz-Expósito, R; Martí-Bonmatí, L; Burgués, O; Casáns-Tormo, I; Bermejo-de Las Heras, B; Julve-Parreño, A; Caballero-Garate, A

Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, p<0.01). The scintigraphic detection of the sentinel node after intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Access to care issues adversely affect breast cancer patients in Mexico: oncologists' perspective.

PubMed

Chavarri-Guerra, Yanin; St Louis, Jessica; Liedke, Pedro E R; Symecko, Heather; Villarreal-Garza, Cynthia; Mohar, Alejandro; Finkelstein, Dianne M; Goss, Paul E

2014-09-09

Despite recently implemented access to care programs, Mexican breast cancer (BC) mortality rates remain substantially above those in the US. We conducted a survey among Mexican Oncologists to determine whether practice patterns may be responsible for these differences. A web-based survey was sent to 851 oncologists across Mexico using the Vanderbilt University REDCap database. Analyses of outcomes are reported using exact and binomial confidence bounds and tests. 138 participants (18.6% of those surveyed) from the National capital and 26 Mexican states, responded. Respondents reported that 58% of newly diagnosed BC patients present with stage III-IV disease; 63% undergo mastectomy, 52% axillary lymph node dissection (ALND) and 48% sentinel lymph node biopsy (SLNB). Chemotherapy is recommended for tumors > 1 cm (89%), positive nodes (86.5%), triple-negative (TN) (80%) and HER2 positive tumors (58%). Trastuzumab is prescribed in 54.3% and 77.5% for HER2 < 1 cm and > 1 cm tumors, respectively. Tamoxifen is indicated for premenopausal hormone receptor (HR) positive tumors in 86.5% of cases and aromatase inhibitors (AI's) for postmenopausal in 86%. 24% of physicians reported treatment limitations, due to delayed or incomplete pathology reports and delayed or limited access to medications. Even though access to care programs have been recently applied nationwide, women commonly present with advanced BC, leading to increased rates of mastectomy and ALND. Mexican physicians are dissatisfied with access to appropriate medical care. Our survey detects specific barriers that may impact BC outcomes in Mexico and warrant further investigation.

Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.

PubMed

Chlebowski, Rowan T; Anderson, Garnet L; Gass, Margery; Lane, Dorothy S; Aragaki, Aaron K; Kuller, Lewis H; Manson, JoAnn E; Stefanick, Marcia L; Ockene, Judith; Sarto, Gloria E; Johnson, Karen C; Wactawski-Wende, Jean; Ravdin, Peter M; Schenken, Robert; Hendrix, Susan L; Rajkovic, Aleksandar; Rohan, Thomas E; Yasmeen, Shagufta; Prentice, Ross L

2010-10-20

In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants. Invasive breast cancer incidence and breast cancer mortality. In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. clinicaltrials.gov Identifier: NCT00000611.

Decline in Frozen Section Diagnosis for Axillary Sentinel Lymph Nodes as a Result of the American College of Surgeons Oncology Group Z0011 Trial.

PubMed

Bishop, Julie Anne; Sun, Jihong; Ajkay, Nicolas; Sanders, Mary Ann G

2016-08-01

-Results of the American College of Surgeons Oncology Group Z0011 trial showed that patients with early-stage breast cancer and limited sentinel node metastasis treated with breast conservation and systemic therapy did not benefit from axillary lymph node dissection. Subsequently, most pathology departments have likely seen a decrease in frozen section diagnosis of sentinel lymph nodes. -To determine the effect of the Z0011 trial on pathology practice and to examine the utility of intraoperative sentinel lymph node evaluation for this subset of patients. -Pathology reports from cases of primary breast cancer that met Z0011 clinical criteria and were initially treated with lumpectomy and sentinel lymph node biopsy from 2009 to 2015 were collected. Clinicopathologic data were recorded. -Sentinel lymph node biopsies sent for frozen section diagnosis occurred in 22 of 22 cases (100%) in 2009 and 15 of 22 cases (68%) in 2010 during the pre-Z0011 years, and in 3 of 151 cases (2%) collected in 2011 through 2015, considered to be post-Z0011 years. Of the 151 post-Z0011 cases, 28 (19%) had sentinel lymph nodes with metastasis, and 147 (97%) were spared axillary lymph node dissection. -Following Z0011, intraoperative sentinel lymph node evaluation has significantly decreased at our institution. Prior to surgery, all patients had clinically node-negative disease. After sentinel lymph node evaluation, 97% (147 of 151) of the patients were spared axillary lymph node dissection. Therefore, routine frozen section diagnosis for sentinel lymph node biopsies can be avoided in these patients.

Anthracycline Use for Early Stage Breast Cancer in the Modern Era: a Review.

PubMed

Jasra, Sakshi; Anampa, Jesus

2018-05-11

Anthracycline-based regimens have been an important treatment component for patients with breast cancer. As demonstrated in the last Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis, anthracycline-based regimens decrease breast cancer mortality by 20-30%. Anthracycline toxicities include the rare-but potential morbid-cardiotoxicity or leukemogenic effect, and the almost universal-but very distressing-alopecia. Due to potential toxicities, and large number of patients being exposed, several worldwide trials have re-examined the role of anthracycline-based regimens in the management of breast cancer. Current literature supports that anthracyclines are not required for all patients with breast cancer and should be avoided in those with high cardiac risk. Recent results from the ABC trials suggest that anthracyclines should not be spared for patients with triple negative breast cancer (regardless of axillary node involvement) or HER2-/ER+ with significant node involvement. Based on current literature, for HER2-negative patients with low-risk breast cancer, anthracyclines could be spared with regimens such as cyclophosphamide, methotrexate, and fluorouracil (CMF) or docetaxel and cyclophosphamide (TC). Patients with intermediate or high-risk breast cancer should be considered for anthracycline-based regimens based on other factors such as age, comorbidities, tumor grade, lymphovascular invasion, and genomic profiling. Patients with HER2-positive breast cancer with low risk could be treated with paclitaxel and trastuzumab. For the remaining patients with HER2 overexpression, while docetaxel, carboplatin, and trastuzumab (TCH) has demonstrated to improve disease-free survival (DFS), anthracycline-containing regimens should be discussed, especially for those with very high-risk breast cancer. Although several biomarkers, such as topoisomerase II (TOP2A) and chromosome 17 centromeric duplication (Ch17CEP) have been proposed to predict benefit from anthracycline regimens, further research is required to delineate their proper utility in the clinical setting.

[Relationship between SLP-2 expression and prognosis in laryngeal squamous cell carcinoma and mammary invasive carcinoma].

PubMed

Cao, Wen-feng; Zhang, Li-yong; Zhang, Bin; Liu, Ming-bo; Liu, Zhi-hua; Sun, Bao-cun

2010-05-01

To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis. RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed. LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors. A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.

Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

NASA Astrophysics Data System (ADS)

Zhang, Jialing; Feider, Clara L.; Nagi, Chandandeep; Yu, Wendong; Carter, Stacey A.; Suliburk, James; Cao, Hop S. Tran; Eberlin, Livia S.

2017-06-01

Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed. [Figure not available: see fulltext.

[Economic assessment of the routine use of Oncotype DX® assay for early breast cancer in Franche-Comte region].

PubMed

Nerich, Virginie; Curtit, Elsa; Bazan, Fernando; Montcuquet, Philippe; Villanueva, Cristian; Chaigneau, Loïc; Cals, Laurent; Méneveau, Nathalie; Dobi, Erion; Altmotlak, Hamadi; Algros, Marie-Paule; Choulot, Marie-Jeanne; Nallet, Gilles; Limat, Samuel; Mansion, Sylvie; Pivot, Xavier

2014-01-01

Oncotype DX® has been validated as quantifying the likelihood of distant recurrence at 10 years and overall chemotherapy benefit in patients with estrogen-receptor-positive and HER-2-negative early breast cancer. In 2012, this genomic signature was routinely available for patients in Franche-Comté, France. Patients eligible for Oncotype DX(®) testing had a ER-positive, HER-2-négative early breast cancer with a nodal involvement limited to 0 or 1 positive-node without extracapsular spread; an adjuvant chemotherapy was indicated based on usual prognostic factors. The aim was to assess the economic impact of Oncotype DX(®) testing in a French region. A cost-minimisation analysis from the French Public Healthcare System perspective was performed. The availability of Oncotype DX(®) in Franche-Comté, France, and its use in clinical routine allowed a decrease of 73 % of adjuvant chemotherapy without increase of the cost of the patients' management and with a potential reduction of the cost for the French Public Healthcare System. This strategy was successful and may allow the reimbursement of this test in France for patients with early breast cancer.

Toxoplasma lymphadenitis mimicking malign axillary lymphadenopathy of a left breast mass.

PubMed

Yildirim, Ali Cihat; Bostanci, Hasan; Yilmaz, Engin Deniz; Kutluer, Nizamettin; Kargici, Hulagu

2013-06-01

Toxoplasmosis is an infection caused by the intracellular parasite, Toxoplasma gondii. Immunocompetent persons with primary infection are usually asymptomatic, but latent infection can persist for the life of the host. There is a risk of reactivating infection at a later time should the individual become immunocompromised, even if infection was asymptomatic or only mildly symptomatic initially. Axillary lymph nodes receive 85% of the lymphatic drainage from the breast. Lymph node metastases are relatively common even with invasive breast cancers ≤1 cm in size. Here, we report a case of toxoplasma lymphadenitis in a female adult patient mimicking a malign breast lymphadenopathy of a left breast mass.

Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

PubMed

Shek, L L; Godolphin, W; Spinelli, J J

1987-12-01

The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation.

Arm lymphoedema and upper limb impairments in sentinel node-negative breast cancer patients: A one year follow-up study.

PubMed

De Groef, An; Van Kampen, Marijke; Tieto, Elena; Schönweger, Petra; Christiaens, Marie-Rose; Neven, Patrick; Geraerts, Inge; Gebruers, Nick; Devoogdt, Nele

2016-10-01

The aim of this study is (1) to investigate the prevalence rate of arm lymphedema, pain, impaired shoulder range of motion, strength and shoulder function one year after a sentinel lymph node biopsy (SLNB) for breast cancer and (2) to determine predictive factors for these complications. A longitudinal study was performed. One hundred patients with a sentinel-lymph node negative breast cancer were included. All patients were measured before surgery and one year after. Arm lymphedema was measured with the perimeter, pain with the Visual Analogue Scale, shoulder range of motion with an inclinometer, strength with a handheld dynamometer and shoulder function with the Disability of Arm, Shoulder and Hand questionnaire. Patient-, breast cancer- and treatment-related variables were recorded. One year after surgery 8% of sentinel node-negative breast cancer patients had developed arm lymphedema. Fifty percent of patients had pain, 30% had an impaired shoulder range of motion, 8% had a decreased handgrip strength and 49% had an impaired shoulder function. Pain, shoulder range of motion, strength and shoulder dysfunctions changed significantly over one year (p < 0.001). Higher Body Mass Index is a predictive variable for shoulder dysfunctions one year post-SLNB. Prevalence rate of lymphedema and other upper limb impairments may not be underestimated after SLNB. Pain, shoulder range of motion, handgrip strength and shoulder function change significantly up to one year compared to preoperative values in sentinel node-negative breast cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Breast Cancer Metastases to the Gastrointestinal Tract Presenting with Anemia and Intra-abdominal Bleed.

PubMed

Khan, Idrees; Malik, Rehan; Khan, Amina; Assad, Salman; Zahid, Mehr; Sohail, Muhammad Saad; Yasin, Faizan; Qavi, Ahmed H

2017-07-06

Signet ring adenocarcinoma of the breast with synchronous metastasis to the gastrointestinal (GI) tract is a rare occurrence, typically presenting with abdominal pain, dyspepsia, or GI bleed. We report a case of metastatic breast cancer presenting with a complaint of anemia. A further diagnostic evaluation revealed generalized lymphadenopathy, nodular thickening of the urinary bladder wall, bone lesions, and enlarged pancreas. Biopsies from the lymph nodes, pancreatic biopsy, and bladder nodule all revealed a signet cell carcinoma. An upper and lower GI endoscopy revealed multiple ulcerated gastric mucosal nodules and polypoid folds in the cecum and proximal ascending colon; the biopsies from these lesions were also positive for signet ring cell adenocarcinoma.

Variations in the management of the axilla in screen-detected ductal carcinoma in situ: evidence from the UK NHS breast screening programme audit of screen detected DCIS.

PubMed

Nicholson, S; Hanby, A; Clements, K; Kearins, O; Lawrence, G; Dodwell, D; Bishop, H; Thompson, A

2015-01-01

The diagnosis and surgical management of screen-detected Ductal Carcinoma In Situ (DCIS) remains controversial including a range of axillary approaches and consequent morbidity. This study examined the management of the axilla in all patients with DCIS presenting through the United Kingdom National Health Service Breast Screening Programme (UK NHS BSP). Retrospective analysis of the UK NHS BSP identified 26,696 women initially diagnosed with DCIS over the 8 years 1 April 2003-31 March 2011. The final breast pathology of these women was upgraded to invasive ductal cancer in 5564 (20.8%) women or micro-invasive cancer in 1031 (3.9%) women. At first operation, 5290 (26.3%) of the 20,094 women who had a final post-operative diagnosis of DCIS only underwent axillary surgery (72.4% at the time of mastectomy, 23.8% breast conservation surgery, 3.8% axillary surgery alone). Performance of axillary surgery reflected increasing tumour size, micro-invasion or increasing nuclear grade for the final diagnosis of DCIS. More extensive nodal surgery was performed in those undergoing mastectomy; 10.8% of women had more than 8 nodes removed. Overall, 12.0% of women with invasive cancer, 1.7% with micro-invasion, and 0.2% with DCIS alone, were ultimately node positive. Improved pre-operative sampling of DCIS, axillary assessment by ultrasound with needle biopsy for suspected metastases, risk stratification for sentinel node biopsy (for high grade or extensive DCIS) and avoiding axillary clearance for a pre-operative diagnosis of DCIS alone should reduce unnecessary axillary surgery. Standards using such criteria for axillary surgery in screen-detected DCIS should be integrated into the NHS BSP. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Helical tomotherapy in patients with breast cancer and complex treatment volumes.

PubMed

Cendales, Ricardo; Schiappacasse, Luis; Schnitman, Franco; García, Graciela; Marsiglia, Hugo

2011-04-01

To describe early clinical results of tomotherapy treatment in patients with breast cancer and complex treatment volumes. Ten patients were treated with tomotherapy between January 2009 and March 2010. Treatment planning objectives were to cover at least 95% of the planning target volume with the 95% isodose; to have a minimum dose of 90% and a maximum dose of 105%. All treatments included daily CT/megavoltage image guidance. Acute toxicity was recorded weekly. Six patients were treated because constraints were not accomplished for heart, lung or contralateral breast in a previous three-dimensional conformal plan; two for preexisting cardiac or pulmonary disease, and two more for bilateral breast irradiation. Treatment volumes included the whole breast in the majority of patients, as well as the supraclavicular and the internal mammary chain nodes when indicated. Most patients were older than 50 years, and had an early breast cancer, with positive oestrogen receptors, negative HER2 expression and a poorly differentiated, infiltrating ductal carcinoma. The majority of patients had received neoadjuvant chemotherapy associated to breast-conserving surgery and adjuvant hormonotherapy. Median homogeneity index was 1.09; median coverage index was 0.81. Median V20Gy and V10Gy for ipsilateral lung was 20% and 37.1% respectively. Median V25 and V35 for heart was 15% and 4% respectively. Median dose for contralateral breast was 7 Gy. Skin acute toxicity was grade 1 in 41.7% and grade 2 in 58.3%. Tomotherapy is a technique capable of delivering a well tolerated treatment with high homogeneity and coverage indexes and high capabilities for sparing the organs at risk in patients with anatomically complex breast cancer, bilateral breast cancer, indication for internal mammary chain node irradiation, cardiac toxicity derived from chemotherapy, or preexisting cardiac or pulmonary disease. Further studies are required to evaluate local control and late toxicity.

[Sentinel node biopsy in patients with multifocal and multicentric breast cancer: A 5-year follow-up].

PubMed

Blanco Saiz, I; López Carballo, M T; Martínez Fernández, J; Carrión Maldonado, J; Cabrera Pereira, A; Moral Alvarez, S; Santamaría Girón, L; Cantero Cerquella, F; López Secades, A; Díaz González, D; Llaneza Folgueras, A; Aira Delgado, F J

2014-01-01

Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up. A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32-126 months). Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group. SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Transaxillary breast augmentation: two breast cancer patients with successful sentinel lymph node diagnosis.

PubMed

Mottura, A Aldo; Del Castillo, René

2007-01-01

In recent years, some surgeons have been warned of possible problems with sentinel lymph node diagnosis (SLND) for patients who have undergone transaxillary breast augmentation (TBA), although no scientific studies support this warning. The authors report two additional cases of breast cancer in which the SLND was successfully performed for patients with previous TBA. The surgical anatomy of the axilla, the groups of lymph nodes, and a personal way of performing TBA are described. Five other reports concerning the same issue are thoroughly discussed. Four of these are clinical in vivo reports, and one is a cadaver study. The four in vivo studies and what we are reporting now clearly demonstrate that what was said regarding possible problems in the SLND after TBA was not founded on clinical research and contradicts these five clinical findings.

Surgeon specialization and use of sentinel lymph node biopsy for breast cancer

PubMed Central

Yen, Tina W.F.; Laud, Purushuttom W.; Sparapani, Rodney A.; Nattinger, Ann B.

2014-01-01

IMPORTANCE Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative breast cancer patients. It is not known whether SLNB rates differ by surgeon expertise. If surgeons with less breast cancer expertise are less likely to offer SLNB to clinically node-negative patients, this practice pattern could lead to unnecessary axillary lymph node dissections (ALND) and lymphedema. OBJECTIVE To explore potential measures of surgical expertise (including a novel objective specialization measure – percentage of a surgeon’s operations devoted to breast cancer determined from claims) on the use of SLNB for invasive breast cancer. DESIGN Population-based prospective cohort study. Patient, tumor, treatment and surgeon characteristics were examined. SETTING California, Florida, Illinois PARTICIPANTS Elderly (65+ years) women identified from Medicare claims as having had incident invasive breast cancer surgery in 2003. MAIN OUTCOME MEASURES Type of axillary surgery performed. RESULTS Of the 1,703 women treated by 863 different surgeons, 56% underwent an initial SLNB, 37% initial ALND and 6% no axillary surgery. The median annual surgeon Medicare volume of breast cancer cases was 6 (range: 1.5–57); the median surgeon percentage of breast cancer cases was 4.6% (range: 0.7%–100%). After multivariable adjustment of patient and surgeon factors, women operated on by surgeons with higher volumes and percentages of breast cancer cases had a higher likelihood of undergoing SLNB. Specifically, women were most likely to undergo SLNB if operated on by high volume surgeons (regardless of percentage) or by lower volume surgeons with a high percentage of cases devoted to breast cancer. In addition, membership in the American Society of Breast Surgeons (OR 1.98, CI 1.51–2.60) and Society of Surgical Oncology (OR 1.59, CI 1.09–2.30) were independent predictors of women undergoing an initial SLNB. CONCLUSIONS AND RELEVANCE Patients treated by surgeons with more experience and focus in breast cancer were significantly more likely to undergo SLNB, highlighting the importance of receiving initial treatment by specialized providers. Factors relating to specialization in a particular area, including our novel surgeon percentage measure, require further investigation as potential indicators of quality of care. PMID:24369337

Intraoperative assessment of sentinel lymph node by one-step nucleic acid amplification in breast cancer patients after neoadjuvant treatment reduces the need for a second surgery for axillary lymph node dissection.

