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.

Infrequent Loss of Luminal Differentiation in Ductal Breast Cancer Metastasis

PubMed Central

Calvo, Julia; Sánchez-Cid, Lourdes; Muñoz, Montserrat; Lozano, Juan José; Thomson, Timothy M.; Fernández, Pedro L.

2013-01-01

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. PMID:24205108

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.

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.

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.

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.

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 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.

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

Ultrasound-Guided Fine-Needle Aspiration of Non-palpable and Suspicious Axillary Lymph Nodes with Subsequent Removal after Tattooing: False-Negative Results and Concordance with Sentinel Lymph Nodes.

PubMed

Kim, Won Hwa; Kim, Hye Jung; Jung, Jin Hyang; Park, Ho Yong; Lee, Jeeyeon; Kim, Wan Wook; Park, Ji Young; Cheon, Hyejin; Lee, So Mi; Cho, Seung Hyun; Shin, Kyung Min; Kim, Gab Chul

2017-11-01

Ultrasonography-guided fine-needle aspiration (US-guided FNA) for axillary lymph nodes (ALNs) is currently used with various techniques for the initial staging of breast cancer and tagging of ALNs. With the implementation of the tattooing of biopsied ALNs, the rate of false-negative results of US-guided FNA for non-palpable and suspicious ALNs and concordance with sentinel lymph nodes were determined by node-to node analyses. A total of 61 patients with breast cancer had negative results for metastasis on US-guided FNA of their non-palpable and suspicious ALNs. The biopsied ALNs were tattooed with an injection of 1-3 mL Charcotrace (Phebra, Lane Cove West, Australia) ink and removed during sentinel lymph node biopsy or axillary dissection. We determined the rate of false-negative results and concordance with the sentinel lymph nodes by a retrospective review of surgical and pathologic findings. The association of false-negative results with clinical and imaging factors was evaluated using logistic regression. Of the 61 ALNs with negative results for US-guided FNA, 13 (21%) had metastases on final pathology. In 56 of 61 ALNs (92%), tattooed ALNs corresponded to the sentinel lymph nodes. Among the 5 patients (8%) without correspondence, 1 patient (2%) had 2 metastatic ALNs of 1 tattooed node and 1 sentinel lymph node. In multivariate analysis, atypical cells on FNA results (odds ratio = 20.7, p = 0.040) was independently associated with false-negative FNA results. False-negative ALNs after US-guided FNA occur at a rate of 21% and most of the tattooed ALNs showed concordance with sentinel lymph nodes. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by 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

Refining Post-Surgical Therapy for Women with Lymph Node-Positive Breast Cancer

Cancer.gov

In this trial, women with HER2-negative, HR-positive breast cancer and 1-3 positive lymph nodes with recurrence scores of 25 or lower will be randomized to undergo adjuvant chemotherapy before starting endocrine therapy or to begin endocrine therapy.

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

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.

Partial axillary lymph node dissection inferior to the intercostobrachial nerves complements sentinel node biopsy in patients with clinically node-negative breast cancer.