PubMed

Espinosa-Bravo, Martin; Navarro-Cecilia, Joaquin; Ramos Boyero, Manuel; Diaz-Botero, Sebastian; Dueñas Rodríguez, Basilio; Luque López, Carolina; Ramos Grande, Teresa; Ruano Perez, Ricardo; Peg, Vicente; Rubio, Isabel T

2017-02-01

Sentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). Intraoperative assessment of SLN by frozen sections can produce false negative results. The aim of this study was to compare two different techniques of intraoperative assessment of SLN in breast cancer patients treated with NAC: frozen section (FS) and molecular assay (OSNA). A multicenter cohort of 320 consecutive breast cancer patients treated with NAC between 2010 and 2014 was analyzed. FS was performed intraoperatively in 166 patients (H&E cohort) and OSNA in 154 patients (OSNA cohort). A mean of 2.15 SLNs by FS and 1.22 SLNs by OSNA was assessed (p = 0.03). SLN metastasis was found in 44 patients (26.5%) by FS and in 48 (31.2%) by OSNA (p = 0.4). There was no statistical significance in rates of macrometastasis (75%), micrometastasis (20.5%) or ITCs (4.5%) when assessed by FS compared to OSNA (52.3%, 36.3% and 11.4%, respectively) (p = 0.06). There were 10 patients in the H&E cohort with positive-SLN in the definitive pathology assessment with negative intraoperative FS. When OSNA and definitive pathology were compared, there were no differences in rates of macrometastasis (61.1%), micrometastasis (33.3%) nor ITCs (5.6%) (p = 0.5). Fifty-four patients in the H&E cohort and 44 in the OSNA cohort had ALND after positive-SLNs. ALND was performed in a second surgery in 10 patients (18.5%) in the H&E cohort for intraoperative FS false negative results, 90% being micrometastasis. 42 out of 44 patients (95.5%) in the OSNA cohort had an ALND in the same surgery (p = 0.03). OSNA assay detects SLNs metastases as accurately as conventional pathology in the NAC setting. Intraoperative definitive assessment of the SLN by OSNA reduces the need for a second surgery for ALND in 18.5% of breast cancer patients with a positive-SLN after NAC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prolactin receptor expression in gynaecomastia and male breast carcinoma.

PubMed

Ferreira, M; Mesquita, M; Quaresma, M; André, S

2008-07-01

Despite the well-established function of prolactin (PRL) in normal breast development, its role in breast cancer pathogenesis is still controversial. PRL activity is dependent on the activation of a transmembrane protein, the PRL receptor (PRLR). The aim was to evaluate and compare PRLR expression in gynaecomastia and male breast carcinoma (MBC). PRLR expression was detected immunohistochemically in 30 cases of gynaecomastia and 30 cases of MBC. The whole series was also assessed for oestrogen receptors (ER), progesterone receptors (PR) and androgen receptors (AR). A cut-off of 10% was used as the criterion for positivity. Histological type and tumour differentiation were evaluated. Pathological stage was assessed [Tumour Node Metastasis (TNM)-International Union Against Cancer system]. Statistical analysis was performed with Fisher's exact test. PRLR positivity was seen in 20% of gynaecomastia cases and in 60% of MBC cases (P = 0.003). In gynaecomastia immunoreactivity was predominantly observed in luminal cell borders, whereas in MBC the reactivity was heterogeneous and mainly cytoplasmic. There was no statistically significant correlation between PRLR expression and ER, PR, AR, pTNM, or histological grade. PRLR is significantly more expressed in MBC than in gynaecomastia, and with different patterns of reactivity, suggesting a role for PRL in male breast carcinogenesis.

Synchronous Bilateral Male Breast Cancer: A Case Report

PubMed Central

Sun, Woo-Young; Lee, Ki-Hyeong; Lee, Ho-Chang; Ryu, Dong-Hee; Park, Jin-Woo; Yun, Hyo-Young

2012-01-01

Synchronous bilateral breast cancer is extremely rare in men and has not, up to date, been reported in Korea. A 54-year-old man presented with a palpable mass in the right breast. The right nipple was retracted and bilateral axillary accessory breasts and nipples were present. On physical examination, a 2 cm-sized mass was palpated directly under the right nipple, and, with squeezing, bloody discharge developed in a single duct of the left nipple. There was no palpable mass in the left breast, and axillary lymph nodes were not palpable. Physical examination of external genitalia revealed a unilateral undescended testis on the left side. Synchronous bilateral breast cancer was diagnosed using mammography, ultrasonography, and core-needle biopsy. Histopathological examination revealed invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast. Bilateral total mastectomy, sentinel lymph node biopsy, and excision of accessory breasts in the axilla were performed. PMID:22807945

Synchronous bilateral male breast cancer: a case report.

PubMed

Sun, Woo-Young; Lee, Ki-Hyeong; Lee, Ho-Chang; Ryu, Dong-Hee; Park, Jin-Woo; Yun, Hyo-Young; Song, Young-Jin

2012-06-01

Synchronous bilateral breast cancer is extremely rare in men and has not, up to date, been reported in Korea. A 54-year-old man presented with a palpable mass in the right breast. The right nipple was retracted and bilateral axillary accessory breasts and nipples were present. On physical examination, a 2 cm-sized mass was palpated directly under the right nipple, and, with squeezing, bloody discharge developed in a single duct of the left nipple. There was no palpable mass in the left breast, and axillary lymph nodes were not palpable. Physical examination of external genitalia revealed a unilateral undescended testis on the left side. Synchronous bilateral breast cancer was diagnosed using mammography, ultrasonography, and core-needle biopsy. Histopathological examination revealed invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast. Bilateral total mastectomy, sentinel lymph node biopsy, and excision of accessory breasts in the axilla were performed.

Metastasis of ovarian cancer to the breast: A report of two cases and a review of the literature

PubMed Central

TEMPFER, CLEMENS B.; EL FIZAZI, NARIMAN; ERGONENC, HASSAN; SOLASS, WIEBKE

2016-01-01

Metastasis of ovarian cancer to the breast (MOCB) is a rare event. Clinical presentations of MOCB vary and surgery is the mainstay of treatment. The current study presents two cases of MOCB in women with recurrent ovarian cancer first diagnosed in April 2011 and October 2013, respectively. The patients presented to the clinic with a localized, palpable, painful mass in the upper outer quadrant of the right breast and a centrally localized, palpable, painful mass of the left breast, respectively. Breast sonography and mammography showed a singular, round, homogenous tumor with irregular borders in each case. An ipsilateral enlarged axillary node was palpable in one case. Tumor biopsy revealed an undifferentiated adenocarcinoma of unknown origin in one case and a moderately-differentiated adenocarcinoma suspected to be breast cancer in the other case. Tumor cells were positive for estrogen receptor and paired box 8, and negative for GATA binding protein 3 in the two cases. Palliative mastectomy was performed in one case and lumpectomy with ipsilateral axillary sentinel node biopsy in the other case, and the final histology revealed MOCB in each. The post-operative course of the disease was uneventful and the patients continued with their ovarian cancer-specific chemotherapy. One patient succumbed to disease progression 2 months after breast surgery. The other patient remains alive and is currently undergoing systemic chemotherapy. The current study also presents a review of 110 cases of MOCB identified in a literature search of Pubmed. Data from these studies, including the clinical and histological characteristics of MOCB, and the clinical management and prognosis are discussed. Overall, MOCB is rare, with distinct clinical and histological features. The disease is usually treated with local surgical excision or mastectomy and has a poor prognosis. PMID:27313731

Variations in locoregional therapy in postmenopausal patients with early breast cancer treated in different countries.

PubMed

van Nes, J G H; Seynaeve, C; Jones, S; Markopoulos, C; Putter, H; van de Velde, C J H; Hasenburg, A; Rea, D W; Vannetzel, J-M; Dirix, L; Hozumi, Y; Kerin, M J; Kieback, D G; Meershoek-Klein Kranenbarg, W M; Hille, E T M; Nortier, J W R

2010-05-01

The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial is an international randomized trial evaluating the efficacy and safety of exemestane, alone or following tamoxifen. The large number of patients already recruited offered the opportunity to explore locoregional treatment practices between countries. Patients were enrolled in Belgium, France, Germany, Greece, Ireland, Japan, the Netherlands, the UK and the USA. The core protocol had minor differences in eligibility criteria between countries, reflecting variations in national guidelines and practice regarding adjuvant endocrine therapy. Between 2001 and 2006, 9779 patients of mean(s.d.) age 64(9) years were randomized. Some 58.4 per cent had T1 tumours (range between countries 36.8-75.9 per cent; P < 0.001) and 47.3 per cent were axillary node positive (range 25.9-84.6 per cent; P < 0.001). Independent factors for type of breast surgery were country, age, tumour status and calendar year of surgery. After breast-conserving surgery, radiotherapy was given to 93.2 per cent of patients, 86.0 per cent in the USA and 100 per cent in France. Axillary lymph node dissection was performed in 82.0 (range 74.6-99.1) per cent. Despite international consensus guidelines, wide global variations were observed in treatment practices of early breast cancer. There should be further efforts to optimize locoregional treatment for breast cancer worldwide. Copyright 2010 British Journal of Surgery Society Ltd.

[Is radiotherapy of the lymph node stages useful after the conservative treatment of the initial stage of breast carcinoma?].

PubMed

Gava, A; Coghetto, F

1989-05-01

Twenty-four lectures were reviewed of the XXXIII SIRMN National Congress (Rome, October 1988) on the conservative radiosurgical treatment of breast cancer. A whole of 3462 cases were divided into 2 groups: group A--2824 patients who underwent targeted radiotherapy after conservative surgery (mostly quadrantectomy)--and group B--638 patients where, in case of N+ and internal quadrant tumors, irradiation was extended to lymph nodes. No significant differences were demonstrated between group A and group B as far as loco-regional relapses were concerned. Thus, no significant advantage seems to be yielded by lymph node irradiation in the early treatment of breast cancer.

Impact of sentinel lymph node biopsy on immediate breast reconstruction after mastectomy.

PubMed

Wood, Benjamin C; David, Lisa R; Defranzo, Anthony J; Stewart, John H; Shen, Perry; Geisinger, Kim R; Marks, Malcolm W; Levine, Edward A

2009-07-01

Traditionally, sentinel lymph node biopsy (SLNB) is performed at the time of mastectomy and reconstruction. However, several groups have advocated SLNB as a separate outpatient procedure before mastectomy, when immediate reconstruction is planned, to allow for complete pathologic evaluation. The purpose of this study was to determine the impact of intraoperative analysis of SLNB on the reconstructive plan when performed at the same time as definitive surgery. A retrospective review was conducted of all mastectomy cases performed at a single institution between September 1998 and November 2007. Of the 747 mastectomy cases reviewed, SLNB was conducted in 344 cases, and there was immediate breast reconstruction in 193 of those cases. There were 27 (7.8%) false negative and three (0.9%) false positive intraoperative analysis of SLNB. Touch preparation analysis from the SLNB changed the reconstructive plan in four (2.1%) cases. In our experience, SLNB can be performed at the time of mastectomy with minimal impact on the reconstructive plan. A staged approach incurs significant additional expense, increases the delay in initiation of systemic therapy and the propensity of procedure-related morbidity; therefore, SLNB should not be performed as a separate procedure before definitive surgery with immediate breast reconstruction.

Quantification of Estrogen Receptor Expression in Normal Breast Tissue in Postmenopausal Women With Breast Cancer and Association With Tumor Subtypes.

PubMed

Gulbahce, H Evin; Blair, Cindy K; Sweeney, Carol; Salama, Mohamed E

2017-09-01

Estrogen exposure is important in the pathogenesis of breast cancer and is a contributing risk factor. In this study we quantified estrogen receptor (ER) alpha expression in normal breast epithelium (NBR) in women with breast cancer and correlated it with breast cancer subtypes. Tissue microarrays were constructed from 204 breast cancer patients for whom normal breast tissue away from tumor was available. Slides stained with ER were scanned and expression in normal terminal duct lobular epithelium was quantitated using computer-assisted image analysis. ER expression in normal terminal duct lobular epithelium of postmenopausal women with breast cancer was significantly associated with estrogen and triple (estrogen, progesterone receptors, and HER2) negative phenotypes. Also increased age at diagnosis was significantly associated with ER expression in NBR. ER positivity in normal epithelium did not vary by tumor size, lymph node status, tumor grade, or stage. On the basis of quantitative image analysis, we confirm that ER expression in NBR increases with age in women with breast cancer, and report for the first time, a significant association between ER expression in NBR with ER-negative and triple-negative cancers in postmenopausal women.

Phenotypic analysis of familial breast cancer: comparison of BRCAx tumors with BRCA1-, BRCA2-carriers and non-familial breast cancer.

PubMed

Aloraifi, F; Alshehhi, M; McDevitt, T; Cody, N; Meany, M; O'Doherty, A; Quinn, C M; Green, A J; Bracken, A; Geraghty, J G

2015-05-01

Women with inherited pathogenic mutations in the BRCA1 or BRCA2 genes have up to an 85% risk of developing breast cancer in their lifetime. However, only about 20% of familial breast cancer is attributed to mutations in BRCA1 and BRCA2, while a further 5-10% are attributed to mutations in other rare susceptibility genes such as TP53, STK11, PTEN, ATM and CHEK2. Despite extensive efforts to explain the missing heritability of this disease, the majority of familial clustering in breast cancer remains largely unexplained. We aim to analyze the pathology of familial cases of which no pathogenic mutation is yet identified. We compared the pathological phenotype of BRCA1/BRCA2 negative familial breast cancer (BRCAx) to BRCA1-positive, BRCA2-positive and sporadic cases without a family history. Age-adjusted analysis is summarized in odd's ratios and confidence intervals for tumor type, grade, lymph node, ER and HER2 status. We found non-familial cases to be more likely to be ER positive (P = 0.041) as compared with BRCAx tumors. More cases of lobular carcinoma were found with BRCAx as compared to BRCA1 tumors (P = 0.05). After multivariate logistic regression analysis, BRCAx tumors are more likely ER positive (P = 0.001) and HER2 positive (P = 0.047) in comparison to BRCA1. Conversely, BRCAx cases are less likely to be ER positive (P = 0.02) but more likely to be HER2 positive (P = 0.021) as compared with BRCA2 tumors. Our findings suggest that BRCA1, BRCA2 and BRCAx tumors differ in phenotype from non-familial and familial BRCA1-positive and BRCA2-positive tumors. Further studies will need to be performed in this important population in order to develop strategies for early detection and prevention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Technical limits of comparison of step-sectioning,immunohistochemistry and RT-PCR on breast cancer sentinel nodes: a study on methacarn-fixed tissue.

PubMed

Daniele, Lorenzo; Annaratone, Laura; Allia, Elena; Mariani, Sara; Armando, Enrico; Bosco, Martino; Macrì, Luigia; Cassoni, Paola; D'Armento, Giuseppe; Bussolati, Gianni; Cserni, Gabor; Sapino, Anna

2009-09-01

The optimal pathological assessment of sentinel nodes (SLNs) in breast cancer is a matter of debate. Currently, multilevel histological evaluation and immunohistochemistry (IHC) are recommended, but alternative RT-PCR procedures have been developed. To assess the reliability of these different procedures, we devised a step-sectioning protocol at 100 micron-intervals of 74 SLNs using methacarn fixation. mRNA was extracted from sections collected from levels 4 to 5. Mammaglobin, CEA and CK19 were used for RT-PCR. mRNA extraction was successful in 69 SLNs. Of these, 7 showed macrometastases (>2mm), 2 showed micrometastases (<2 mm) and 7 showed isolated tumour cells (ITC) by IHC. RT-PCR was positive for the three markers in 6 of 7 macrometastases and in 1 of 2 micrometastases. In the 2 RT-PCR negative cases, metastases were detected only on sections distant from those analysed by RT-PCR. CEA and/or CK19 were positive by RT-PCR in 3 of 7 ITC and in 23 morphologically negative SLNs. In conclusion, the main goal of our study was to show that the use of alternate sections of the same sample for different procedures is the key reason for the discrepancies between molecular and morphological analyses of SLN. We believe that only prospective studies with quantitative mRNA analysis of specific metastatic markers on the whole lymph node can elucidate the utility of molecular assessments of SLN.

Detection of pAkt protein in imprint cytology of invasive breast cancer: Correlation with HER2/neu, hormone receptors, and other clinicopathological variables.

PubMed

Vasou, Olympia; Skagias, Lazaros; Anastasia, Margariti; Paulina, Athanasiadou; Patsouris, Efstratios; Politi, Ekaterini

2015-01-01

Akt is a serine/threonine protein kinase and has emerged as a crucial regulator of widely divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Activation of Akt/protein kinase B has been positively associated with human epidermal growth-factor receptor 2 (HER2)/neu overexpression in breast carcinoma and a worse outcome among endocrine treated patients. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Archival tumor tissues from 100 patients with invasive breast carcinoma were analyzed by immunocytochemistry. This study describes the results of immunocytochemical pAkt expression in breast carcinoma imprints, prepared from cut surfaces of freshly removed tumors. Both nuclear and cytoplasmic expressions were evaluated for pAkt. Nuclear and cytoplasmic positive scores of 72% (72/100) and 42% (42/100), respectively, were found. Coexistence of nuclear and cytoplasmic staining was observed in 32 cases (32/100). Nuclear positive staining correlated with HER2/neu overexpression (P = 0.043) and was significantly associated with positive involvement of axillary lymph nodes (P = 0.013). No correlation was found between cytoplasmic pAkt rate and clinicopathological parameters, estrogen receptor, progesterone receptor or HER2/neu expression. pAkt expression can be evaluated in cytological material and may add valuable information to current prognostic models for breast cancer. pAkt overexpression appears to be linked with potentially aggressive tumor phenotype in invasive breast carcinoma.

Armc8 expression was elevated during atypia-to-carcinoma progression and associated with cancer development of breast carcinoma.