PubMed

Li, Jianyi; Jia, Shi; Zhang, Wenhai; Qiu, Fang; Zhang, Yang; Gu, Xi; Xue, Jinqi

2015-06-30

The practice of breast cancer diagnosis and treatment in China varies to that in western developed countries. With the unavailability of radioactive tracer technique for sentinel lymph nodes biopsy (SLNB), using blue dye alone has been the only option in China. Also, the diagnosis of breast malignant tumor in most Chinese centres heavily relies on intraoperative instant frozen histology which is normally followed by sentinel lymph nodes mapping, SLNB and the potential breast and axillary operations in one consecutive session. This practice appears to cause a high false negative rate (FNR) for SLNB. The present study aimed to investigate the impact of the current practice in China on the accuracy of SLNB, and whether partial axillary lymph node dissection (PALND), dissection of lymph nodes inferior to the intercostobrachial nerve (ICBN), was a good complementary procedure following SLNB using blue dye. 289 patients with clinically node-negative breast cancer were identified and recruited. Tumorectomy, intraoperative instant frozen histological diagnosis, SLNB using methylene blue dye, and PALND or complete axillary node dissection (ALND) were performed in one consecutive operative session. The choice of SLNB only, SLNB followed by PALND or by ALND was based on the pre-determined protocol and preoperative choice by the patient. Clinical parameters were analyzed and survival analysis was performed. 37% patients with clinically negative nodes were found nodes positive. 59 patients with positive SLN underwent ALND, including 47 patients with up to two positive nodes which were all located inferior to the ICBN. 9 patients had failed SLNB and underwent PALND. Among them, 3 (33.3%) patients were found to have one metastatic node. 149 patients showed negative SLNB but chose PALND. Among them, 30 (20.1%), 14 (9.4) and 1 (0.7%) patients were found to have one, two and three metastatic node(s), respectively. PALND detected 48 (30.4%) patients who had either failed SLNB or negative SLNB to have additional positive nodes. All the patients with up to two positive nodes had their nodes located inferior to the ICBN. The FNR of SLNB was 43%. The accuracy rate was 58%. The follow-up ranged 12-33 months. The incidence of lymphedema for SLNB, PALND, and ALND was 0%, 0%, and 25.4%, respectively (P < 0.005). The disease-free survivals for SLNB, PALND, and ALND groups were 95.8%, 96.8%, and 94.9%, respectively (p > 0.05). Under the circumstances of current practice in China, PALND is a good complementary procedure following SLNB in clinically node-negative breast cancer.

[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.

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.

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.

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.

[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.

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.

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.

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.

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.

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

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.

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

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

[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.

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.

Nomogram for prediction of level 2 axillary lymph node metastasis in proven level 1 node-positive breast cancer patients.

PubMed

Jiang, Yanlin; Xu, Hong; Zhang, Hao; Ou, Xunyan; Xu, Zhen; Ai, Liping; Sun, Lisha; Liu, Caigang

2017-09-22

The current management of the axilla in level 1 node-positive breast cancer patients is axillary lymph node dissection regardless of the status of the level 2 axillary lymph nodes. The goal of this study was to develop a nomogram predicting the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in patients with level 1 axillary node-positive breast cancer. We reviewed the records of 974 patients with pathology-confirmed level 1 node-positive breast cancer between 2010 and 2014 at the Liaoning Cancer Hospital and Institute. The patients were randomized 1:1 and divided into a modeling group and a validation group. Clinical and pathological features of the patients were assessed with uni- and multivariate logistic regression. A nomogram based on independent predictors for the L-2-ALNM identified by multivariate logistic regression was constructed. Independent predictors of L-2-ALNM by the multivariate logistic regression analysis included tumor size, Ki-67 status, histological grade, and number of positive level 1 axillary lymph nodes. The areas under the receiver operating characteristic curve of the modeling set and the validation set were 0.828 and 0.816, respectively. The false-negative rates of the L-2-ALNM nomogram were 1.82% and 7.41% for the predicted probability cut-off points of < 6% and < 10%, respectively, when applied to the validation group. Our nomogram could help predict L-2-ALNM in patients with level 1 axillary lymph node metastasis. Patients with a low probability of L-2-ALNM could be spared level 2 axillary lymph node dissection, thereby reducing postoperative morbidity.

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.

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

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.

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.

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

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

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.

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

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer.

PubMed

Andreis, D; Bonardi, S; Allevi, G; Aguggini, S; Gussago, F; Milani, M; Strina, C; Spada, D; Ferrero, G; Ungari, M; Rocca, A; Nanni, O; Roviello, G; Berruti, A; Harris, A L; Fox, S B; Roviello, F; Polom, K; Bottini, A; Generali, D

2016-10-01

Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%). Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered. Copyright © 2016 Elsevier Ltd. All rights reserved.

Axillary Lymph Node Evaluation Utilizing Convolutional Neural Networks Using MRI Dataset.