PubMed

Fan, Chuifeng; Zhao, Yang; Mao, Xiaoyun; Miao, Yuan; Lin, Xuyong; Jiang, Guiyang; Zhang, Xiupeng; Han, Qiang; Luan, Lan; Wang, Enhua

2014-11-01

Armadillo repeat-containing protein 8 (Armc8) is a key factor to regulate cell membrane adhesion complex through promoting α-catenin degradation. However, its expression and function in human malignant tumors are largely unknown. Here, we present our study investigating Armc8 expression in tumor and non-tumor breast tissues including 45 normal epithelia, 53 lesions of hyperplasia with or without dysplasia, 22 benign tumors, and 92 carcinomas including 28 carcinomas in situ and 64 infiltrating carcinomas using immunohistochemistry (IHC) and Western blotting study. Armc8 expression was detected mainly in the cytoplasm with occasional membrane immunostaining. The positive rate of Armc8 expression in normal breast epithelia (8.9%, four out of 45) was very low. No significant difference was found between Armc8 expression in usual ductal hyperplasia (UDH) (11.1%, two out of 18), benign breast tumors including intraductal papilloma (10.0%, one out of 10) and fibroadenoma (8.3%, one out of 12), and normal breast epithelia (p>0.05). Elevated expression of Armc8 was found in breast epithelia with dysplasia (24.0%, six out of 25) compared to that in normal breast epithelia, UDH, and benign breast tumors (p<0.05). Armc8 expression in breast carcinoma including breast carcinoma in situ (10/28, 35.7%), infiltrating ductal carcinoma (60.7%, 34/56), and infiltrating lobular carcinoma (50.0%, 4/8) was higher than that in normal breast epithelia, UDH, benign breast tumors, and breast epithelia with dysplasia (p<0.05). The highest expression of Armc8 was found in infiltrating breast carcinoma (59.4%, 38/64) compared to all the other breast tissues. Higher Armc8 expression was found to be linked to lymph node metastasis and advanced tumor-node-metastasis (TNM) stages (III+IV) in infiltrating breast carcinoma (p<0.05). We further confirmed Armc8 expression in breast epithelial cell line MCF10A and breast carcinoma cell lines including MCF-7, MDA-MB-231, and ZR751 using Western blotting and immunofluorescent study. These results indicate that the elevated expression of Armc8 may be involved in carcinogenesis including atypia-to-carcinoma progression and cancer development of breast carcinoma.

Adoption of Gene Expression Profile Testing and Association With Use of Chemotherapy Among Women With Breast Cancer

PubMed Central

Hassett, Michael J.; Silver, Samuel M.; Hughes, Melissa E.; Blayney, Douglas W.; Edge, Stephen B.; Herman, James G.; Hudis, Clifford A.; Marcom, P. Kelly; Pettinga, Jane E.; Share, David; Theriault, Richard; Wong, Yu-Ning; Vandergrift, Jonathan L.; Niland, Joyce C.; Weeks, Jane C.

2012-01-01

Purpose Gene expression profile (GEP) testing is a relatively new technology that offers the potential of personalized medicine to patients, yet little is known about its adoption into routine practice. One of the first commercially available GEP tests, a 21-gene profile, was developed to estimate the benefit of adjuvant chemotherapy for hormone receptor–positive breast cancer (HR-positive BC). Patients and Methods By using a prospective registry data set outlining the routine care provided to women diagnosed from 2006 to 2008 with HR-positive BC at 17 comprehensive and community-based cancer centers, we assessed GEP test adoption and the association between testing and chemotherapy use. Results Of 7,375 women, 20.4% had GEP testing and 50.2% received chemotherapy. Over time, testing increased (14.7% in 2006 to 27.5% in 2008; P < .01) and use of chemotherapy decreased (53.9% in 2006 to 47.0% in 2008; P < .01). Characteristics independently associated with lower odds of testing included African American versus white race (odds ratio [OR], 0.70; 95% CI, 0.54 to 0.92) and high school or less versus more than high school education (OR, 0.63; 95% CI, 0.52 to 0.76). Overall, testing was associated with lower odds of chemotherapy use (OR, 0.70; 95% CI, 0.62 to 0.80). Stratified analyses demonstrated that for small, node-negative cancers, testing was associated with higher odds of chemotherapy use (OR, 11.13; 95% CI, 5.39 to 22.99), whereas for node-positive and large node-negative cancers, testing was associated with lower odds of chemotherapy use (OR, 0.11; 95% CI, 0.07 to 0.17). Conclusion There has been a progressive increase in use of this GEP test and an associated shift in the characteristics of and overall reduction in the proportion of women with HR-positive BC receiving adjuvant chemotherapy. PMID:22585699

Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015

PubMed Central

Coates, A. S.; Winer, E. P.; Goldhirsch, A.; Gelber, R. D.; Gnant, M.; Piccart-Gebhart, M.; Thürlimann, B.; Senn, H.-J.

2015-01-01

The 14th St Gallen International Breast Cancer Conference (2015) reviewed substantial new evidence on locoregional and systemic therapies for early breast cancer. Further experience has supported the adequacy of tumor margins defined as ‘no ink on invasive tumor or DCIS’ and the safety of omitting axillary dissection in specific cohorts. Radiotherapy trials support irradiation of regional nodes in node-positive disease. Considering subdivisions within luminal disease, the Panel was more concerned with indications for the use of specific therapies, rather than surrogate identification of intrinsic subtypes as measured by multiparameter molecular tests. For the treatment of HER2-positive disease in patients with node-negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For premenopausal patients with endocrine responsive disease, the Panel endorsed the role of ovarian function suppression with either tamoxifen or exemestane for patients at higher risk. The Panel noted the value of an LHRH agonist given during chemotherapy for premenopausal women with ER-negative disease in protecting against premature ovarian failure and preserving fertility. The Panel noted increasing evidence for the prognostic value of commonly used multiparameter molecular markers, some of which also carried prognostic information for late relapse. The Panel noted that the results of such tests, where available, were frequently used to assist decisions about the inclusion of cytotoxic chemotherapy in the treatment of patients with luminal disease, but noted that threshold values had not been established for this purpose for any of these tests. Multiparameter molecular assays are expensive and therefore unavailable in much of the world. The majority of new breast cancer cases and breast cancer deaths now occur in less developed regions of the world. In these areas, less expensive pathology tests may provide valuable information. The Panel recommendations on treatment are not intended to apply to all patients, but rather to establish norms appropriate for the majority. Again, economic considerations may require that less expensive and only marginally less effective therapies may be necessary in less resourced areas. Panel recommendations do not imply unanimous agreement among Panel members. Indeed, very few of the 200 questions received 100% agreement from the Panel. In the text below, wording is intended to convey the strength of Panel support for each recommendation, while details of Panel voting on each question are available in supplementary Appendix S2, available at Annals of Oncology online. PMID:25939896

Effect of {sup 18}F-FDG PET/CT Imaging in Patients With Clinical Stage II and III Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groheux, David; Moretti, Jean-Luc; EAD Imagerie Moleculaire Diagnostique et Ciblage Therapeutique, IUH, University of Paris VII, Paris

2008-07-01

Purpose: To investigate the potential effect of using {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. Methods and Materials: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. Results: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in themore » subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. Conclusions: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.« less

Risk of Recurrence or Contralateral Breast Cancer More than 5 Years After Diagnosis of Hormone Receptor-Positive Early-Stage Breast Cancer.

PubMed

Wilson, Sheridan; Speers, Caroline; Tyldesley, Scott; Chia, Stephen; Kennecke, Hagen; Ellard, Susan; Lohrisch, Caroline

2016-08-01

Three large studies have shown a survival benefit from 10 years of adjuvant hormone therapy (AHT). We evaluated the risk of an event 5 years after the initial breast cancer (BC) diagnosis and identified the prognostic factors to assist clinicians considering extended AHT. Patients newly referred to the BC Cancer Agency with stage I to III estrogen receptor-positive BC diagnosed from 1989 to 2004 who had undergone AHT were identified by the BC Cancer Agency's Breast Cancer Outcomes Unit. Cases with recurrence, death, or contralateral BC occurring within the first 5 years were excluded. The 10-year event-free survival (EFS) and 95% confidence intervals (CIs) were calculated using the Kaplan-Meier method. This provided estimates of recurrence risk after the fifth year following the diagnosis. The histopathologic and age variables were examined for prognostic value by univariate analysis. Within our cohort, 6615 women were postmenopausal and 1886 were premenopausal at the BC diagnosis. The median follow-up period was 11 years. The 10-year EFS for women aged < 50 years with stage I, II, and III disease was 94.8% (95% CI, 92.8%-96.3%), 88.3% (95% CI, 86.0%-90.2%), and 80.4% (95% CI, 73.6%-85.6%), respectively. Among women aged ≥ 50 years, the corresponding EFS rates were 94.8% (95% CI, 93.8%-95.6%), 86.3% (95% CI, 85.0%-87.5%), and 73.8% (95% CI, 69.1%-77.8%). EFS varied significantly by grade. The 10-year recurrence risk was < 10% with stage I cancer (any grade) and for stage II (node-negative and node-positive), grade I cancer. Our data have identified BCs associated with a very low recurrence risk 5 to 10 years after diagnosis, providing women with such cancers confidence about a decision to discontinue AHT after 5 years. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of the Prognostic and Predictive Utilities of the 21-Gene Recurrence Score Assay and Adjuvant! for Women with Node-Negative, ER-Positive Breast Cancer: Results from NSABP B-14 and NSABP B-20

PubMed Central

Tang, Gong; Shak, Steven; Paik, Soonmyung; Anderson, Stewart J.; Costantino, Joseph P.; Geyer, Charles E.; Mamounas, Eleftherios P.; Wickerham, D. Lawrence; Wolmark, Norman

2012-01-01

The Oncotype DX® Recurrence Score® (RS) is a validated genomic predictor of outcome and response to adjuvant chemotherapy in ER-positive breast cancer. Adjuvant! was developed using SEER registry data and results from the Early Breast Cancer Clinical Trialists’ overview analyses to estimate outcome and benefit from adjuvant hormonal therapy and chemotherapy. In this report we compare the prognostic and predictive utility of these two tools in node-negative, ER-positive breast cancer. RS and Adjuvant! results were available from 668 tamoxifen-treated NSABP B-14 patients: 227 tamoxifen-treated NSABP B-20 patients, and 424 chemotherapy-plus-tamoxifen-treated B-20 patients. Adjuvant! results were also available from 1952 B-20 patients. The primary endpoint was distant recurrence-free interval (DRFI). Cox proportional hazards models were used to compare the prognostic and predictive utility of RS and Adjuvant!. Both RS (p<0.001) and Adjuvant! (p=0.002) provided strong independent prognostic information in tamoxifen-treated patients. Combining RS and individual clinicopathologic characteristics provided greater prognostic discrimination than combining RS and the composite Adjuvant!. In the B-20 cohort with RS results (n=651), RS was significantly predictive of chemotherapy benefit (interaction p=0.031 for DRFI, p=0.011 for overall survival [OS], p=0.082 for disease-free survival [DFS]), but Adjuvant! was not (interaction p=0.99, p=0.311 and p=0.357, respectively). However, in the larger B-20 sub-cohort (n=1952), Adjuvant! was significantly predictive of chemotherapy benefit for OS (interaction p=0.009) but not for DRFI (p=0.219) or DFS (p=0.099). Prognostic estimates can be optimized by combining RS and clinicopathologic information instead of simply combining RS and Adjuvant!. RS should be used for estimating relative chemotherapy benefit. PMID:21221771

Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20.

PubMed

Tang, Gong; Shak, Steven; Paik, Soonmyung; Anderson, Stewart J; Costantino, Joseph P; Geyer, Charles E; Mamounas, Eleftherios P; Wickerham, D Lawrence; Wolmark, Norman

2011-05-01

The Oncotype DX Recurrence Score (RS) is a validated genomic predictor of outcome and response to adjuvant chemotherapy in ER-positive breast cancer. Adjuvant! was developed using SEER registry data and results from the Early Breast Cancer Clinical Trialists' overview analyses to estimate outcome and benefit from adjuvant hormonal therapy and chemotherapy. In this report we compare the prognostic and predictive utility of these two tools in node-negative, ER-positive breast cancer. RS and Adjuvant! results were available from 668 tamoxifen-treated NSABP B-14 patients, 227 tamoxifen-treated NSABP B-20 patients, and 424 chemotherapy plus tamoxifen-treated B-20 patients. Adjuvant! results were also available from 1952 B-20 patients. The primary endpoint was distant recurrence-free interval (DRFI). Cox proportional hazards models were used to compare the prognostic and predictive utility of RS and Adjuvant!. Both RS (P < 0.001) and Adjuvant! (P = 0.002) provided strong independent prognostic information in tamoxifen-treated patients. Combining RS and individual clinicopathologic characteristics provided greater prognostic discrimination than combining RS and the composite Adjuvant!. In the B-20 cohort with RS results (n = 651), RS was significantly predictive of chemotherapy benefit (interaction P = 0.031 for DRFI, P = 0.011 for overall survival [OS], P = 0.082 for disease-free survival [DFS]), but Adjuvant! was not (interaction P = 0.99, P = 0.311, and P = 0.357, respectively). However, in the larger B-20 sub-cohort (n = 1952), Adjuvant! was significantly predictive of chemotherapy benefit for OS (interaction P = 0.009) but not for DRFI (P = 0.219) or DFS (P = 0.099). Prognostic estimates can be optimized by combining RS and clinicopathologic information instead of simply combining RS and Adjuvant!. RS should be used for estimating relative chemotherapy benefit.

Sentinel lymph node biopsy before mastectomy and immediate breast reconstruction may predict post-mastectomy radiotherapy, reduce delayed complications and improve the choice of reconstruction.

PubMed

Mannu, G S; Navi, A; Morgan, A; Mirza, S M; Down, S K; Farooq, N; Burger, A; Hussien, M I

2012-01-01

Adjuvant post-mastectomy radiotherapy (RT), which is often unpredicted, is known to increase complications following immediate breast reconstruction (IBR). To investigate the role of sentinel lymph node biopsy (SLN) in predicting RT and improving the choice of IBR. All patients who had mastectomy and IBR between January 2004 and January 2007 were reviewed retrospectively. Axillary staging (clearance or SLN) was performed at the same time until October 2005 (Group 1), when the Unit's protocol was updated to perform SLN initially prior to mastectomy and IBR (Group 2). Patients in Group 2 with positive SLN were offered either a delayed reconstruction or a temporary subpectoral immediate tissue expander, while all options were offered if SLN was negative and in Group 1 patients. One hundred and thirty-nine patients were reviewed. 20 patients received unexpected RT in Group 1 (14 tissue expander, 4 Latissimus Dorsi flap with an implant and 2 DIEP flaps) compared to 11 patients in Group 2 who had a temporary tissue expander due to expected RT (P=0.03). Unexpected RT caused delayed complications in 14 patients (70%) compared to no delayed complications in patients who received expected RT in Group 2. SLN biopsy before IBR helps to predict RT and avoids its complications on breast reconstruction. Patients with positive SLN biopsy are best offered a temporary subpectoral tissue expander for IBR. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

How Long Will I Be Blue? Prolonged Skin Staining Following Sentinel Lymph Node Biopsy Using Intradermal Patent Blue Dye

PubMed Central

Gumus, Metehan; Gumus, Hatice; Jones, Sue E; Jones, Peter A; Sever, Ali R; Weeks, Jennifer

2013-01-01

Summary Background Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. Patients and Methods 236 consecutive patients who had undergone breast conserving surgery and SLNB for breast cancer were reviewed prospectively from January 2007 to December 2009. Results Of the 236 patients, 2 had undergone bilateral surgery, and 41 had been examined in consecutive yearly reviews. Blue discoloration remained visible at the injection site after 12, 24, and > 36 months in 36.5, 23.6, and 8.6% of the patients, respectively. Conclusion The use of patent blue for identification of the sentinel lymph node in patients undergoing breast cancer surgery may result in prolonged discoloration of the skin at the injection site. PMID:24415970

Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results

NASA Astrophysics Data System (ADS)

Bigio, Irving J.; Brown, Stephen G.; Briggs, Gavin M.; Kelley, Christine; Lakhani, Sunil; Pickard, David; Ripley, Paul M.; Rose, Ian; Saunders, Christobel

2000-04-01

We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, medicated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the `sentinel' node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years.

Breast sentinel lymph node navigation with three-dimensional computed tomography-lymphography: a 12-year study.

PubMed

Yamamoto, Shigeru; Suga, Kazuyoshi; Maeda, Kazunari; Maeda, Noriko; Yoshimura, Kiyoshi; Oka, Masaaki

2016-05-01

To evaluate the utility of three-dimensional (3D) computed tomography (CT)-lymphography (LG) breast sentinel lymph node navigation in our institute. Between 2002 and 2013, we preoperatively identified sentinel lymph nodes (SLNs) in 576 clinically node-negative breast cancer patients with T1 and T2 breast cancer using 3D CT-LG method. SLN biopsy (SLNB) was performed in 557 of 576 patients using both the images of 3D CT-LG for guidance and the blue dye method. Using 3D CT-LG, SLNs were visualized in 569 (99%) of 576 patients. Of 569 patients, both lymphatic draining ducts and SLNs from the peritumoral and periareolar areas were visualized in 549 (96%) patients. Only SLNs without lymphatic draining ducts were visualized in 20 patients. Drainage lymphatic pathways visualized with 3D CT-LG (549 cases) were classified into four patterns: single route/single SLN (355 cases, 65%), multiple routes/single SLN (59 cases, 11%) single route/multiple SLNs (62 cases, 11%) and multiple routes/multiple SLNs (73 cases, 13%). SLNs were detected in 556 (99.8%) of 557 patients during SLNB. CT-LG is useful for preoperative visualization of SLNs and breast lymphatic draining routes. This preoperative method should contribute greatly to the easy detection of SLNs during SLNB.

[Local recurrence based on size after conservative surgery in breast cancer stage T1-T2. A population-based study].

PubMed

Martínez-Ramos, David; Fortea-Sanchis, Carlos; Escrig-Sos, Javier; Prats-de Puig, Miguel; Queralt-Martín, Raquel; Salvador-Sanchis, José Luís

2014-01-01

Conservative surgery can be regarded as the standard treatment for most early stage breast tumors. However, a minority of patients treated with conservative surgery will present local or locoregional recurrence. Therefore, it is of interest to evaluate the possible factors associated with this recurrence. A population-based retrospective study using data from the Tumor Registry of Castellón (Valencia, Spain) of patients operated on for primary nonmetastatic breast cancer between January 2000 and December 2008 was designed. Kaplan-Meier curves and log-rank test to estimate 5-year local recurrence were used. Two groups of patients were defined, one with conservative surgery and another with nonconservative surgery. Cox multivariate analysis was conducted. The total number of patients was 410. Average local recurrence was 6.8%. In univariate analysis, only tumor size and lymph node involvement showed significant differences. On multivariate analysis, independent prognostic factors were conservative surgery (hazard ratio [HR] 4.62; 95% confidence interval [CI]: 1.12-16.82), number of positive lymph nodes (HR 1.07; 95% CI: 1.01-1.17) and tumor size (in mm) (HR 1.02; 95% CI: 1.01-1.06). Local recurrence after breast-conserving surgery is higher in tumors >2 cm. Although tumor size should not be a contraindication for conservative surgery, it should be a risk factor to be considered.

Breast self-examination: importance of technique in early diagnosis.

PubMed Central

Hislop, T G; Coldman, A J; Skippen, D H

1984-01-01

Shortly after diagnosis of breast cancer 416 patients were interviewed about their use of screening procedures and the method of tumour detection. Although 72% reported that they performed breast self-examination (BSE), only 12% actually inspected and palpated their breasts monthly. BSE was not significantly associated with tumour size or involvement of the lymph nodes; however, thorough inspection was associated with smaller tumours, and careful palpation with the absence of palpable nodes. Of those who no longer or never had examined their breasts 40% reported having annual breast examinations by their physician and had significantly smaller tumours than did the others. Most of the women (86%) reported having detected their own tumours, and BSE did not significantly increase the likelihood of self-detection. The frequency of use of screening procedures was similar in a sample of women without breast cancer. PMID:6498686

[Breast cancer metastases to the stomach and colon: two case reports].