PubMed

Ha, Richard; Chang, Peter; Karcich, Jenika; Mutasa, Simukayi; Fardanesh, Reza; Wynn, Ralph T; Liu, Michael Z; Jambawalikar, Sachin

2018-04-25

The aim of this study is to evaluate the role of convolutional neural network (CNN) in predicting axillary lymph node metastasis, using a breast MRI dataset. An institutional review board (IRB)-approved retrospective review of our database from 1/2013 to 6/2016 identified 275 axillary lymph nodes for this study. Biopsy-proven 133 metastatic axillary lymph nodes and 142 negative control lymph nodes were identified based on benign biopsies (100) and from healthy MRI screening patients (42) with at least 3 years of negative follow-up. For each breast MRI, axillary lymph node was identified on first T1 post contrast dynamic images and underwent 3D segmentation using an open source software platform 3D Slicer. A 32 × 32 patch was then extracted from the center slice of the segmented tumor data. A CNN was designed for lymph node prediction based on each of these cropped images. The CNN consisted of seven convolutional layers and max-pooling layers with 50% dropout applied in the linear layer. In addition, data augmentation and L2 regularization were performed to limit overfitting. Training was implemented using the Adam optimizer, an algorithm for first-order gradient-based optimization of stochastic objective functions, based on adaptive estimates of lower-order moments. Code for this study was written in Python using the TensorFlow module (1.0.0). Experiments and CNN training were done on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. Two class axillary lymph node metastasis prediction models were evaluated. For each lymph node, a final softmax score threshold of 0.5 was used for classification. Based on this, CNN achieved a mean five-fold cross-validation accuracy of 84.3%. It is feasible for current deep CNN architectures to be trained to predict likelihood of axillary lymph node metastasis. Larger dataset will likely improve our prediction model and can potentially be a non-invasive alternative to core needle biopsy and even sentinel lymph node evaluation.

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.

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

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.

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.

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.

Expression and clinical significance of matrix metalloproteinase-9 in lymphatic invasiveness and metastasis of breast cancer.

PubMed

Wu, Qiu-Wan; Yang, Qing-Mo; Huang, Yu-Fan; She, Hong-Qiang; Liang, Jing; Yang, Qiao-Lu; Zhang, Zhi-Ming

2014-01-01

Matrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear. MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated. MMP-9(+) staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05). MMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.

[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.

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.

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

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.

miR-205 and miR-200c: Predictive Micro RNAs for Lymph Node Metastasis in Triple Negative Breast Cancer

PubMed Central

Yilmaz, Ismail; Narli, Gizem; Haholu, Aptullah; Kucukodaci, Zafer; Demirel, Dilaver

2014-01-01

Purpose We examined expression profiles of 16 micro RNAs (miRNAs) in triple negative breast cancers to identify their potential as biomarkers for lymph node metastasis. Methods The expression profiles of miR-9, miR-21, miR-30a, miR-30d, miR-31, miR-34a, miR-34c, miR-100, miR-122, miR-125b, miR-146a, miR-146b, miR-155, miR-181a, miR-200c, and miR-205 were examined by using real-time quantitative reverse transcription polymerase chain reaction in tumor samples and corresponding benign breast tissues. Their associations with histopathological features and prognostic parameters were assessed. Results When compared with the expression in benign breast tissues, seven of the miRNAs (miR-31, miR-205, miR-34a, miR-146a, miR-125b, miR-34c, and miR-181a) were downregulated more than 1.5-fold in tumor tissues, whereas, only miR-21 was found to be upregulated more than 1.5-fold in tumor tissues. Although miR-200c levels were decreased only 1.12-fold in tumor tissues, the reduced expressions of miR-200c and miR-205 were significantly associated with lymph node metastasis (p=0.021 and p=0.016, respectively). Conclusion Our results demonstrate that miR-205 and miR-200c expression levels may be useful in predicting lymph node metastasis in triple negative breast cancer patients. PMID:25013435

[The Role of Supraclavicular lymph node dissection in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis].

PubMed

Zhang, W; Qi, X M; Chen, A X; Zhang, P; Cao, X C; Xiao, C H

2017-05-23

Objective: In this study, we evaluated the effect of supraclavicular lymph node dissection in breast cancer patients who presented with ipsilateral supraclavicular lymph node metastasis (ISLM) without distant metastasis. Methods: A total of 90 patients with synchronous ISLM without distant metastasis between 2000 and 2009 were retrospectively analyzed. Patients were retrospectively divided into two groups, namely supraclavicular lymph node dissection group(34 patients) and non-dissection group(56 patients), according to whether they underwentsupraclavicular lymph node dissection or not.The Kaplan-Meier method was applied to analyze the locoregional relapse free survival (LRFS) and overall survival(OS). Results: Median follow-upwas 85 months(range, 6 to 11 months). Local recurrence in 32 cases, 47 cases of distant metastasis, of which 25 patients were accompanied by both locoregional relapse and distant metastasis. Of the 32 patients with locoregional relapse, 11 patients were in the lymph node dissection group and 21 patients in the control group. Of the 47 patients with distant metastases, 17 were treated with lymph node dissection, 30 in the control group. Thirty-two patients died in the whole group and 16 patients underwentlymph node dissection and 16 patients didn't. There was no significant difference between the rate of 5-year LRFS and 5-year OS ( P =0.359, P =0.246). For patients of ER negative, the 5-year loco-regional relapse free survival rates were 63.7% and 43.3% in supraclavicular lymph node dissection group and control group, respectively. The 5-year overall survival rates were 52.1% and 52.3%, respectively, and there were no statistically significant differences ( P =0.118, P =0.951). For patients of PR negative, the 5-yearloco-regional relapse free rates were 59.8% and 46.2%, respectively, and the 5-year overall survival rates were 50.6% and 43.2%, respectively, and there was no significant difference between the two groups ( P =0.317, P =0.973). The 5-year recurrence-free survival rates of human epidermal growth factor receptor 2 (HER2)-positive patients were 61.2% and 48.0%( P =0.634), respectively, and the 5-year overall survival rates were 37.2% and 65.4%( P =0.032). Forty-seven patients suffered distant metastases and the 5-year metastases free survival rates were 37.3% and 38.5% in supraclavicular lymph node dissection group and control group, respectively. Conclusion: Supraclavicular lymph node dissection maybe an effective approach to improve the loco-regional control for the patients with ISLM, especially for ER negative and PR negative subtypes, but it might has adverseeffects for the patients with negative HER2 status.

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.

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.

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

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.

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

[Risk factors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node ≤ 2].

PubMed

Gao, Yajun; He, Yingjian; Fan, Zhaoqing; Ouyang, Tao

2014-08-13

To explore retrospectively the risk factors of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with sentinel lymph node metastasis ≤ 2 and examine the likelihood of non-sentinel lymph node prediction. A sentinel lymph node biopsy database containing 455 breast cancer patients admitted between July 2005 and February 2012 at Beijing Cancer Hospital was analyzed retrospectively. The patients had ≤ 2 positive sentinel lymph node and complete axillary lymph node dissection. The SLNS⁺/SLNS ratio (P = 0.001), histological grade (P = 0.075), size of mass (P = 0.023) and onset age (P = 0.074) were correlated with NSLN metastases. Only SLNS⁺/SLNS (OR 0.502 95% CI 0.322-0.7844) , histological grade ratio (histological grade ratio II, III and others vs grade I OR 2.696, 2.102, 3.662) were significant independent predictors for NSLN metastases . The ROC value was 0.62 (0.56, 0.68). For ≤ 2 positive sentinel lymph nodes of breast cancer, ratio of SLNS⁺/SLNS and histological grading are independent factors affecting NSLN metastases. However, the results remain unsatisfactory for predicting the status of NSLN.

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

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

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.

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.

Poor Prognosis of Lower Inner Quadrant in Lymph Node-negative Breast Cancer Patients Who Received No Chemotherapy: A Study Based on Nationwide Korean Breast Cancer Registry Database.