PubMed

Pulanić, Roland; Jelavić, Marko; Premuzić, Marina; Opacić, Milorad; Jakic-Razumović, Jasminka; Padovan-Stern, Ranka; Vrbanec, Damir

2012-01-01

Summary. Breast cancer has a high potential for metastasis, usually to the lungs, bones, liver and lymph nodes. Metastases in the holow organs of the digestive system are rare and mainly affectes the stomach and colon. They are characterized by very different clinical and radiological manifestations. We have warned that the initial unrecognized breast cancer can appear as a primary tumor of the stomach and colon, and onlya histopathological analysis reveales that it is a metastatic breast cancer. Metastases to the stomach or intestine involve deep layer of the mucosa and pathohistological findings of standard biopsy sample can be falsely negative, despite positive imaging technique (abdominal ultrasound and MSCT, endoscopic ultrasound) that indicate the tumor process. That's,why we emphasize the importance of endoscopic mucosal resection in the detection of malignant process of deeper layers of the gastric mucosa and deep intestinal mucosal biopsies with postoperative analysis of its walls.

Breast Cancer Disparities: A Multicenter Comparison of Tumor Diagnosis, Characteristics, and Surgical Treatment in China and the U.S.

PubMed Central

Sivasubramaniam, Priya G.; Zhang, Bai-Lin; Zhang, Qian; Smith, Jennifer S.; Zhang, Bin; Tang, Zhong-Hua; Chen, Guo-Ji; Xie, Xiao-Ming; Xu, Xiao-Zhou; Yang, Hong-Jian; He, Jian-Jun; Li, Hui; Li, Jia-Yuan; Fan, Jin-Hu

2015-01-01

Background and Objective. Incidence of and mortality rates for breast cancer continue to rise in the People’s Republic of China. The purpose of this study was to analyze differences in characteristics of breast malignancies between China and the U.S. Methods. Data from 384,262 breast cancer patients registered in the U.S. Surveillance, Epidemiology, and End Results (SEER) program from 2000 to 2010 were compared with 4,211 Chinese breast cancer patients registered in a Chinese database from 1999 to 2008. Outcomes included age, race, histology, tumor and node staging, laterality, surgical treatment method, and reconstruction. The Pearson chi-square and Fisher’s exact tests were used to compare rates. Results. Infiltrating ductal carcinoma was the most common type of malignancy in the U.S. and China. The mean number of positive lymph nodes was higher in China (2.59 vs. 1.31, p < .001). Stage at diagnosis was higher in China (stage IIA vs. I, p < .001). Mean size of tumor at diagnosis was higher in China (32.63 vs. 21.57 mm). Mean age at diagnosis was lower in China (48.28 vs. 61.29 years, p < .001). Moreover, 2.0% of U.S. women underwent radical mastectomy compared with 12.5% in China, and 0.02% in China underwent reconstructive surgery. Conclusion. Chinese women were diagnosed at younger ages with higher stage and larger tumors and underwent more aggressive surgical treatment. Prospective trials should be conducted to address screening, surgical, and tumor discrepancies between China and the U.S. Implications for Practice: Breast cancer patients in China are diagnosed at later stages than those in America, which might contribute to different clinical management and lower 5-year survival rate. This phenomenon suggests that an earlier detection and treatment program should be widely implemented in China. By comparing the characteristics of Chinese and Chinese-American patients, we found significant differences in tumor size, lymph nodes metastasis, and age at diagnosis. These consequences indicated that patients with similar genetic backgrounds may have different prognoses due to the influence of environment and social economic determinates. PMID:26240131

Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial.

PubMed

Krag, David N; Anderson, Stewart J; Julian, Thomas B; Brown, Ann M; Harlow, Seth P; Costantino, Joseph P; Ashikaga, Takamaru; Weaver, Donald L; Mamounas, Eleftherios P; Jalovec, Lynne M; Frazier, Thomas G; Noyes, R Dirk; Robidoux, André; Scarth, Hugh Mc; Wolmark, Norman

2010-10-01

Sentinel-lymph-node (SLN) surgery was designed to minimise the side-effects of lymph-node surgery but still offer outcomes equivalent to axillary-lymph-node dissection (ALND). The aims of National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-32 were to establish whether SLN resection in patients with breast cancer achieves the same survival and regional control as ALND, but with fewer side-effects. NSABP B-32 was a randomised controlled phase 3 trial done at 80 centres in Canada and the USA between May 1, 1999, and Feb 29, 2004. Women with invasive breast cancer were randomly assigned to either SLN resection plus ALND (group 1) or to SLN resection alone with ALND only if the SLNs were positive (group 2). Random assignment was done at the NSABP Biostatistical Center (Pittsburgh, PA, USA) with a biased coin minimisation approach in an allocation ratio of 1:1. Stratification variables were age at entry (≤ 49 years, ≥ 50 years), clinical tumour size (≤ 2·0 cm, 2·1-4·0 cm, ≥ 4·1 cm), and surgical plan (lumpectomy, mastectomy). SLN resection was done with a blue dye and radioactive tracer. Outcome analyses were done in patients who were assessed as having pathologically negative sentinel nodes and for whom follow-up data were available. The primary endpoint was overall survival. Analyses were done on an intention-to-treat basis. All deaths, irrespective of cause, were included. The mean time on study for the SLN-negative patients with follow-up information was 95·6 months (range 70·1-126·7). This study is registered with ClinicalTrials.gov, number NCT00003830. 5611 women were randomly assigned to the treatment groups, 3989 had pathologically negative SLN. 309 deaths were reported in the 3986 SLN-negative patients with follow-up information: 140 of 1975 patients in group 1 and 169 of 2011 in group 2. Log-rank comparison of overall survival in groups 1 and 2 yielded an unadjusted hazard ratio (HR) of 1·20 (95% CI 0·96-1·50; p=0·12). 8-year Kaplan-Meier estimates for overall survival were 91·8% (95% CI 90·4-93·3) in group 1 and 90·3% (88·8-91·8) in group 2. Treatment comparisons for disease-free survival yielded an unadjusted HR of 1·05 (95% CI 0·90-1·22; p=0·54). 8-year Kaplan-Meier estimates for disease-free survival were 82·4% (80·5-84·4) in group 1 and 81·5% (79·6-83·4) in group 2. There were eight regional-node recurrences as first events in group 1 and 14 in group 2 (p=0·22). Patients are continuing follow-up for longer-term assessment of survival and regional control. The most common adverse events were allergic reactions, mostly related to the administration of the blue dye. Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes. US Public Health Service, National Cancer Institute, and Department of Health and Human Services. Copyright © 2010 Elsevier Ltd. All rights reserved.

Identification of novel tumor antigens with patient-derived immune-selected antibodies

PubMed Central

Rodriguez-Pinto, Daniel; Sparkowski, Jason; Keough, Martin P.; Phoenix, Kathryn N.; Vumbaca, Frank; Han, David K.; Gundelfinger, Eckart D.; Beesley, Philip

2010-01-01

The identification of tumor antigens capable of eliciting an immune response in vivo may be an effective method to identify therapeutic cancer targets. We have developed a method to identify such antigens using frozen tumor-draining lymph node samples from breast cancer patients. Immune responses in tumor-draining lymph nodes were identified by immunostaining lymph node sections for B-cell markers (CD20&CD23) and Ki67 which revealed cell proliferation in germinal center zones. Antigen-dependent somatic hypermutation (SH) and clonal expansion (CE) were present in heavy chain variable (VH) domain cDNA clones obtained from these germinal centers, but not from Ki67 negative germinal centers. Recombinant VH single-domain antibodies were used to screen tumor proteins and affinity select potential tumor antigens. Neuroplastin (NPTN) was identified as a candidate breast tumor antigen using proteomic identification of affinity selected tumor proteins with a recombinant VH single chain antibody. NPTN was found to be highly expressed in approximately 20% of invasive breast carcinomas and 50% of breast carcinomas with distal metastasis using a breast cancer tissue array. Additionally, NPTN over-expression in a breast cancer cell line resulted in a significant increase in tumor growth and angiogenesis in vivo which was related to increased VEGF production in the transfected cells. These results validate NPTN as a tumor-associated antigen which could promote breast tumor growth and metastasis if aberrantly expressed. These studies also demonstrate that humoral immune responses in tumor-draining lymph nodes can provide antibody reagents useful in identifying tumor antigens with applications for biomarker screening, diagnostics and therapeutic interventions. PMID:18568347

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.

PubMed

Di Filippo, Franco; Di Filippo, Simona; Ferrari, Anna Maria; Antonetti, Raffaele; Battaglia, Alessandro; Becherini, Francesca; Bernet, Laia; Boldorini, Renzo; Bouteille, Catherine; Buglioni, Simonetta; Burelli, Paolo; Cano, Rafael; Canzonieri, Vincenzo; Chiodera, Pierluigi; Cirilli, Alfredo; Coppola, Luigi; Drago, Stefano; Di Tommaso, Luca; Fenaroli, Privato; Franchini, Roberto; Gianatti, Andrea; Giannarelli, Diana; Giardina, Carmela; Godey, Florence; Grassi, Massimo M; Grassi, Giuseppe B; Laws, Siobhan; Massarut, Samuele; Naccarato, Giuseppe; Natalicchio, Maria Iole; Orefice, Sergio; Palmieri, Fabrizio; Perin, Tiziana; Roncella, Manuela; Roncalli, Massimo G; Rulli, Antonio; Sidoni, Angelo; Tinterri, Corrado; Truglia, Maria C; Sperduti, Isabella

2016-12-08

Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (<31%) or recommended (>31%). The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

Earlier detection of breast cancer by surveillance of women at familial risk.

PubMed

Tilanus-Linthorst, M M; Bartels, C C; Obdeijn, A I; Oudkerk, M

2000-03-01

A positive family history increases the risk for breast cancer which oft en occurs at a much younger age than in the general population. We stud ied whether surveillance of these women resulted in the detection of bre ast cancer in an earlier stage than in symptomatic patients with a famil y history. Between January 1994 and April 1998, 294 women with 15-25% r isk (moderate), mean age:43.3 (22-75) years, were screened with a yearly physical examination and mammography from 5 years before the youngest ag e of onset in the family and 384 women with >25% risk (high) for breast cancer, mean age: 42.9 (20-74) years were screened with a physical examination every 6 months and yearly mammography. From September 1995 breast magnetic resonance imaging (MRI) was also carried out for 109 high risk women where mammography showed over 50% density. 26 breast cancers detected under surveillance were significantly more often found in an early T1N0 stage than the 24 breast cancers in patients with a family history referred in that period because of symptoms: 81 versus 46% (P=0.018). Patients under surveillance were also less frequently node-positive than the symptomatic group: 19 versus 42% (P=0.12). 20 patients with a family history referred by our national screening programme in that period had 21 breast cancers detected, 81% in stage T1N0 and 5% node-positive, which was comparable to the results in our national screening programme T1N0 66%, N+ 24% resulting in a 30% reduction in mortality. The incidence in women under surveillance was 10.1 per 1000 in the 'high' risk group and 13.3 per 1000 in the 'moderate' risk group. Expected incidence in an average risk population aged 40-50 years is 1.5, expected if the group consisted of only gene carriers 15 per 1000. 23% of the breast cancers in the surveillance group were detected at physical examination, but occult at mammography. 38% were detected at mammography and clinically occult. Breast MRI (in the subgroup) detected 3 occult breast cancers. The results of this study show that women with a family history benefit from surveillance as breast cancer was detected significantly more often in a favourable T1N0 stage and a mortality reduction comparable to that obtained in our national screening programme may be expected also in women <50 years of age. Both physical examination and mammography contribute to this result, but the former in this study only contributed in women before menopause. Starting surveillance some years before the youngest age of onset in the family may result in higher detection rates. Screening with MRI can detect breast cancers, still occult at physical examination and mammography.

Delineation of Internal Mammary Nodal Target Volumes in Breast Cancer Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jethwa, Krishan R.; Kahila, Mohamed M.; Hunt, Katie N.

Purpose: The optimal clinical target volume for internal mammary (IM) node irradiation is uncertain in an era of increasingly conformal volume-based treatment planning for breast cancer. We mapped the location of gross internal mammary lymph node (IMN) metastases to identify areas at highest risk of harboring occult disease. Methods and Materials: Patients with axial imaging of IMN disease were identified from a breast cancer registry. The IMN location was transferred onto the corresponding anatomic position on representative axial computed tomography images of a patient in the treatment position and compared with consensus group guidelines of IMN target delineation. Results: Themore » IMN location in 67 patients with 130 IMN metastases was mapped. The location was in the first 3 intercostal spaces in 102 of 130 nodal metastases (78%), whereas 18 of 130 IMNs (14%) were located caudal to the third intercostal space and 10 of 130 IMNs (8%) were located cranial to the first intercostal space. Of the 102 nodal metastases within the first 3 intercostal spaces, 54 (53%) were located within the Radiation Therapy Oncology Group consensus volume. Relative to the IM vessels, 19 nodal metastases (19%) were located medially with a mean distance of 2.2 mm (SD, 2.9 mm) whereas 29 (28%) were located laterally with a mean distance of 3.6 mm (SD, 2.5 mm). Ninety percent of lymph nodes within the first 3 intercostal spaces would have been encompassed within a 4-mm medial and lateral expansion on the IM vessels. Conclusions: In women with indications for elective IMN irradiation, a 4-mm medial and lateral expansion on the IM vessels may be appropriate. In women with known IMN involvement, cranial extension to the confluence of the IM vein with the brachiocephalic vein with or without caudal extension to the fourth or fifth interspace may be considered provided that normal tissue constraints are met.« less

Sentinel lymph node biopsy under fluorescent indocyanin green guidance: Initial experience.

PubMed

Aydoğan, Fatih; Arıkan, Akif Enes; Aytaç, Erman; Velidedeoğlu, Mehmet; Yılmaz, Mehmet Halit; Sager, Muhammet Sait; Çelik, Varol; Uras, Cihan

2016-01-01

Sentinel lymph node biopsy can be applied by using either blue dye or radionuclide method or both in breast cancer. Fluorescent imaging with indocyanine green is a new defined method. This study evaluates the applicability of sentinel lymph node biopsy via fluorescent indocyanine green. IC-VIEW (Pulsion Medical Systems AG, Munich, Germany) infrared visualization system was used for imaging. Two mL of indocyanine green was injected to visualize sentinel lymph nodes. After injection, subcutaneous lymphatics were traced and sentinel lymph nodes were found with simultaneous imaging. Sentinel lymph nodes were excised under fluorescent light guidance, and excised lymph nodes were examined histopathologically. Patients with sentinel lymph node metastases underwent axillary dissection. Four patients with sentinel lymph node biopsy due to breast cancer were included in the study. Sentinel lymph nodes were visualized with indocyanine green in all patients. The median number of excised sentinel lymph node was 2 (2-3). Two patients with lymph node metastasis underwent axillary dissection. No metastasis was detected in lymph nodes other than the sentinel nodes in patients with axillary dissection. There was no complication during and after the operation related to the method. According to our limited experience, sentinel lymph node biopsy under fluorescent indocyanine green guidance, which has an advantage of simultaneous visualization, is technically feasible.

Potential use of COX-2–aromatase inhibitor combinations in breast cancer

PubMed Central

Bundred, N J; Barnes, N L P

2005-01-01

Cyclooxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Cyclooxygenase-2-positive tumours tend to be larger, higher grade, node-positive and HER-2/neu-positive. High COX-2 expression is associated with poor prognosis. Cyclooxygenase-2 inhibition reduces the incidence of tumours in animal models, inhibits the development of invasive cancer in colorectal cancer and reduces the frequency of polyps in familial adenomatous polyposis (FAP). These effects may be as a result of increased apoptosis, reduced angiogenesis and/or proliferation. Studies of COX-2 inhibitors in breast cancer are underway both alone and in combination with other agents. There is evidence to suggest that combining COX-2 inhibitors with aromatase inhibitors, growth factor receptor blockers, or chemo- or radiotherapy may be particularly effective. Preliminary results from combination therapy with celecoxib and exemestane in postmenopausal women with advanced breast cancer showed that the combination increased the time to recurrence. Up to 80% of ductal carcinomas in situ (DCISs) express COX-2, therefore COX-2 inhibition may be of particular use in this situation. Cyclooxygenase-2 expression correlates strongly with expression of HER-2/neu. As aromatase inhibitors appear particularly effective in patients with HER-2/neu-positive tumours, the combination of aromatase inhibitors and COX-2 inhibitors may be particularly useful in both DCIS and invasive cancer. PMID:16100520

Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

PubMed Central

Shek, L. L.; Godolphin, W.; Spinelli, J. J.

1987-01-01

The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation. PMID:3435707

False Positive Uptake in Bilateral Gynecomastia on 68Ga-PSMA PET/CT Scan.

PubMed

Sasikumar, Arun; Joy, Ajith; Nair, Bindu P; Pillai, M R A; Madhavan, Jayaprakash

2017-09-01

A 66-year-old man on hormonal therapy with prostate cancer was referred for Ga-PSMA PET/CT scan for biochemical recurrence. Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.

Breast cancer in women aging 35 years old and younger: The Egyptian National Cancer Institute (NCI) experience.

PubMed

Darwish, A D; Helal, A M; Aly El-Din, N H; Solaiman, L L; Amin, A

2017-02-01

The aim is to identify the epidemiological and clinicopathological features associated with young breast cancer (BC) patients and to discuss factors affecting tumor recurrence and DFS. A retrospective analysis was conducted based on medical records from young females patients aged ≤35 years with pathologically confirmed primary breast cancer treated during 2008-2010 at NCI. Cases with non invasive cancer and non carcinoma histology are excluded. Of the 5408 cases diagnosed with breast cancer, 554 were young. Four hundred & fifty eight patients representing 9.2% were within our inclusion criteria. Almost half of the patients (45.9%) presented with stage III. Axillary nodes involvement was in 63.9%, 83.3% were grade 2. More than one quarter of tumors was hormone receptors negative (28.8%) & Her2 was over-expressed in 30%. Mastectomy was offered in 72% while conservative breast surgery in 26%, 69.2% received chemotherapy either adjuvant, neoadjuvant or both, 82.5% received adjuvant radiotherapy, 68.6% received hormonal therapy. Metastatic disease developed in 51.3%, with 31% having more than one site of metastases. After a median follow up period of 66 months, the median DFS of patients was 60 months. The median DFS was significantly shorter among patients with positive lymph nodes (P < 0.0001), ER negative disease (P = 0.045) and stage III disease (P < 0.0001). Breast cancer in young women is aggressive from the time of diagnosis. Our results provide baseline data of young BC in the Middle East & North Africa region; thus, contributing to future epidemiological and hospital-based researches. Copyright © 2016 Elsevier Ltd. All rights reserved.

Up-regulated expression of type II very low density lipoprotein receptor correlates with cancer metastasis and has a potential link to β-catenin in different cancers.