PubMed

Hwang, Ki-Tae; Kim, Jongjin; Kim, Eun-Kyu; Jung, Sung Hoo; Sohn, Guiyun; Kim, Seung Il; Jeong, Joon; Lee, Hyouk Jin; Park, Jin Hyun; Oh, Sohee

2017-07-01

We aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer. Data of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer-specific survival (BCSS) according to primary tumor site. Central portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P < .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P < .001) and 1.215 (95% CI, 1.097-1.345, P < .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P < .001). For lymph node-negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P < .001), but that effect disappeared in the subgroup with chemotherapy (P = .058). LIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node-negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

German, Austrian and Swiss consensus conference on the diagnosis and local treatment of the axilla in breast cancer.

PubMed

Hoffmann, Jürgen; Souchon, Rainer; Lebeau, Annette; Öhlschlegel, Christian; Gruber, Günther; Rageth, Christoph; Weber, Walter; Harbeck, Nadia; Janni, Wolfgang; Kreipe, Hans; Fitzal, Florian; Resch, Alexandra; Bago-Horvath, Zsuzsanna; Peintinger, Florentia

2013-07-01

The German, Austrian and Swiss (D.A.CH) Societies of Senology gathered together in 2012 to address dwelling questions regarding axillary clearance in breast cancer patients. The Consensus Panel consisted of 14 members of these societies and included surgical oncologists, gynaecologists, pathologists and radiotherapists. With regard to omitting axillary lymph node dissection in sentinel lymph node macrometastases, the Panel consensually accepted this option for low-risk patients only. A simple majority voted against extending radiotherapy to the axilla after omitting axillary dissection in N1 disease. Consensus was yielded for the use of axillary ultrasound and prospective registers for such patients in the course of follow-up. The questions regarding neoadjuvant therapy and the timing of sentinel lymph node biopsy failed to yield consensus, yet both options (before or after) are possible in clinically node-negative disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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.

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

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.

Primary epithelioid trophoblastic tumor with a synchronous breast carcinoma detected only with FDG-PET/CT Scan.

PubMed

Kara, T; Ozcan Kara, P; Baba, F; Celik, C; Kara Gedik, G

2011-01-01

Epithelioid trophoblastic tumor is a recently described, rare and distinctive type of gestational trophoblastic tumor. We report the case of a 31-year old patient who had a full-term pregnancy 18 months before presentation. She had a right axillary lymph node metastasis and was referred for FDG-PET/CT scan for evaluation of distant metastasis and to detect primary malignancy. The axillary lymph node biopsy revealed metastatic breast carcinoma. FDG-PET/CT revealed increased uptake of right axillary lymph node, soft tissue density lesion with a diameter of 24 mm on left cervical region with increased FDG uptake, increased uptake on cervical region and left inguinal lymph node with increased uptake. Pelvic MRI imaging and ultrasonography were negative for malignancy in cervical region. Biopsy of the lesion was consistent with epithelioid trophoblastic tumor in cervical region. Gestational trophoblastic tumor was not suspected because she had no signs such as abnormal vaginal bleeding. FDG-PET/CT demonstrated the primary lesion in cervical region. We report a rare case of primary epithelioid trophoblastic tumor detected only with FDG-PET/CT scan which synchronized with breast carcinoma. Copyright © 2010 Elsevier España, S.L. and SEMNIM. All rights reserved.

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 ...

Risk of Subclinical Micrometastatic Disease in the Supraclavicular Nodal Bed According to the Anatomic Distribution in Patients With Advanced Breast Cancer

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

Reed, Valerie K.; Cavalcanti, Jose L.; Strom, Eric A.