PubMed

He, Lei; Lu, Yanjun; Wang, Peng; Zhang, Jun; Yin, Chuanchang; Qu, Shen

2010-11-03

Very low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cellular signaling. Our group previously reported that enhanced activity of type II VLDLR (VLDLR II), one subtype of VLDLR, promotes adenocarcinoma SGC7901 cells proliferation and migration. The aim of this study is to explore the expression levels of VLDLR II in human gastric, breast and lung cancer tissues, and to investigate its relationship with clinical characteristics and β-catenin expression status. VLDLR II expression was examined using immunohistochemistry (IHC) and Western blot in tumor tissues from 213 gastric, breast and lung cancer patients, tumor adjacent noncancerous tissues by same methods. Correlations between VLDLR II and clinical features, as well as β-catenin expression status were evaluated by statistical analysis. The immunohistochemical staining of VLDLR II showed statistical difference between tumor tissues and tumor adjacent noncancerous tissues in gastric, breast and lung cancers (P = 0.034, 0.018 and 0.043, respectively). Moreover, using Western, we found higher VLDLR II expression levels were associated with lymph node and distant metastasis in gastric and breast cancer (P < 0.05). Furthermore, highly significant positive correlations were found between VLDLR II and β-catenin in gastric cancer (r = 0.689; P < 0.001)breast cancer (r = 0.594; P < 0.001). According to the results of the current study, high VLDLR II expression is correlated with lymph node and distant metastasis in gastric and breast cancer patients, the data suggest that VLDLR II may be a clinical marker in cancers, and has a potential link with β-catenin signaling pathway. This is the first to reveal the closer relationship of VLDLR II with clinical information.

[Selective biopsy of the sentinel lymph node in patients with breast cancer and previous excisional biopsy: is there a change in the reliability of the technique according to time from surgery?].

PubMed

Sabaté-Llobera, A; Notta, P C; Benítez-Segura, A; López-Ojeda, A; Pernas-Simon, S; Boya-Román, M P; Bajén, M T

2015-01-01

To assess the influence of time on the reliability of sentinel lymph node biopsy (SLNB) in breast cancer patients with previous excisional biopsy (EB), analyzing both the sentinel lymph node detection and the lymph node recurrence rate. Thirty-six patients with cT1/T2 N0 breast cancer and previous EB of the lesion underwent a lymphoscintigraphy after subdermal periareolar administration of radiocolloid, the day before SLNB. Patients were classified into two groups, one including 12 patients with up to 29 days elapsed between EB and SLNB (group A), and another with the remaining 24 in which time between both procedures was of 30 days or more (group B). Scintigraphic and surgical detection of the sentinel lymph node, histological status of the sentinel lymph node and of the axillary lymph node dissection, if performed, and lymphatic recurrences during follow-up, were analyzed. Sentinel lymph node visualization at the lymphoscintigraphy and surgical detection were 100% in both groups. Histologically, three patients showed macrometastasis in the sentinel lymph node, one from group A and two from group B. None of the patients, not even those with malignancy of the sentinel lymph node, relapsed after a medium follow-up of 49.5 months (24-75). Time elapsed between EB and SLNB does not influence the reliability of this latter technique as long as a superficial injection of the radiopharmaceutical is performed, proving a very high detection rate of the sentinel lymph node without evidence of lymphatic relapse during follow-up. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

[Ambulatory surgical treatment for breast carcinoma].

PubMed

Barillari, P; Leuzzi, R; Bassiri-Gharb, A; D'Angelo, F; Aurello, P; Naticchioni, E

2001-02-01

The aim of the study is to demonstrate the feasibility and the oncologic effectiveness of quadrantectomy plus sentinel node biopsy performed under local anesthesia, and to demonstrate the economic and psychologic advantages. From October 1996 to March 2000, 71 patients affected with clinical T1 N0 breast cancer, underwent quadrantectomy or tumor resection plus sentinel node biopsy and clinically suspicion axillary nodes biopsy, under local anesthesia at the Casa di Cura "Villa Mafalda" in Rome. Twenty tumors were T1a, 26 T1b e 25 T1c. A mean of 2 sentinel nodes (range 1-4) and a mean of 8 axillary nodes were removed during the procedure. In 2 cases sentinel nodes were not identified. Intraoperative histologic examination showed metastatic sentinel nodes in 11 cases. An axillary node dissection was performed in all cases (>12 nodes) and no other metastatic nodes were found. In all patients clinically suspected nodes were removed. In two cases no evidence of metastasis was found in sentinel nodes, while histologic examination revealed in a patient micrometastasis in one node, and in another patient two metastatic nodes. Fifty-three patients rated the overall surgical, anesthetic and recovery experience as "very satisfactory", 13 "satisfactory" and 5 "unsatisfactory". Patients typically expressed their pleasure at the possibility to return home and stressed the ease of recovery.

Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression.

PubMed

Roth, Carina; Pantel, Klaus; Müller, Volkmar; Rack, Brigitte; Kasimir-Bauer, Sabine; Janni, Wolfgang; Schwarzenbach, Heidi

2011-01-06

As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo®3/7 Assay, respectively. Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008). Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression.

MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis.

PubMed

Yang, Fan; Zhou, Xingchun; Miao, Xia; Zhang, Tao; Hang, Xiaojun; Tie, Ru; Liu, Nan; Tian, Fei; Wang, Fuli; Yuan, Jianlin

2014-05-01

MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.

Harmonic focus versus electrocautery in axillary lymph node dissection for breast cancer: a randomized clinical study.

PubMed

He, Qingqing; Zhuang, Dayong; Zheng, Luming; Fan, Ziyi; Zhou, Peng; Zhu, Jian; Lv, Zhen; Chai, Jixin; Cao, Lei

2012-12-01

Electrocautery has been proven to be associated with prolonged serous drainage that might result in several complications in patients requiring axillary lymph node dissection for breast cancer. We proposed that the Harmonic Focus might outperform electrocautery in axillary lymph node dissection, resulting in shorter operative times and reduced postoperative complications. One hundred twenty-eight women with confirmed T1-3 N1-2 breast cancer were randomly assigned to undergo mastectomy or breast-conserving surgery with axillary dissection by using Harmonic Focus or electrocautery. Sixty-four has surgery with Harmonic Focus (group A) and 64 with electrocautery (group B) by the same surgical team. Operative time, blood loss, total drainage volume and days, incidence of seroma, hematoma, pain score, and flap necrosis were recorded. Using Harmonic Focus significantly diminished operative time, blood loss, total drainage volume, days of stay, and visual analogue scale as compared with traditional electrocautery. There was no statistical difference between the 2 groups regarding seroma, hematoma, and flap necrosis. Axillary lymph node dissection using Harmonic Focus is feasible, safe, and a more comfortable design for the surgeon. Copyright © 2012 Elsevier Inc. All rights reserved.

Dosimetric assessment of static and helical TomoTherapy in the clinical implementation of breast cancer treatments.

PubMed

Reynders, Truus; Tournel, Koen; De Coninck, Peter; Heymann, Steve; Vinh-Hung, Vincent; Van Parijs, Hilde; Duchateau, Michaël; Linthout, Nadine; Gevaert, Thierry; Verellen, Dirk; Storme, Guy

2009-10-01

Investigation of the use of TomoTherapy and TomoDirect versus conventional radiotherapy for the treatment of post-operative breast carcinoma. This study concentrates on the evaluation of the planning protocol for the TomoTherapy and TomoDirect TPS, dose verification and the implementation of in vivo dosimetry. Eight patients with different breast cancer indications (left/right tumor, axillary nodes involvement (N+)/no nodes (N0), tumorectomy/mastectomy) were enrolled. TomoTherapy, TomoDirect and conventional plans were generated for prone and supine positions leading to six or seven plans per patient. Dose prescription was 42Gy in 15 fractions over 3weeks. Dose verification of a TomoTherapy plan is performed using TLDs and EDR2 film inside a home-made wax breast phantom fixed on a rando-alderson phantom. In vivo dosimetry was performed with TLDs. It is possible to create clinically acceptable plans with TomoTherapy and TomoDirect. TLD calibration protocol with a water equivalent phantom is accurate. TLD verification with the phantom shows measured over calculated ratios within 2.2% (PTV). An overresponse of the TLDs was observed in the low dose regions (<0.1Gy). The film measurements show good agreement for high and low dose regions inside the phantom. A sharp gradient can be created to the thoracic wall. In vivo dosimetry with TLDs was clinically feasible. The TomoTherapy and TomoDirect modalities can deliver dose distributions which the radiotherapist judges to be equal to or better than conventional treatment of breast carcinoma according to the organ to be protected.

Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression.

PubMed

Press, M F; Hung, G; Godolphin, W; Slamon, D J

1994-05-15

HER-2/neu oncogene amplification and overexpression of breast cancer tissue has been correlated with poor prognosis in women with both node-positive and node-negative disease. However, several studies have not confirmed this association. Review of these studies reveals the presence of considerable methodological variability including differences in study size, follow-up time, techniques and reagents. The majority of papers with clinical follow-up information are immunohistochemical studies using archival, paraffin-embedded breast cancers, and a variety of HER-2/neu antibodies have been used in these studies. Very little information, however, is available about the ability of the antibodies to detect overexpression following tissue processing for paraffin-embedding. Therefore, a series of antibodies, reported in the literature or commercially available, were evaluated to assess their sensitivity and specificity as immunohistochemical reagents. Paraffin-embedded samples of 187 breast cancers, previously characterized as frozen specimens for HER-2/neu amplification by Southern blot and for overexpression by Northern blot, Western blot, and immunohistochemistry, were used. Two multitumor paraffin-embedded tissue blocks were prepared from the previously analyzed breast cancers as a panel of cases to test a series of previously studied and/or commercially available anti-HER-2/neu antibodies. Immunohistochemical staining results obtained with 7 polyclonal and 21 monoclonal antibodies in sections from paraffin-embedded blocks of these breast cancers were compared. The ability of these antibodies to detect overexpression was extremely variable, providing an important explantation for the variable overexpression rate reported in the literature.

Patient navigation and the quality of breast cancer care: an analysis of the breast cancer care quality indicators.

PubMed

Weber, Joseph J; Mascarenhas, Debra C; Bellin, Lisa S; Raab, Rachel E; Wong, Jan H

2012-10-01

Patient navigation programs are initiated to help guide patients through barriers in a complex cancer care system. We sought to analyze the impact of our patient navigator program on the adherence to specific Breast Cancer Care Quality Indicators (BCCQI). A retrospective cohort of patients with stage I-III breast cancer seen the calendar year prior to the initiation of the patient navigation program were compared with patients treated in the ensuing two calendar years. Quality indicators deemed appropriate for analysis were those associated with overcoming barriers to treatment and those associated with providing health education and improving patient decision-making. A total of 134 consecutive patients between January 1, 2006 and December 31, 2006 and 234 consecutive patients between January 1, 2008 and December 31, 2009 were evaluated for compliance with the BCCQI. There was no significant difference in the mean age or race/ethnic distribution of the study population. In all ten BCCQI evaluated, there was improvement in the percentage of patients in compliance from pre and post implementation of a patient navigator program (range 2.5-27.0 %). Overall, compliance with BCCQI improved from 74.1 to 95.5 % (p < 0.0001). Indicators associated with informed decision-making and patient preference achieved statistical significance, while only completion axillary node dissection in sentinel node-positive biopsies in the process of treatment achieved statistical significance. The implementation of a patient navigator program improved breast cancer care as measured by BCCQI. The impact on disease-free and overall survival remains to be determined.

Navigation surgery for intraoperative sentinel lymph node detection using Indocyanine green (ICG) fluorescence real-time imaging in breast cancer.

PubMed

Toh, U; Iwakuma, N; Mishima, M; Okabe, M; Nakagawa, S; Akagi, Y

2015-09-01

A new sensitive fluorescence imaging system was developed for the real-time identification of sentinel lymph nodes (SLNs) in patients with early breast cancer. The purpose of this study was to evaluate the utility of a color charge-coupled device camera system for the intraoperative detection of SLNs and to determine its clinical efficacy and sensitivity in patients with operable breast cancer. We assessed a total of 168 patients diagnosed with or suspected of having early-stage breast cancer without metastasis in SLNs. The intraoperative detection of SLNs was performed using the conventional Indigo Carmine dye (indigotindisulfonate sodium) technique combined with a new Indocyanine green (ICG) imaging system (HyperEye Medical System: HEMS, MIZUHO IKAKOGYO, Japan) to map SLNs, in which the lymphatic vessels and SLNs were visualized transcutaneously with illuminating ICG fluorescence. Between January 2012 and May 2013, SLNs were successfully identified in all 168 patients (detection rate: 100%). By histopathology, the sensitivity was 93.8% for the detection of the metastatic involvement of SLNs (15 of 16 nodal-positive patients). After a median follow-up of 30.5 months, none of the patients presented with axillary recurrence. These results suggest that the HEMS imaging system is a feasible and effective method for the detection of SLNs in breast cancer. Furthermore, the HEMS device permitted the transcutaneous visualization of lymphatic vessels under light conditions, thus facilitating the identification and detection of SLNs without affecting the surgical procedure, together with a high sensitivity and specificity.

Mucinous cystadenocarcinoma of the breast.

PubMed

Koenig, C; Tavassoli, F A

1998-06-01

Four unusual cases of primary mammary mucinous cystadenocarcinoma composed predominantly of tall columnar cells with abundant intracytoplasmic mucin are reported; they were multicystic and appeared virtually identical to mucinous cystadenocarcinomas of the ovary and pancreas. Three of the women were white and one was black, they ranged in age from 49 to 67 years (average 58), and they had tumors that ranged from 0.8 to 19 cm in diameter. Microscopically, the tumors were characterized by cystic spaces lined by predominantly bland-appearing columnar mucinous cells with stratification, tufting, and papillary formations. Varying degrees of cytologic atypia were focally evident, with gradual loss of the intracytoplasmic mucin and transformation to an eosinophilic squamoid cell population. Multifocal invasion generally emanated from these eosinophilic, squamoid areas in all cases. All four tumors displayed immunoreactivity for MIB-1 (Ki-67) in a relatively high percentage of cells and failed to show immunoreactivity for estrogen receptors and progesterone receptors. All four stained positively with cytokeratin 7 (CK7) but were negative with cytokeratin 20 (CK20). Mastectomy and axillary lymph node dissection were performed in three cases and lumpectomy with lymph node dissection in the remaining case. Lymph node metastases, identified in only one patient, retained the distinctive morphology. Three of the patients are alive without evidence of disease 11, 22, and 24 months after the diagnosis; the fourth is a recent case. These tumors are a rare, clinicopathologically distinct type of primary breast carcinoma that should be distinguished from typical mucinous (colloid) carcinomas of the breast and, more importantly, metastases from other sites.

Detection of pAkt protein in imprint cytology of invasive breast cancer: Correlation with HER2/neu, hormone receptors, and other clinicopathological variables

PubMed Central

Vasou, Olympia; Skagias, Lazaros; Anastasia, Margariti; Paulina, Athanasiadou; Patsouris, Efstratios; Politi, Ekaterini

2015-01-01

Purpose: Akt is a serine/threonine protein kinase and has emerged as a crucial regulator of widely divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Activation of Akt/protein kinase B has been positively associated with human epidermal growth-factor receptor 2 (HER2)/neu overexpression in breast carcinoma and a worse outcome among endocrine treated patients. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Methods: Archival tumor tissues from 100 patients with invasive breast carcinoma were analyzed by immunocytochemistry. This study describes the results of immunocytochemical pAkt expression in breast carcinoma imprints, prepared from cut surfaces of freshly removed tumors. Both nuclear and cytoplasmic expressions were evaluated for pAkt. Results: Nuclear and cytoplasmic positive scores of 72% (72/100) and 42% (42/100), respectively, were found. Coexistence of nuclear and cytoplasmic staining was observed in 32 cases (32/100). Nuclear positive staining correlated with HER2/neu overexpression (P = 0.043) and was significantly associated with positive involvement of axillary lymph nodes (P = 0.013). No correlation was found between cytoplasmic pAkt rate and clinicopathological parameters, estrogen receptor, progesterone receptor or HER2/neu expression. Conclusions: pAkt expression can be evaluated in cytological material and may add valuable information to current prognostic models for breast cancer. pAkt overexpression appears to be linked with potentially aggressive tumor phenotype in invasive breast carcinoma. PMID:25838835

Tattoo pigment in axillary lymph node mimicking calcification of breast cancer

PubMed Central

Matsika, Admire; Srinivasan, Bhuvana; Gray, Janet Meryl; Galbraith, Christine Ruth

2013-01-01

A tattoo is defined as the intentional or accidental deposit of pigment into the skin. The phenomenon of skin tattooing is on the rise worldwide and complications of tattooing are increasingly being recognised in diagnostic and clinical medicine. We describe a case of calcification-like changes on mammography resembling that of breast malignancy as a result of tattoo pigment deposition in an axillary lymph node. Recognition of such changes in routine breast screening is crucial to avoid further unnecessary invasive investigations and surgery in such patients. PMID:23929611

Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis.

PubMed

Zhong, Jing-Min; Li, Jing; Kang, An-Ding; Huang, San-Qian; Liu, Wen-Bin; Zhang, Yun; Liu, Zhi-Hong; Zeng, Liang

2018-04-01

Breast cancer is the most common malignancy in females, with metastasis of this type of cancer frequently proving lethal. However, there are still no effective biomarkers to predict breast cancer metastasis. The aim of the present study was, therefore, to analyze breast cancer metastasis-associated proteins and evaluate the association between protein S100-A8 and the prognosis of breast cancer. The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technique was used to analyze the differential expression of proteins between fresh primary breast tumor (PBT) tissue and fresh paired metastatic lymph nodes (PMLN) tissue. Subsequently, immunohistochemical staining was used to locate and assess the expression of protein S100-A8 in benign breast disease (n=15), primary breast cancer with (n=109) or without (n=83) metastasis, and in paired metastatic lymph nodes (n=109) formalin fixed paraffin embedded (FFPE) tissue. Staining scores were evaluated and the association between protein S100-A8 expression levels and the clinicopathological characteristics of 192 patients with breast cancer were evaluated using the χ 2 test. Kaplan-Meier and Cox hazards regression analyses were utilized to investigate the association between the expression of protein S100-A8 and the prognosis of patients with breast cancer. A total of 4,837 proteins were identified using the iTRAQ proteomic technique. Among these proteins, 643 differentially expressed proteins were revealed. Protein S100-A8 expression levels were identified to differ between PBT and PMLN tissues. Immunohistochemical staining suggested a significant difference between NMBT and PMLN (P=0.002), and also between PBT and PMLN (P<0.001). Cox hazards regression model analyses suggested that histological grade (P=0.031) and nodal status (P=0.001) were risk factors for lymph nodes metastasis of breast cancer. Kaplan-Meier analyses revealed no significant relationship between protein S100-A8 expression level and overall survival rate of patients with breast cancer. In conclusion, by using the iTRAQ proteomic technique and immunohistochemistry staining, it was identified that protein S100-A8 may be associated with lymph nodes metastasis of breast cancer and be a marker for progression of breast cancer.

Tc-99m tilmanocept versus Tc-99m sulfur colloid in breast cancer sentinel lymph node identification: Results from a randomized, blinded clinical trial.

PubMed

Unkart, Jonathan T; Hosseini, Ava; Wallace, Anne M

2017-12-01

No prior trials have compared sentinel lymph node (SLN) identification outcomes between Tc-99m tilmanocept (TcTM) and Tc-99m sulfur colloid (TcSC) in breast cancer (BC). We report on the secondary outcomes from a randomized, double-blinded, single surgeon clinical trial comparing post-injection site pain between TcTM and TcSC. Patients were randomized to receive a preoperative single, peritumoral intradermal injection of TcTM or TcSC. The number of total, "hot", and blue nodes detected and removed were compared between groups. Fifty-two (27-TcSC and 25-TcTM) patients were enrolled and underwent definitive surgical treatment. At least one "hot" SLN was detected in all patients. Three (5.8%) patients had a disease positive-SLN. The total number of SLNs removed was 61 (mean 2.26 (standard deviation (SD) 0.90)) in the TcSC group and 54 (mean 2.16 (SD 0.90)) in the TcTM group, P = 0.69. The total number of "hot" nodes in the TcSC group was 1.96 (SD 0.76) compared to 2.04 (SD 0.73) in the TcTM group, P = 0.71. The number of identified SLNs did not differ significantly between TcTM and TcSC. Given that no significant technical advantages exist between the two agents, surgeons should choose a radiopharmaceutical based on cost and side effect profile. © 2017 Wiley Periodicals, Inc.

The expression of MCM-2 in invasive breast carcinoma: a stereologic approach.

PubMed

Cobanoglu, Umit; Mungan, Sevdegul; Gundogdu, Cemal; Ersoz, Safak; Ozoran, Yavuz; Aydin, Fazil

2010-01-01

The aim of this study is to examine the expression of MCM-2 and conventional proliferation marker Ki-67 in breast carcinoma by stereologic technique and to compare it with various clinicopathologic parameters. The expression of MCM-2 and Ki-67 on paraffin-embedded tumor tissue sections of patients with invasive breast carcinoma was analyzed immunohistochemically. Stereologic method was used for evaluation of the percentage of positively stained tumor cells. Significant positive correlation was found between the expression of MCM-2 and that of Ki-67 (r = 0.74, p < 0.001). MCM-2 and Ki-67 expression was significantly associated with histologic grade (p < 0.05), and negative correlation was observed between MCM-2 or Ki-67 expression and estrogen status (p < 0.05). No significant association was observed between MCM-2 or Ki-67 expression and patient age, tumor size, lymph node status, clinical stage and menopausal status. Our results suggest that MCM-2 expression is significantly associated with histologic grade of breast carcinoma and with cell proliferation capacity (Ki-67 labelling index). Additional studies are required using the stereologic method to compare and understand the utility of Ki-67 and MCM-2 expression in invasive breast carcinoma (Tab. 1, Fig. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.

Meeting highlights--International Consensus Panel on the treatment of primary breast cancer.

PubMed

Taguchi, Tetsuo

2002-03-01

The 7th International Conference on Adjuvant Therapy of Primary Breast Cancer, with several thousand delegates from 70 countries, was held in February 2001 in St. Gallen, Switzerland. Its consensus recommendations were summarized in the Sept. 15 issue of the Journal of Clinical Oncology (Vol. 19, No. 18, 2001: pp 3817-3827). The panel conference developed guidelines advising that all patients with endocrine-responsive tumors receive anti-hormonal therapy, including those at minimal risk of recurrence (defined as a 10% risk at 10 years). The panel further lowered the threshold defining endocrine-responsive disease to tumors containing as few as 1% of cells that stain positive for steroid hormone receptors. Treatment of primary breast cancer should depend on the hormonal status of tumors. The last set of guidelines, issued in 1998, supported a more limited use of endocrine-based therapy, but recent research has convinced the oncology community otherwise. Postmenopausal women have the greatest prevalence of hormone-positive tumors, and more than one-third of breast cancers in women of child-bearing age are estrogen dependent. The panel also highlighted several other important advances, including: the importance of factoring patient preferences into treatment decisions; the value of sentinel lymph node biopsy in avoiding extensive surgery; and incorporation of new agents and improved outcome in the treatment of breast cancer.

ZEB1 expression is correlated with tumor metastasis and reduced prognosis of breast carcinoma in Asian patients.

PubMed

Xiang, Shuai; Liu, Ya-Min; Chen, Xu; Wang, Ya-Wen; Ma, Ran-Ran; Wu, Xiao-Juan; Gao, Peng

2015-07-01

Tumor metastasis is one of the key events leading to tumor relapse and poor prognosis. Nowadays, increasing evidences demonstrated that ZEB1 was implicated in human carcinogenesis. However, involvement of ZEB1 deregulation in tumorigenesis in Asian patients with breast carcinoma remains elusive. The present study included 102 Asian patients with breast carcinoma treated by surgery from January of 2005 to December of 2006, and the expression of ZEB1 was evaluated by immunohistochemistry. To further assess the prognostic value of ZEB1, Kaplan-Meier curves were constructed. In this study, elevated levels of ZEB1 expression was found in carcinomas with higher aggressive potential. We also correlated expression of ZEB1 with lymph node metastasis (P = 0.021), advanced clinical stage (P = 0.012) in all cases, and high tumor grade (P = 0.047) in invasive ductal carcinoma. Furthermore, our data suggested an elevated level of Ki-67 expression in cases with positive expression of ZEB1. Clinically, reduced overall survival and disease-free survival were observed in cases with positive ZEB1 expression than that in negative cases. Our results correlated ZEB1 with aggressive potentials of breast carcinoma and revealed a possibility for ZEB1 as a prognostic marker in breast carcinoma.

Intracellular esterase activity in living cells may distinguish between metastatic and tumor-free lymph nodes.

PubMed

Afrimzon, Elena; Deutsch, Assaf; Shafran, Yana; Zurgil, Naomi; Sandbank, Judith; Pappo, Itzhak; Deutsch, Mordechai

2008-01-01

One of the major clinical problems in breast cancer detection is the relatively high incidence of occult lymph node metastases undetectable by standard procedures. Since the ascertainment of breast cancer stage determines the following treatment, such a "hypo-diagnosis" leads to inadequate therapy, and hence is detrimental for the outcome and survival of the patients. The purpose of our study was to investigate functional metabolic characteristics of living cells derived from metastatic and tumor-free lymph nodes of breast cancer (BC) patients. Our methodology is based on the ability of living cells to hydrolyze fluorescein diacetate (FDA) by intracellular esterases and on the association of FDA hydrolysis rates with a specific cell status, both in physiological and pathological conditions. The present study demonstrates a significant difference in the ability to utilize FDA by lymph node cells derived from metastatic and tumor-free lymph nodes in general average, as well as in the metastatic and tumor-free lymph nodes of individual patients. Cells from metastatic lymph nodes had a higher capacity for FDA hydrolysis, and increased this activity after additional activation by autologous tumor tissue (tt). The association between increased FDA hydrolysis rate and activated T lymphocytes and antigen-presenting cells (APC) was shown. The results of the present study may contribute to predicting the risk of involvement of seemingly "tumor-free" axillary lymph nodes in occult metastatic processes, and to reducing false-negative results of axillary examination.

Clinical and histopathological factors affecting failed sentinel node localization in axillary staging for breast cancer.

PubMed

Dordea, Matei; Colvin, Hugh; Cox, Phil; Pujol Nicolas, Andrea; Kanakala, Venkat; Iwuchukwu, Obi

2013-04-01

Sentinel lymph node biopsy (SLNB) has become the standard of care in axillary staging of clinically node-negative breast cancer patients. To analyze reasons for failure of SLN localization by means of a multivariate analysis of clinical and histopathological factors. We performed a review of 164 consecutive breast cancer patients who underwent SLNB. A superficial injection technique was used. 9/164 patients failed to show nodes. In 7/9 patients no evidence of radioactivity or blue dye was observed. Age and nodal status were the only statistically significant factors (p < 0.05). For every unit increase in age there was a 9% reduced chance of failed SLN localization. Patients with negative nodal status have 90% reduced risk of failed sentinel node localization than patients with macro or extra capsular nodal invasion. The results suggest that altered lymphatic dynamics secondary to tumour burden may play a role in failed sentinel node localization. We showed that in all failed localizations the radiocolloid persisted around the injection site, showing limited local diffusion only. While clinical and histopathological data may provide some clues as to why sentinel node localization fails, we further hypothesize that integrity of peri-areolar lymphatics is important for successful localization. Copyright © 2012 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.

PubMed

Deng, Yunte; Xue, Debin; Wang, Xiaoyan; Xu, Sanpeng; Ao, Qilin; Hu, Zhiyong; Wang, Guoping

2012-06-01

Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype. © 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method.

PubMed

Otsubo, Ryota; Oikawa, Masahiro; Hirakawa, Hiroshi; Shibata, Kenichiro; Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe; Shigematsu, Kazuto; Hatachi, Toshiko; Yano, Hiroshi; Matsumoto, Megumi; Takagi, Katsunori; Tsuchiya, Tomoshi; Tomoshige, Koichi; Nakashima, Masahiro; Taniguchi, Hideki; Omagari, Takeyuki; Itoyanagi, Noriaki; Nagayasu, Takeshi

2014-02-15

We developed an easy, quick and cost-effective detection method for lymph node metastasis called the semi-dry dot-blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti-pancytokeratin antibody, modifying dot-blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity and accuracy of the SDB method were 100, 98.0 and 98.3%, respectively (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node-negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2-mm intervals and the sensitivity, specificity, accuracy and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy and mean required time of the SDB method were 93.3, 96.9, 96.6 and 43.3 min, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis. © 2013 UICC.

Histologic pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

PubMed Central

Ko, Jennifer S; Prieto, Victor G; Elson, Paul; Vilain, Ricardo E; Pulitzer, Melissa; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa; Ernstoff, Marc S; Gastman, Brian; Billings, Steven D

2016-01-01

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathologic predictors of outcome were sought. Five metastatic patterns were identified: 1, sheet-like (n=38, 59%); 2, non-solid parafollicular (n=4, 6%); 3, sinusoidal, (n=11, 17%); 4, perivascular hilar (n=1, 2%) and 5, rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21(33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2–5 metastases (p=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. 3 (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. 4 (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph node (1 or 2 versus >2, p<.0001), age (<70 versus ≥70, p=.01), sentinel lymph node metastasis pattern (patterns 2–5 versus 1, p=.02), and immune status (immunocompetent versus suppressed, p=.03) were independent predictors of outcome, and could be used to stratify Stage III patients into 3 groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathologic features facilitates risk stratification of Merkel cell carcinoma patients that may have management implications. PMID:26541273

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

PubMed

Ko, Jennifer S; Prieto, Victor G; Elson, Paul J; Vilain, Ricardo E; Pulitzer, Melissa P; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa P; Ernstoff, Marc S; Gastman, Brian R; Billings, Steven D

2016-02-01

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

Perigastric lymph node metastasis from papillary thyroid carcinoma in a patient with early gastric cancer: the first case report.

PubMed

Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok

2014-09-01

Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.

Feasibility and toxicity of docetaxel before or after fluorouracil, epirubicin and cyclophosphamide as adjuvant chemotherapy for early breast cancer.

PubMed

Abe, Hajime; Mori, Tsuyoshi; Kawai, Yuki; Cho, Hirotomi; Kubota, Yoshihiro; Umeda, Tomoko; Kurumi, Yoshimasa; Tani, Tohru

2013-06-01

The tolerance and safety associated with the administration order of the anthracycline and taxane drugs have not been evaluated. Breast cancer patients with node-positive or high-risk patients with node-negative were eligible. The feasibility and toxicity were evaluated in the following regimens--arm A, 3 courses of fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) followed by 3 courses of docetaxel 100 mg/m(2) (DOC); arm B, 3 courses of DOC followed by 3 courses of FEC. Forty-two patients were registered. The relative dose intensity was 94.2 % for FEC and 97.8 % for DOC in arm A, and 98.9 % for DOC and 95.2 % for FEC in arm B. In arm A, grade 3 or higher hematological toxicity was observed in nine patients, and febrile neutropenia developed in three patients with FEC. In arm B, grade 3 or higher hematological toxicity was observed in seven patients, but febrile neutropenia was not noted in any patient. The regimens in both arms A and B were safe regarding adjuvant chemotherapy for early breast cancer. However, DOC followed by FEC might be more tolerable. Further studies will maximize the results obtained with DOC followed by FEC.

Cost-effectiveness of adjuvant docetaxel for node-positive breast cancer patients: results of the PACS 01 economic study.

PubMed

Marino, P; Siani, C; Roché, H; Protière, C; Fumoleau, P; Spielmann, M; Martin, A-L; Viens, P; Le Corroller Soriano, A-G

2010-07-01

Using data from the PACS 01 randomized trial, we evaluated the cost-effectiveness of anthracyclines plus docetaxel (Taxotere; FEC-D) versus anthracyclines alone (FEC100) in patients with node-positive breast cancer. Costs and outcomes were assessed in 1996 patients and the incremental cost-effectiveness ratios (ICERs) were estimated, using quality-adjusted life years (QALYs) as outcome. To deal with uncertainty due to sampling fluctuations, confidence regions around the ICERs were calculated and cost-effectiveness acceptability curves were drawn up. Sensitivity analyses were also carried out to assess the robustness of conclusions. The mean cost of treatment was 33% higher with strategy FEC-D, but this difference decreased to 18% at a 5-year horizon. The ICER of FEC-D versus FEC100 was estimated to be 9665euro per QALY gained (95% confidence interval euro2372-euro55 515). The estimated probability that FEC-D was cost-effective reached >96% for a threshold of euro50 000 per QALY gained. If the price of taxane decreased slightly, the ICER would reach some very reasonable levels and this strategy would therefore be much more cost-effective. The sequential use of FEC100 followed by docetaxel appears to be a cost-effective alternative, even when uncertainty is taken into account.

Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer

PubMed Central

Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin

2016-01-01

An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20–24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice. PMID:27374088

Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer.

PubMed

Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin; Yu, Jin-Ming; Wang, Yong-Sheng

2016-07-26

An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20-24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice.

Lymphadenopathy resulting from acute toxoplasmosis mimicking relapse of non-Hodgkin's lymphoma on fluorodeoxyglucose positron emission tomography/computed tomography.

PubMed

Joshi, Prathamesh; Lele, Vikram; Mahajan, Pravin

2012-01-01

We report a case documenting fluorodeoxyglucose (FDG) accumulation in cervical, supraclavicular and axillary lymph nodes resulting from acute toxoplasmosis. A 50-year-old Indian female with history of non-Hodgkin's lymphoma (NHL) of left breast, postchemotherapy status, was found to have hypermetabolic right cervical, supraclavicular and axillary lymph nodes on a surveillance FDG positron emission tomography/computed tomography (PET/CT) scan. Her previous two PET/CT scans were unremarkable with no evidence of metabolically active disease. Therefore, a differential diagnosis of relapse of NHL versus infectious/inflammatory pathology was raised in the report. Biopsy of axillary lymph node demonstrated features characteristic of toxoplasmosis. The serological test results were also compatible with acute toxoplasmosis infection. Infective and inflammatory diseases are known to accumulate FDG, resulting in false positives for malignancy. This case demonstrates lymph nodal toxoplasmosis as a potential cause of false positive FDG PET/CT findings in patients with known malignancy and highlights the importance of histopathological and laboratory correlation for the accurate interpretation of FDG PET/CT scans.

Characteristics of axillary lymph nodes apparent on dynamic contrast-enhanced breast MRI in healthy women.

PubMed

Krammer, Julia; Engel, Dorothee; Nissen, Johanna; Schnitzer, Andreas; Suetterlin, Marc; Schoenberg, Stefan O; Wasser, Klaus

2012-01-01

The study was initiated to characterize and better understand the natural characteristics of axillary lymph nodes (LNs) apparent on dynamic breast magnetic resonance imaging (MRI). The most important finding in 71 subjects that included healthy women was that 41% showed strong enhanced axillary LNs. The dynamic curves of these LNs revealed an initial mean signal increase of 197% (±58%), all of them with a following plateau (34%) or washout (66%). Our study points out that the previous understanding of contrast enhancement in breast lesions should be taken with care when assessing axillary LNs. This has to be considered especially in preoperative breast MRI. Copyright © 2012 Elsevier Inc. All rights reserved.

Sentinel lymph node biopsy under fluorescent indocyanin green guidance: Initial experience

PubMed Central

Aydoğan, Fatih; Arıkan, Akif Enes; Aytaç, Erman; Velidedeoğlu, Mehmet; Yılmaz, Mehmet Halit; Sager, Muhammet Sait; Çelik, Varol; Uras, Cihan

2016-01-01

Objective: Sentinel lymph node biopsy can be applied by using either blue dye or radionuclide method or both in breast cancer. Fluorescent imaging with indocyanine green is a new defined method. This study evaluates the applicability of sentinel lymph node biopsy via fluorescent indocyanine green. Material and Methods: IC-VIEW (Pulsion Medical Systems AG, Munich, Germany) infrared visualization system was used for imaging. Two mL of indocyanine green was injected to visualize sentinel lymph nodes. After injection, subcutaneous lymphatics were traced and sentinel lymph nodes were found with simultaneous imaging. Sentinel lymph nodes were excised under fluorescent light guidance, and excised lymph nodes were examined histopathologically. Patients with sentinel lymph node metastases underwent axillary dissection. Results: Four patients with sentinel lymph node biopsy due to breast cancer were included in the study. Sentinel lymph nodes were visualized with indocyanine green in all patients. The median number of excised sentinel lymph node was 2 (2–3). Two patients with lymph node metastasis underwent axillary dissection. No metastasis was detected in lymph nodes other than the sentinel nodes in patients with axillary dissection. There was no complication during and after the operation related to the method. Conclusion: According to our limited experience, sentinel lymph node biopsy under fluorescent indocyanine green guidance, which has an advantage of simultaneous visualization, is technically feasible. PMID:26985159

Delineating Extramammary Findings at Breast MR Imaging.

PubMed

Gao, Yiming; Ibidapo, Opeyemi; Toth, Hildegard K; Moy, Linda

2017-01-01

Breast magnetic resonance (MR) imaging is the only breast imaging modality that consistently encompasses extramammary structures in the thorax and upper abdomen. Incidental extramammary findings on breast MR images of patients with a history of breast cancer or other malignancies are significantly more likely to be malignant and may affect staging and treatment. An understanding of the frequency, distribution, and context of extramammary findings on breast MR images and a familiarity with common and uncommon sites of breast cancer metastasis inform the differential diagnosis and prompt the appropriate diagnostic next step, to differentiate benign from malignant findings. High-yield organ systems on breast MR images, as reflected by a high positive predictive value for malignancy, are correlated with known distant sites of breast cancer metastasis in the bone, lung, liver, and lymph nodes. Staging is considered when disease involves the skin and chest wall. Unusual sites of breast cancer metastasis from invasive lobular carcinoma are discussed, including the gastrointestinal tract, peritoneum, and adrenal glands. Nonmalignant clinically important findings involving the cardiovascular and gastrointestinal systems are reviewed, and potential pitfalls in diagnosis and interpretation are highlighted. A consistently systematic diagnostic approach is emphasized for identifying extramammary abnormalities on breast MR images. All things considered, the radiologist should be able to improve diagnostic sensitivity and specificity while interpreting extramammary findings on breast MR images. © RSNA, 2017.

Cost-effectiveness of the 21-gene recurrence score assay in the context of multifactorial decision making to guide chemotherapy for early-stage breast cancer.