Purpose: To determine the anatomic distribution of gross supraclavicular nodes within the supraclavicular fossa using 2-deoxy-2-[F-18] fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, and to evaluate likely coverage of specific regions of the supraclavicular fossa using standard radiation fields. Methods and Materials: We identified 33 patients with advanced or metastatic breast cancer who had a PET/CT scan demonstrating hypermetabolic supraclavicular lymph nodes in 2005. The locations of the involved lymph nodes were mapped onto a single CT set of images of the supraclavicular fossa. These lymph nodes were also mapped onto the treatment-planning CT dataset of 4 patients treatedmore » in our institution (2 patients with biopsy-proven supraclavicular nodes and 2 patients with clinically negative supraclavicular nodes). Results: We were able to determine the distribution of 52 supraclavicular lymph nodes in 32 patients. Of 32 patients, 28 (87%) had a history of metastatic disease, and 2 patients had isolated nodal recurrences. Five patients had supraclavicular nodes posterior to the vertebral body transverse process, and several lymph nodes were in close proximity to the medial field border, raising the possibility of geographic miss in these areas. Conclusions: In patients with locally advanced disease, increased coverage of the supraclavicular fossa medially and posteriorly may be warranted.« less

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.

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.

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.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update

PubMed Central

Krop, Ian; Ismaila, Nofisat; Andre, Fabrice; Bast, Robert C.; Barlow, William; Collyar, Deborah E.; Hammond, M. Elizabeth; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Wolff, Antonio C.; Stearns, Vered

2018-01-01

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor–positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki. PMID:28692382

Effect of Neoadjuvant Chemotherapy on Axillary Lymph Node Positivity and Numbers in Breast Cancer Cases.

PubMed

Uyan, Mikail; Koca, Bulent; Yuruker, Savas; Ozen, Necati

2016-01-01

The aim of this study is to compare the numbers of axillary lymph nodes (ALN) taken out by dissection between patients with breast cancer operated on after having neoadjuvant chemotherapy (NAC) treatment and otherswithout having neoadjuvant chemotherapy, and to investigate factors affecting lymph node positivity. A total of 49 patients operated due to advanced breast cancer after neoadjuvant chemotherapy and 144 patients with a similar stage of the cancer having primary surgical treatment without chemotherapy at the general surgery clinic of Ondokuz Mayis University Medicine Faculty between the dates 01.01.2006 and 31.10.2012 were included in the study. The total number of lymph nodes taken out by axillary dissection (ALND) was categorized as the number of positive lymph nodes and divided into <10 and ≥10. The variables to be compared were analysed using the program SPSS 15.0 with P<0.05 accepted as significant. Median number of dissected lymph nodes from the patient group having neoadjuvant chemotherapy was 16 (16-33) while it was 20 (5-55) without chemotherapy. The respective median numbers of positive lymph nodes were 5 ( 0-19) and 10 (0-51). In 8 out of 49 neoadjuvant chemotherapy patients (16.3%), the number of dissected lymph nodes was below 10, and it was below 10 in 17 out of 144 primary surgery patients. Differences in numbers of dissected total and positive lymph nodes between two groups were significant, but this was not the case for numbers of <10 lymph nodes. The number of dissected lymph nodes from the patients with breast cancer having neoadjuvant chemotherapy may be less than without chemotherapy. This may not always be attributed to an inadequate axillary dissection. More research to evaluate the numbers of positive lymph nodes are required in order to increase the reliability of staging in the patients with breast cancer undergoing neoadjuvant chemotherapy.

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.

Beyond the false negative rate: development of quality indicators for sentinel lymph node biopsy in breast cancer.

PubMed

Quan, May Lynn; Wells, Bryan J; McCready, David; Wright, Frances C; Fraser, Novlette; Gagliardi, Anna R

2010-02-01

Sentinel lymph node biopsy (SNLB) has been adopted as the standard method of axillary staging for women with clinically node-negative early-stage breast cancer. The false negative rate as a quality indicator is impractical given the need for a completion axillary dissection to calculate. The objective of this study was to develop practical quality indicators for SLNB using an expert consensus method and to determine if they were feasible to measure. We used a modified Delphi consensus process to develop quality indicators for SLNB. A multidisciplinary expert panel reviewed potential indicators extracted from the medical literature to select quality indicators that were relevant and measurable. Feasibility was determined by abstracting the quality indicator variables from a retrospective chart review. The expert panel prioritized 11 quality indicators as benchmarks for assessing the quality of surgical care in SNLB. Nine of the indicators were measurable at the chart or institutional level. A systematic evidence- and consensus-based approach was used to develop measurable quality indicators that could be used by practicing surgeons and administrators to evaluate performance of SLNB in breast cancer.

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

[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.

Axillary lymph node metastases in adenoid cystic carcinoma of the breast. A rare finding

PubMed Central

SPILIOPOULOS, D.; MITSOPOULOS, G.; KAPTANIS, S.; HALKIAS, C.

2015-01-01

Adenoid cystic carcinoma (ACC) of the breast is a rare malignant salivary-type neoplasm that has a good prognosis and represents less than 1% of all breast cancers. It is a triple negative carcinoma that presents as a painful mass. The mean age at the time of diagnosis is 50–60 years old. The solid variant of this type of tumour with basaloid features and presence of nodal metastases is very rare and considered to have a more aggressive clinical course. We present a case with presence of axillary lymph node metastases that was successfully treated with no evidence of recurrence one year after the diagnosis and review the literature. PMID:26712257

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.

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.

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.

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

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.

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.

Predicting Likelihood of Having Four or More Positive Nodes in Patient With Sentinel Lymph Node-Positive Breast Cancer: A Nomogram Validation Study

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

Unal, Bulent; Gur, Akif Serhat; Beriwal, Sushil

2009-11-15

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The areamore » under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.« less

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.

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

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.

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.

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

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

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...

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

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.

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.

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

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.

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.

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.

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.

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.

The appropriate number of ELNs for lymph node negative breast cancer patients underwent MRM: a population-based study.

PubMed

Chi, Huiying; Zhang, Chenyue; Wang, Haiyong; Wang, Zhehai

2017-09-12

Whether number of examed lymph nodes (ELNs) would bring survival benefit for patients with negative lymph nodes after modified radical mastectomy (MRM) is uncertain. In our study, using the Surveillance Epidemiology and End Results (SEER) database between 2004 and 2009, we screened the appropriate patients with negative lymph nodes underwent MRM. The Cox proportional hazard analysis was used to determine the effect of number of ELNs on cancer specific survival (CSS). The results showed that the number of ELNs was not an independent prognostic factor on CSS ( P = 0.940). Then the X-tile mode was used to determine the appropriate threshold for ELNs count. The results showed that 9 was the appropriate cut-off point. Next, the log-rank χ 2 test was used to analyze the CSS based on different subgroup variables. The results showed that some subgroup variables including age < 50/ ≥ 50, grade I/III, AJCC T1/T2, ER positive/negative and PR positive/negative ,demonstrated significant CSS benefits among the patients with the number of ELNs ≤ 9 (all, P < 0.05). However, three subgroup variables including grade II, AJCC T3 and AJCC T4, the patients with the number of ELNs ≤ 9 did not bring significant CSS benefits (all, P > 0.1). In conclusion, our study demonstrated that the number of ELNs was not an independent prognostic factor on CSS, and 9 can be selected as the appropriate cut-off point of ELNs for patients with negative lymph nodes who underwent MRM.

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.

Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

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

Selz, Jessica, E-mail: chaumontjessica@yahoo.fr; Stevens, Denise; Jouanneau, Ludivine

2012-12-01

Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRRmore » associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.« less

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.

Use of sentinel lymph node biopsy to select patients for local–regional therapy after neoadjuvant chemotherapy

PubMed Central

Erdahl, Lillian M.; Boughey, Judy C.