PubMed

Reed, Shelby D; Dinan, Michaela A; Schulman, Kevin A; Lyman, Gary H

2013-03-01

New evidence is available regarding the utility of the 21-gene recurrence score assay in guiding chemotherapy use for node-negative, estrogen receptor-positive breast cancer. We applied this evidence in a decision-analytic model to re-evaluate the cost-effectiveness of the assay. We cross-classified patients by clinicopathologic characteristics from the Adjuvant! risk index and by recurrence score risk group. For non-recurrence score-guided treatment, we assumed patients receiving hormonal therapy alone had low-risk characteristics and patients receiving chemotherapy and hormonal therapy had higher-risk characteristics. For recurrence score-guided treatment, we assigned chemotherapy probabilities conditional on recurrence score risk group and clinicopathologic characteristics. An estimated 40.4% of patients in the recurrence score-guided strategy and 47.3% in the non-recurrence score-guided strategy were expected to receive chemotherapy. The incremental gain in quality-adjusted life-years was 0.16 (95% confidence interval, 0.08-0.28) with the recurrence score-guided strategy. Lifetime medical costs to the health system were $2,692 ($1,546-$3,821) higher with the recurrence score-guided strategy, for an incremental cost-effectiveness ratio of $16,677/quality-adjusted life-year ($7,613-$37,219). From a societal perspective, the incremental cost-effectiveness was $10,788/quality-adjusted life-year ($6,840-$30,265). The findings provide supportive evidence for the economic value of the 21-gene recurrence score assay in node-negative, estrogen receptor-positive breast cancer.

A case of gastric cancer metastasis to the breast in a female with BRCA2 germline mutation and literature review.

PubMed

Dulskas, Audrius; Al Bandar, Mahdi; Choi, Yoon Young; Shin, Su-Jin; Beom, Seung-Hoon; Son, Taeil; Kim, Hyung-Il; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon

2017-12-05

Gastric cancer is a deadly disease. Common sites of distant metastasis of gastric cancer are the peritoneum, liver, lymph nodes, and lung. The breast is a rare site of metastasis in gastric cancer which occurs in males dominantly. Here, we report the first case of metastatic gastric cancer to the breast in a patient with the breast cancer 2 (BRCA2) germline mutation. A 34-year-old female was admitted to the hospital with dyspepsia and a palpable mass in the left breast. Gastric cancer was confirmed to be signet ring cell adenocarcinoma. The breast mass exhibited histological properties consistent with gastric cancer. Immunohistochemistry results showed the breast tumor was CDX-2 and CK20-positive, but ER-, CK7-, and GATA3-negative. The BRCA1 gene had a wild-type sequence, but a heterozygous variant was discovered in BRCA2 in exon 10 (c.1744A > C, p.T582P); the significance of this variant is unknown. The patient received palliative XELOX (capecitabine + oxaliplatin) with radiation therapy to the stomach. The breast tumor resolved completely, but the overall response was partial. Gastric cancer metastasis to the breast is rare, but should be considered in young female patients with signet ring cell type gastric cancer.

Diagnostic and prognostic value of plasma and tissue ubiquitin-like, containing PHD and RING finger domains 1 in breast cancer patients.

PubMed

Geng, Yao; Gao, Yanfang; Ju, Huangxian; Yan, Feng

2013-02-01

Ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) has been reported to play an important role in breast carcinogenesis. This work investigated the correlation of UHRF1 DNA level in plasma with clinical characteristics of breast cancer and its clinical significance in breast cancer diagnosis. The expression of UHRF1 in primary breast cancer tissue was examined by Western blot. The UHRF1 DNA levels in plasma and UHRF1 mRNA expression in tissues were determined by accurate real-time quantitative PCR. The associations of UHRF1 levels with clinical variables were evaluated using standard statistical methods. The UHRF1 DNA in plasma of 229 breast cancer patients showed higher expression than healthy controls, which showed high specificity up to 76.2% at a sensitivity of 79.2%, and was significantly associated with c-erbB2 positive status, cancer stage and lymph node metastasis. High UHRF1 DNA level in plasma was significantly associated with short progression-free survival. The UHRF1 DNA level in plasma is highly correlative with breast cancer and its status and stage, and may be a potential independent diagnostic and prognostic factor for both breast cancer and the survival of breast cancer patients. © 2012 Japanese Cancer Association.

The crossroads of breast cancer progression: insights into the modulation of major signaling pathways

PubMed Central

Farias, Jessica O; Torres, Nadia EC; Ferruzo, Pault YM; Anschau, Valesca; Jesus-Ferreira, Henrique C; Chang, Ted Hung-Tse; Sogayar, Mari Cleide; Zerbini, Luiz F; Correa, Ricardo G

2017-01-01

Cancer is the disease with highest public health impact in developed countries. Particularly, breast cancer has the highest incidence in women worldwide and the fifth highest mortality in the globe, imposing a significant social and economic burden to society. The disease has a complex heterogeneous etiology, being associated with several risk factors that range from lifestyle to age and family history. Breast cancer is usually classified according to the site of tumor occurrence and gene expression profiling. Although mutations in a few key genes, such as BRCA1 and BRCA2, are associated with high breast cancer risk, the large majority of breast cancer cases are related to mutated genes of low penetrance, which are frequently altered in the whole population. Therefore, understanding the molecular basis of breast cancer, including the several deregulated genes and related pathways linked to this pathology, is essential to ensure advances in early tumor detection and prevention. In this review, we outline key cellular pathways whose deregulation has been associated with breast cancer, leading to alterations in cell proliferation, apoptosis, and the delicate hormonal balance of breast tissue cells. Therefore, here we describe some potential breast cancer-related nodes and signaling concepts linked to the disease, which can be positively translated into novel therapeutic approaches and predictive biomarkers. PMID:29200866

Limited effectiveness of patent blue dye in addition to isotope scanning for identification of sentinel lymph nodes: Cross-sectional real-life study in 1024 breast cancer patients.

PubMed

Rauch, Philippe; Merlin, Jean-Louis; Leufflen, Lea; Salleron, Julia; Harlé, Alexandre; Olivier, Pierre; Marchal, Frédéric

2016-09-01

Although morbidity is reduced when sentinel lymph node (SLN) biopsy is performed with dual isotopic and blue dye identification, the effectiveness of adding blue dye to radioisotope remains debated because side effects including anaphylactic reactions. Using data from a prospectively maintained database, 1884 lymph node-negative breast cancer patients who underwent partial mastectomy with SLN mapping by a dual-tracer using patent blue dye (PBD) and radioisotope were retrospectively studied between January 2000 and July 2013. Patients with tumors <3 cm and with >1 node detected by one of the two techniques (N = 1024) were included in this real-life cross-sectional study. Among the 1024 patients, 274 had positive SLN detected by isotopic and/or PBD staining. Only 4 patients having no detectable radioactivity in the axilla had SLN identified only by PBD staining (blue-only) while 26 patients had SLN only identified by isotopic detection (hot-only) illustrating failure rates of 9.5% (26/274) and 1.5% (4/274), respectively. Among these four patients, two had negative lymphoscintigraphy. Therefore, the contribution of PBD to metastatic nodes identification was relevant for only 2/274 patients (0.8%). Three patients (0.3%) had an allergic reaction with PBD, and anaphylactic shock occurred in two cases (0.2%). The added-value of PBD to reduce the false-negative rate of SLN mapping is only limited to the rare cases in which no radioactivity is detectable in the axilla (<1%). When a radioisotope mapping agent is available, the use of PBD should be avoided, because it can induce anaphylaxis. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Lack of influence of cytokeratin-positive mini micrometastases in "Negative Node" patients with colorectal cancer: findings from the national surgical adjuvant breast and bowel projects protocols R-01 and C-01.

PubMed

Fisher, Edwin R; Colangelo, Linda; Wieand, Samuel; Fisher, Bernard; Wolmark, Norman

2003-08-01

Results of the few extant reports concerning the clinical significance of so-called "occult micrometastases" of lymph nodes of patients with Dukes A and B colorectal cancer have been variable. We examined the presumably negative nodes of a larger cohort of such patients who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trials R-01 and C-01 for the influence of what we preferably designate as nodal mini micrometastases on parameters of survival. Mini micrometastases were detected by immunohistochemical staining of the original lymph node sections with anticytokeratin A1/A3 in a total of 241 Dukes A and B patients with rectal and 158 with colonic cancers. Their frequency, as well as that of nuclear and histologic grades, and an estimation of their relationship to relative risks were correlated with overall and recurrence-free survival by univariate and multivariate analyses. Nodal mini micrometastases were detected in 73 of 399 (18.3 percent) patients of this cohort. They failed to exhibit any significant relationship to overall or recurrence-free survival. No association between the assessments of tumor differentiation and mini micrometastases was found. Nuclear and histologic grades also failed to further discriminate overall or recurrence-free survival in patients with A or B stages of colonic or rectal cancers in this cohort. The immunohistochemical demonstration of nodal mini micrometastases failed to discriminate high- and low-risk groups of patients with colorectal cancer who were designated as being node-negative after routine pathologic examination.

SU-F-T-520: Dosimetric Comparison of Radiation Treatment Plans for Whole Breast Irradiation Between 3D Conformal in Prone and Supine Positions Vs. VMAT and IMRT in Supine Positions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bejarano Buele, A; Parsai, E

Purpose: The target volume for Whole Breast Irradiation (WBI) is dictated by location of tumor mass, breast tissue distribution, and involvement of lymph nodes. Dose coverage and Organs at Risk (OARs) sparing can be difficult to achieve in patients with unfavorable thoracic geometries. For these cases, inverse-planned and 3D-conformal prone treatments can be alternatives to traditional supine 3D-conformal plans. A dosimetric comparison can determine which of these techniques achieve optimal target coverage while sparing OARs. Methods: This study included simulation datasets for 8 patients, 5 of whom were simulated in both supine and prone positions. Positioning devices included breast boardsmore » and Vaclok bags for the supine position, and prone breast boards for the prone position. WBI 3-D conformal plans were created for patients simulated in both positions. Additional VMAT and IMRT WBI plans were made for all patients in the supine position. Results: Prone and supine 3D conformal plans had comparable PTV coverage. Prone 3D conformal plans received a significant 50% decrease to V20, V10, V5 and V30% for the ipsilateral lung in contrast to the supine plans. The heart also experienced a 10% decrease in maximum dose in the prone position, and V20, V10, V5 and V2 had significantly lower values than the supine plan. Supine IMRT and VMAT breast plans obtained comparable PTV coverage. The heart experienced a 10% decrease in maximum dose with inverse modulated plans when compared to the supine 3D conformal plan, while V20, V10, V5 and V2 showed higher values with inverse modulated plans than with supine 3D conformal plans. Conclusion: Prone 3D-conformal, and supine inverse planned treatments were generally superior in sparing OARs to supine plans with comparable PTV coverage. IMRT and VMAT plans offer sparing of OARs from high dose regions with an increase of irradiated volume in the low dose regions.« less

Epidermal growth factor receptor (EGFr); results of a 6 year follow-up study in operable breast cancer with emphasis on the node negative subgroup.

PubMed Central

Nicholson, S.; Richard, J.; Sainsbury, C.; Halcrow, P.; Kelly, P.; Angus, B.; Wright, C.; Henry, J.; Farndon, J. R.; Harris, A. L.

1991-01-01

More accurate criteria are required for the selection of patients with node-negative breast cancer for systemic adjuvant therapy. Expression of epidermal growth factor receptor (EGFr) has been shown previously to be inversely related to oestrogen receptor (ER) in patients with operable breast cancer and to be associated with a poorer prognosis. Analysis of EGFr and ER was performed on tumour samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumours with greater than 10 fmol mg-1 I125-EGF binding (EGFr+) and 47% (109) and cystolic ER concentrations greater than 5 fmol mg-1 (ER+), with a marked inverse relationship between EGFr and ER (P less than 0.00001). In a univariate analysis EGFr was second only to axillary node status as a prognostic marker for all patients both in terms of relapse-free and overall survival (P less than 0.001, log rank). For patients with histologically negative axillary nodes EGFr was superior to ER in predicting relapse and survival (P less than 0.01 and P less than 0.005 respectively compared to P less than 0.1 and P less than 0.1, log rank). In a multivariate (Cox model) analysis only EGFr, out of EGFr, ER, size and grade, was predictive for either relapse-free or overall survival for patients with node-negative disease (P = 0.05 and P = 0.026 respectively). EGFr has been shown to be a marker of poor prognosis for patients with node-negative breast cancer. Since patients with EGFr+ tumours are unlikely to respond to hormone therapy it may be possible to select them for trials of systemic adjuvant chemotherapy. PMID:1846551

Epidermal growth factor receptor (EGFr); results of a 6 year follow-up study in operable breast cancer with emphasis on the node negative subgroup.

PubMed

Nicholson, S; Richard, J; Sainsbury, C; Halcrow, P; Kelly, P; Angus, B; Wright, C; Henry, J; Farndon, J R; Harris, A L

1991-01-01

More accurate criteria are required for the selection of patients with node-negative breast cancer for systemic adjuvant therapy. Expression of epidermal growth factor receptor (EGFr) has been shown previously to be inversely related to oestrogen receptor (ER) in patients with operable breast cancer and to be associated with a poorer prognosis. Analysis of EGFr and ER was performed on tumour samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumours with greater than 10 fmol mg-1 I125-EGF binding (EGFr+) and 47% (109) and cystolic ER concentrations greater than 5 fmol mg-1 (ER+), with a marked inverse relationship between EGFr and ER (P less than 0.00001). In a univariate analysis EGFr was second only to axillary node status as a prognostic marker for all patients both in terms of relapse-free and overall survival (P less than 0.001, log rank). For patients with histologically negative axillary nodes EGFr was superior to ER in predicting relapse and survival (P less than 0.01 and P less than 0.005 respectively compared to P less than 0.1 and P less than 0.1, log rank). In a multivariate (Cox model) analysis only EGFr, out of EGFr, ER, size and grade, was predictive for either relapse-free or overall survival for patients with node-negative disease (P = 0.05 and P = 0.026 respectively). EGFr has been shown to be a marker of poor prognosis for patients with node-negative breast cancer. Since patients with EGFr+ tumours are unlikely to respond to hormone therapy it may be possible to select them for trials of systemic adjuvant chemotherapy.

The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).

PubMed

Penault-Llorca, Frédérique; Filleron, Thomas; Asselain, Bernard; Baehner, Frederick L; Fumoleau, Pierre; Lacroix-Triki, Magali; Anderson, Joseph M; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Roca, Lise; Sagan, Christine; Lemonnier, Jérôme; Martin, Anne-Laure; Roché, Henri

2018-05-04

The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Not applicable.

[Clinicopathologic characteristics and prognosis in young Chinese women with breast cancer].

PubMed

Liu, Xin; Liu, Qi-feng; Xu, Ye; Ouyang, Tao; Li, Jin-feng; Wang, Tian-feng; Fan, Zhao-qing; Fan, Tie; Lin, Ben-yao; Xie, Yun-tao

2011-07-12

To analyze the clinicopathologic characteristics and evaluate the prognosis in young Chinese women with breast cancer. A total of 1538 female patients with operable primary breast cancer (stage I-III) treated at our hospital from December 1994 to December 2003 were analyzed retrospectively. Among them, 1075 patients (≤ 60 yrs) with the complete follow-up data were divided into two groups according to age: young breast cancer group (≤ 40 yrs, n = 208) and control group (41 - 60 yrs, n = 867) to analyze the differences in their clinicopathologic characteristics and evaluate the prognosis of both groups. The patients with young breast cancer were more likely to have positive lymph nodes (P = 0.016), a negative expression of ER (estrogen receptor) (P = 0.016) and a positive expression of HER2 (P = 0.001). The 5-year disease-free survival (DFS) rates of young breast cancer group and control group were 73.3% and 84.1% (P < 0.001) and the 5-year overall survival (OS) rates 83.5% and 89.1% (P = 0.004) respectively. Moreover, the patients with young breast cancer had a worse DFS than control group in patients with stage I-II disease but not in those with stage III disease. And ≤ 40 years was an independent unfavorable prognostic factor of DFS (HR = 1.78, 95%CI: 1.19 - 2.66, P = 0.005) and OS (HR = 1.71, 95%CI: 1.01 - 2.90, P = 0.046) in the patients with stage I-II disease. Chinese women with young breast cancer have a worse prognosis, particularly in those with stage I-II disease.

Association between US features of primary tumor and axillary lymph node metastasis in patients with clinical T1-T2N0 breast cancer.

PubMed

Bae, Min Sun; Shin, Sung Ui; Song, Sung Eun; Ryu, Han Suk; Han, Wonshik; Moon, Woo Kyung

2018-04-01

Background Most patients with early-stage breast cancer have clinically negative lymph nodes (LNs). However, 15-20% of patients have axillary nodal metastasis based on the sentinel LN biopsy. Purpose To assess whether ultrasound (US) features of a primary tumor are associated with axillary LN metastasis in patients with clinical T1-T2N0 breast cancer. Material and Methods This retrospective study included 138 consecutive patients (median age = 51 years; age range = 27-78 years) who underwent breast surgery with axillary LN evaluation for clinically node-negative T1-T2 breast cancer. Three radiologists blinded to the axillary surgery results independently reviewed the US images. Tumor distance from the skin and distance from the nipple were determined based on the US report. Association between US features of a breast tumor and axillary LN metastasis was assessed using a multivariate logistic regression model after controlling for clinicopathologic variables. Results Of the 138 patients, 28 (20.3%) had nodal metastasis. At univariate analysis, tumor distance from the skin ( P = 0.019), tumor size on US ( P = 0.023), calcifications ( P = 0.036), architectural distortion ( P = 0.001), and lymphovascular invasion ( P = 0.049) were associated with axillary LN metastasis. At multivariate analysis, shorter skin-to-tumor distance (odds ratio [OR] = 4.15; 95% confidence interval [CI] = 1.01-16.19; P = 0.040) and masses with associated architectural distortion (OR = 3.80; 95% CI = 1.57-9.19; P = 0.003) were independent predictors of axillary LN metastasis. Conclusion US features of breast cancer can be promising factors associated with axillary LN metastasis in patients with clinically node-negative early-stage breast cancer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, H; Cape Breton Cancer Centre, Sydney, NS

Purpose: To perform the comparison of dose distributions and dosevolume- histograms generated by VMAT and conventional field-in-field technique for left-sided breast and chestwall cancers; to determine whether VMAT offers more dosimetric benefits than does the field-in-field technique. Methods: All VMAT and field-in-filed plans were produced in Eclipse(version 10). Five plans were generated for left-sided breast and leftsided chestwall with supraclavicular nodes, respectively. A clockwise arc (CW) and a counter-clockwise arc (CCW) were used with start and stop angles being 310o±10o and 140o±10o. Collimator angles were 30o for CW and 330o for CCW. The conformity index (CI) is the ratio ofmore » V95% over PTV. The homogeneity index (HI) is the ratio of the difference between D2% and D98% over the prescribed dose. The V5, as an indicator of low dose bath to organs-at-risk, was used for ipsilateral lung, heart, contralateral lung, and contralateral breast. The V20, as an indicator of radiation pneumonitis, was used for ipsilateral lung. Results: Breast/chestwall VMAT delivers much higher low dose bath to ipsilateral lung, contralateral lung and contralateral breast/chestwall for both intact breast and chestwall with nodes. V5 for heart is increased in VMAT plans. V20 for ipsilateral lung is lower in VMAT plans. PTV coverage is similar for both techniques. For one particular chestwall patient with supraclavicular and internal mammary nodes, VMAT offers superior dose coverage of PTVs with slightly more low-dose-wash to heart, contralateral lung and contralateral breast. Conclusion: This study indicates that there is generally no benefit using VMAT for left-sided intact breast, due to large low-dose-bath (5Gy) to normal tissues with insignificant improvement in PTV coverage. Dosimetric benefits will be seen in VMAT plans for some chestwall patients with large size, and/or internal mammary nodes, etc. Whether a chestwall patient is treated with VMAT should be carefully analyzed on an individual basis.« less

Progranulin expression in breast cancer with different intrinsic subtypes.

PubMed

Li, Li Qin; Min, Li Shan; Jiang, Qun; Ping, Jin Liang; Li, Jing; Dai, Li Cheng

2012-04-15

Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. We found that high progranulin expression was associated with higher breast carcinoma angiogenesis, reflected by increased vascular endothelial growth factor expression and higher microvessel density. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathological features in different intrinsic subtypes of breast carcinoma biopsies. The aim of this study was to investigate the progranulin expression profiles in the intrinsic subtypes of breast carcinomas and their relevance to histopathological and clinicopathological features. Tissue blocks containing 264 cases of breast carcinomas from 2006 to 2009 were classified as different intrinsic subtypes. Tissues of four intrinsic subtypes were immunostained for progranulin, vascular endothelial growth factor and CD105. Their relevance to histopathological and clinicopathological features was also analyzed. Twenty tissue samples from breast fibroadenomas were included in this study. Progranulin expression showed no significant differences in different intrinsic subtypes, although an increasing tendency could be found in the triple-negative breast cancer (TNBC) subgroup (χ(2)=5.00, df=3, p=0.17). However, differences were significant when pathologically node metastasis-positive (pN(+)) TNBC were excluded (χ(2)=17.84, df=3, p<0.01). Some clinicopathological parameters, including CK5/6 (χ(2)=0.08, df=3, p=0.78), E-cadherin (χ(2)=0.71, df=3, p=0.40) and P53 (χ(2)=0.05, df=3, p=0.83), displayed no correlation with activity of progranulin in pathologically node metastasis-negative (pN(-)) TNBC. It was noted that the EGFR expression level of the pN(-) TNBC subtype was significantly higher in cases with strong progranulin expression than in cases with weak progranulin expression (χ(2)=11.26, df=1, p<0.01). A significantly higher expression level of progranulin in pN(-) TNBC suggests that progranulin is a promising new target for pN(-) TNBC treatment. Strong expression of progranulin correlates with positive EGFR expression in the pN(-) TNBC subtype. The close relationship between EGFR and progranulin/VEGF/CD105 expression may partly play a role in high angiogenesis levels in the pN(-) TNBC subtype. Copyright © 2012 Elsevier GmbH. All rights reserved.

Increased Detection of Lymphatic Vessel Invasion by D2-40 (Podoplanin) in Early Breast Cancer: Possible Influence on Patient Selection for Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Debald, Manuel, E-mail: debald@uni-bonn.d; Poelcher, Martin; Flucke, Uta

2010-07-15

Purpose: Several international trials are currently investigating accelerated partial breast irradiation (APBI) for patients with early-stage breast cancer. According to existing guidelines, patients with lymphatic vessel invasion (LVI) do not qualify for APBI. D2-40 (podoplanin) significantly increases the frequency of LVI detection compared with conventional hematoxylin and eosin (HE) staining in early-stage breast cancer. Our purpose was to retrospectively assess the hypothetical change in management from APBI to whole breast radiotherapy with the application of D2-40. Patients and Methods: Immunostaining with D2-40 was performed on 254 invasive breast tumors of 247 patients. The following criteria were used to determine themore » eligibility for APBI: invasive ductal adenocarcinoma of {<=}3 cm, negative axillary node status (N0), and unifocal disease. Of the 247 patients, 74 with available information concerning LVI, as detected by D2-40 immunostaining and routine HE staining, formed our study population. Results: Using D2-40, our results demonstrated a significantly greater detection rate (p = .031) of LVI compared with routine HE staining. LVI was correctly identified by D2-40 (D2-40-positive LVI) in 10 (13.5%) of 74 tumors. On routine HE staining, 4 tumors (5.4%) were classified as HE-positive LVI. Doublestaining of these specimens with D2-40 unmasked false-positive LVI status in 2 (50%) of the 4 tumors. According to the current recommendations for APBI, immunostaining with D2-40 would have changed the clinical management from APBI to whole breast radiotherapy in 8 (10.8%) of 74 patients and from whole breast radiotherapy to APBI in 2 patients (2.7%). Conclusion: These data support the implementation of D2-40 immunostaining in the routine workup to determine a patient's eligibility for APBI.« less

[A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].

PubMed

Hayashi, Keiko; Enomoto, Takumo; Oshida, Sayuri; Habiro, Takeyoshi; Hatate, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

2013-11-01

We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

Effect of Occult Metastases on Survival in Node-Negative Breast Cancer

PubMed Central

Weaver, Donald L.; Ashikaga, Takamaru; Krag, David N.; Skelly, Joan M.; Anderson, Stewart J.; Harlow, Seth P.; Julian, Thomas B.; Mamounas, Eleftherios P.; Wolmark, Norman

2011-01-01

BACKGROUND Retrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking. METHODS We randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimension. RESULTS Occult metastases were detected in 15.9% (95% confidence interval [CI], 14.7 to 17.1) of 3887 patients. Log-rank tests indicated a significant difference between patients in whom occult metastases were detected and those in whom no occult metastases were detected with respect to overall survival (P = 0.03), disease-free survival (P = 0.02), and distant-disease–free interval (P = 0.04). The corresponding adjusted hazard ratios for death, any outcome event, and distant disease were 1.40 (95% CI, 1.05 to 1.86), 1.31 (95% CI, 1.07 to 1.60), and 1.30 (95% CI, 1.02 to 1.66), respectively. Five-year Kaplan-Meier estimates of overall survival among patients in whom occult metastases were detected and those without detectable metastases were 94.6% and 95.8%, respectively. CONCLUSIONS Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points). These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003830.) PMID:21247310

Strain elastography of abnormal axillary nodes in breast cancer patients does not improve diagnostic accuracy compared with conventional ultrasound alone.

PubMed

Park, Young Mi; Fornage, Bruno D; Benveniste, Ana Paula; Fox, Patricia S; Bassett, Roland L; Yang, Wei Tse

2014-12-01

The purpose of this study was to determine the diagnostic value of strain elastography (SE) alone and in combination with gray-scale ultrasound in the diagnosis of benign versus metastatic disease for abnormal axillary lymph nodes in breast cancer patients. Patients with breast cancer and axillary lymph nodes suspicious for metastatic disease on conventional ultrasound who underwent SE of the suspicious node before ultrasound-guided fine-needle aspiration biopsy (FNAB) were included in this study. On conventional ultrasound, the long- and short-axis diameters, long-axis-to-short-axis ratio, cortical echogenicity, thickness, and evenness were documented. The nodal vascularity was assessed on power Doppler imaging. Elastograms were evaluated for the percentage of black (hard) areas in the lymph node, and the SE-ultrasound size ratio was calculated. Two readers assessed the images independently and then in consensus in cases of disagreement. ROC AUCs were calculated for conventional ultrasound, SE, and both methods combined. Interreader reliability was assessed using kappa statistics. A total of 101 patients with 104 nodes were examined; 35 nodes were benign, and 69 had metastases. SE alone showed a significantly lower AUC (62%) than did conventional ultrasound (92%) (p<0.001). There was no difference between the AUC of conventional ultrasound and the AUC of the combination of conventional ultrasound and SE (93%) (p=0.16). Interreader reliability was moderate for all variables (κ≥0.60) except the SE-ultrasound size ratio (κ=0.35). Added SE does not improve the diagnostic ability of conventional ultrasound when evaluating abnormal axillary lymph nodes.

Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium.

PubMed

Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet; Platte, Radka; Hopper, John L; Southey, Melissa C; Apicella, Carmel; Hammet, Fleur; Schmidt, Marjanka K; Broeks, Annegien; Tollenaar, Rob A E M; Van't Veer, Laura J; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Strick, Reiner; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Burwinkel, Barbara; Marme, Federik; Schneeweiss, Andreas; Sohn, Christof; Bojesen, Stig; Flyger, Henrik; Nordestgaard, Børge G; Benítez, Javier; Milne, Roger L; Ignacio Arias, Jose; Zamora, M Pilar; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Rahman, Nazneen; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Chang-Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuri I; Karstens, Johann Hinrich; Bermisheva, Marina; Prokofieva, Darya; Gantcev, Shamil Hanafievich; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Mannermaa, Arto; Kosma, Veli-Matti; Soini, Ylermi; Kataja, Vesa; Lambrechts, Diether; Yesilyurt, Betül T; Chrisiaens, Marie-Rose; Peeters, Stephanie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus; Lee, Adam M; Diasio, Robert; Wang, Xianshu; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Maclean, Catriona; Offit, Ken; Robson, Mark; Joseph, Vijai; Gaudet, Mia; John, Esther M; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Brinton, Louise A; Sherman, Mark E; Lissowska, Jolanta; Chanock, Stephen J; Hooning, Maartje; Martens, John W M; van den Ouweland, Ans M W; Collée, J Margriet; Hall, Per; Czene, Kamila; Cox, Angela; Brock, Ian W; Reed, Malcolm W R; Cross, Simon S; Pharoah, Paul; Dunning, Alison M; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Shen, Chen-Yang; Ding, Shian-ling; Hsu, Huan-Ming; Yu, Jyh-Cherng; Anton-Culver, Hoda; Ziogas, Argyrios; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Orr, Nick; Trentham-Dietz, Amy; Egan, Kathleen; Newcomb, Polly; Titus-Ernstoff, Linda; Easton, Doug; Spurdle, Amanda B

2011-12-01

A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI = 1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI = 0.98-1.07, case-only P-heterogeneity = 7.6 × 10(-5)]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer.

Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium†

PubMed Central

Figueroa, Jonine D.; Garcia-Closas, Montserrat; Humphreys, Manjeet; Platte, Radka; Hopper, John L.; Southey, Melissa C.; Apicella, Carmel; Hammet, Fleur; Schmidt, Marjanka K.; Broeks, Annegien; Tollenaar, Rob A.E.M.; Van't Veer, Laura J.; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Strick, Reiner; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Burwinkel, Barbara; Marme, Federik; Schneeweiss, Andreas; Sohn, Christof; Bojesen, Stig; Flyger, Henrik; Nordestgaard, Børge G.; Benítez, Javier; Milne, Roger L.; Ignacio Arias, Jose; Zamora, M. Pilar; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Rahman, Nazneen; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Chang-Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuri I.; Karstens, Johann Hinrich; Bermisheva, Marina; Prokofieva, Darya; Hanafievich Gantcev, Shamil; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Mannermaa, Arto; Kosma, Veli-Matti; Soini, Ylermi; Kataja, Vesa; Lambrechts, Diether; Yesilyurt, Betül T.; Chrisiaens, Marie-Rose; Peeters, Stephanie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus; Lee, Adam M.; Diasio, Robert; Wang, Xianshu; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Maclean, Catriona; Offit, Ken; Robson, Mark; Joseph, Vijai; Gaudet, Mia; John, Esther M.; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene; Knight, Julia A.; Marie Mulligan, Anna; O'Malley, Frances P.; Brinton, Louise A.; Sherman, Mark E.; Lissowska, Jolanta; Chanock, Stephen J.; Hooning, Maartje; Martens, John W.M.; van den Ouweland, Ans M.W.; Collée, J. Margriet; Hall, Per; Czene, Kamila; Cox, Angela; Brock, Ian W.; Reed, Malcolm W.R.; Cross, Simon S.; Pharoah, Paul; Dunning, Alison M.; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Shen, Chen-Yang; Ding, Shian-ling; Hsu, Huan-Ming; Yu, Jyh-Cherng; Anton-Culver, Hoda; Ziogas, Argyrios; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Orr, Nick; Trentham-Dietz, Amy; Egan, Kathleen; Newcomb, Polly; Titus-Ernstoff, Linda; Easton, Doug; Spurdle, Amanda B.

2011-01-01

A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r2= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI = 1.10–1.16 and, for ER-negative tumors, OR was 1.03, 95% CI = 0.98–1.07, case-only P-heterogeneity = 7.6 × 10−5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P= 6.7 × 10−3) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. PMID:21852249

First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 cases.

PubMed

Elidrissi Errahhali, Manal; Elidrissi Errahhali, Mounia; Ouarzane, Meryem; El Harroudi, Tijani; Afqir, Said; Bellaoui, Mohammed

2017-01-09

Breast cancer is the most frequent malignancy among women in Eastern Morocco. In this paper, we provide the first report on molecular breast cancer subtypes in this region. This is the largest population-based study on breast cancer among Moroccan women. We analyzed 2260 breast cancer cases diagnosed at the Hassan II Regional Oncology Center between October 2005 and December 2012. Clinico-pathological and therapeutic features were studied. Molecular subtypes were determined and their associations with the clinico-pathological characteristics of the tumors were examined. The mean age at diagnosis was 48.7 years ±11.4. Invasive ductal carcinoma was the predominant histological type (77.1%), followed by lobular invasive carcinoma (15.3%). The mean size of breast tumors was 3.5 cm ± 1.96, and 84% of our patients are diagnosed with tumors of more than 2 cm. Histological grade II tumors were the most frequent (70.4%), followed by advanced histological grade (18%). Lymph node positive tumors were observed in 64.8% of cases and 29.3% of patients had distant metastasis. Most tumors were hormone receptor-positive (73%) and 28.6% were HER2 positive. 86.1% of patients with hormone receptor-positive breast cancer were given hormone therapy, while 68.9% of patients with HER2+ breast cancer received targeted therapy with Herceptin. Luminal A was the commonest molecular subtype, followed by Luminal B, Triple Negative and HER2. The highest prevalence of premenopausal patients was observed in Triple Negative subtype (72.2%), followed by HER2 (64.1%), Luminal B (62.2%), and Luminal A (55.1%). Luminal B subtype had a poorer prognosis than Luminal A. Compared with Triple Negative, HER2 subtype tend to spread more aggressively and is associated with poorer prognosis. Unlike Western countries, breast cancer occurs at an earlier age and is diagnosed at a more advanced stage in Eastern Morocco. In this region, hormone receptor-positive tumors are predominant and so the majority of breast cancer patients should benefit from hormone therapy. HER2 subtype presents an aggressive tendency, suggesting the importance of anti-HER2 therapy. This study will contribute in developing appropriate screening and cancer management strategies in Eastern Morocco.

The predictive value of methylene blue dye as a single technique in breast cancer sentinel node biopsy: a study from Dharmais Cancer Hospital.

PubMed

Brahma, Bayu; Putri, Rizky Ifandriani; Karsono, Ramadhan; Andinata, Bob; Gautama, Walta; Sari, Lenny; Haryono, Samuel J

2017-02-07

Axillary lymph node dissection (ALND) has been the standard treatment of breast cancer axillary staging in Indonesia. The limited facilities of radioisotope tracer and isosulfan or patent blue dye (PBD) have been the major obstacles to perform sentinel node biopsy (SNB) in our country. We studied the application of 1% methylene blue dye (MBD) alone for SNB to overcome the problem. This prospective study enrolled 108 patients with suspicious malignant lesions or breast cancer stages I-III. SNB was performed using 2-5 cc of 1% MBD and proceeded with ALND. The histopathology results of sentinel nodes (SNs) were compared with axillary lymph nodes (ALNs) for diagnostic value assessments. There were 96 patients with invasive carcinoma from July 2012 to September 2014 who were included in the final analysis. The median age was 50 (25-69) years, and the median pathological tumor size was 3 cm (1-10). Identification rate of SNs was 91.7%, and the median number of the identified SNs was 2 (1-8). Sentinel node metastasis was found in 53.4% cases and 89.4% of them were macrometastases. The negative predictive value (NPV) of SNs to predict axillary metastasis was 90% (95% CI, 81-99%). There were no anaphylactic reactions, but we found 2 cases with skin necrosis. The application of 1% MBD as a single technique in breast cancer SNB has favorable identification rates and predictive values. It can be used for axillary staging, but nevertheless the technique should be applied with attention to the tumor size and grade to avoid false negative results.

Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, X. Sharon, E-mail: xqi@mednet.ucla.edu; Liu, Tian X.; Liu, Arthur K.

2014-10-01

The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for breast cancer radiotherapy. During treatment planning, not only the coverage of the planning target volume (PTV) but also the minimization of the dose to critical structures, such as the lung, heart, and contralateral breast tissue, need to be considered. Because of the complexity and variations of patient anatomy, more advanced radiotherapy techniques are sometimes desired to better meet the planning goals. In this study, we evaluated external-beam radiation treatment techniques for left breast cancer using various delivery platforms: fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy (sIMRT), and rotational radiotherapy includingmore » Elekta volumetric-modulated arc therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left-sided breast cancer who did or did not have positive lymph nodes and were previously treated with 3DCRT/sIMRT to the entire breast were selected, their treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and target minimum/maximum/mean doses were evaluated. It is found that for plans providing comparable PTV coverage, the Elekta VMAT plans were generally more inhomogeneous than the TH and TD plans. For the cases with regional node involvement, the average mean doses administered to the heart were 9.2 (± 5.2) and 8.8 (± 3.0) Gy in the VMAT and TH plans compared with 11.9 (± 6.4) and 11.8 (± 9.2) Gy for the 3DCRT and TD plans, respectively, with slightly higher doses given to the contralateral lung or breast or both. On average, the total monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT plans for advanced breast cancer requiring regional nodal treatment. However, for early-stage breast cancer fixed-field radiotherapy is potentially more beneficial in terms of OAR sparing.« less

Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy.

PubMed

Qi, X Sharon; Liu, Tian X; Liu, Arthur K; Newman, Francis; Rabinovitch, Rachel; Kavanagh, Brian; Hu, Y Angie

2014-01-01

The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for breast cancer radiotherapy. During treatment planning, not only the coverage of the planning target volume (PTV) but also the minimization of the dose to critical structures, such as the lung, heart, and contralateral breast tissue, need to be considered. Because of the complexity and variations of patient anatomy, more advanced radiotherapy techniques are sometimes desired to better meet the planning goals. In this study, we evaluated external-beam radiation treatment techniques for left breast cancer using various delivery platforms: fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy (sIMRT), and rotational radiotherapy including Elekta volumetric-modulated arc therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left-sided breast cancer who did or did not have positive lymph nodes and were previously treated with 3DCRT/sIMRT to the entire breast were selected, their treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and target minimum/maximum/mean doses were evaluated. It is found that for plans providing comparable PTV coverage, the Elekta VMAT plans were generally more inhomogeneous than the TH and TD plans. For the cases with regional node involvement, the average mean doses administered to the heart were 9.2 (± 5.2) and 8.8 (± 3.0)Gy in the VMAT and TH plans compared with 11.9 (± 6.4) and 11.8 (± 9.2)Gy for the 3DCRT and TD plans, respectively, with slightly higher doses given to the contralateral lung or breast or both. On average, the total monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT plans for advanced breast cancer requiring regional nodal treatment. However, for early-stage breast cancer fixed-field radiotherapy is potentially more beneficial in terms of OAR sparing. Copyright © 2014 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.