2014-01-01

Use of sentinel lymph node biopsy for axillary staging of patients with breast cancer treated with neoadjuvant chemotherapy has been widely debated. Questions arise regarding the accuracy of sentinel lymph node biopsy in axillary staging for these patients and its use to determine further local–regional therapy, including surgery and radiation therapy. For patients who are clinically node-negative at presentation, sentinel lymph node biopsy enables accurate staging of the axilla after neoadjuvant chemotherapy, and determination of which patients should go on to further axillary surgery and regional nodal radiation therapy. Importantly, performing axillary staging after completion of chemotherapy, rather than before chemotherapy, enables assessment of response to chemotherapy and the extent of residual disease. This information can assist the planning of adjuvant treatment. Recent data indicate that sentinel node biopsy can also be used to assess disease response after neoadjuvant chemotherapy for patients with clinical N1 disease at presentation. PMID:24683440

Sentinel lymph node detection in patients with early cervical cancer.

PubMed

Acharya, B C; Jihong, L

2009-01-01

Lymph node status is the most important independent prognostic factor in early stage cervical cancer. Intraoperative lymphatic mapping and sentinel lymph node detection have been increasingly evaluated in the treatment of a variety of solid tumors, particularly breast cancer and cutaneous melanoma. This study evaluated the feasibility of these procedures in patients undergoing radical hysterectomy with pelvic lymphadenectomy for early cervical cancer. A total of 30 patients with histologically diagnosed FIGO stage IA to IIA cervical cancer were enrolled to this study. They were scheduled to undergo radical abdominal hysterectomy and pelvic lymphadenectomy after injecting patent blue dye in cervix. A total of 60 SLNs (mean 2.5) were detected in 24 patients with detection rate of 80%. Bilateral SLNs were detected in 70.1% of cases. SLNs were identified in obturator and external iliac areas in 50% and 31.7%, respectively; no SLNs were discovered in the common iliac region. Seven patients (23.3%) had lymph node metastases; one of these had false negative SLN.The false negative rate and negative predictive value were 14.3% and 94.4%, respectively. SLN detection procedure with blue dye technique is a feasible procedure in cervical cancer. Patent blue dye is cheap, safe and effective tracer to detect sentinel node in carcinoma of cervix.

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.

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.

An Ultralow-Dose 1-Day Protocol With Activities Lower Than 20 MBq for the Detection of Sentinel Lymph Nodes in Breast Cancer-Experiences After 150 Cases.

PubMed

Kolberg, Hans-Christian; Afsah, Shabnam; Kuehn, Thorsten; Winzer, Ute; Akpolat-Basci, Leyla; Stephanou, Miltiades; Wetzig, Sarah; Hoffmann, Oliver; Liedtke, Cornelia

2017-01-01

Common protocols for the detection of sentinel lymph nodes in early breast cancer often include the injection of the tracer 1 day before surgery. In order to detect enough activity on the day of surgery, the applied activity in many protocols is as high as several hundred MBq. So far, very few protocols with an activity below 20 MBq have been reported. We developed an ultralow-dose 1-day protocol with a mean activity lower than 20 MBq in order to reduce radiation exposure for patients and staff. Here, we are presenting our experiences in 150 consecutive cases. A total of 150 patients with clinically and sonographically negative axilla and no multicentricity underwent a sentinel lymph node biopsy using an ultralow-dose protocol performed on the day of surgery. No patient received systemic therapy prior to sentinel node biopsy. After peritumoral injection of the tracer Technetium-99m, a lymphoscintigraphy was performed in all cases. Seven minutes before the first cut, we injected 5 mL of blue dye in the region of the areola. In 148 (98.7%) of 150 patients, at least 1 sentinel lymph node could be identified by lymphoscintigraphy; the detection rate during surgery with combined tracers Technetium-99m and blue dye was 100%. The mean applied activity was 17.8 MBq (9-20). A mean number of 1.3 (0-5) sentinel lymph nodes were identified by lymphoscintigraphy and a mean number of 1.8 (1-5) sentinel lymph nodes were removed during sentinel lymph node biopsy. Ultralow-dose 1-day protocols with an activity lower than 20 MBq are a safe alternative to 1-day or 2-day protocols with significantly higher radiation doses in primary surgery for early breast cancer. Using Technetium-99m and blue dye in a dual tracer approach, detection rates of 100% are possible in clinical routine in order to reduce radiation exposure for patients and staff.

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer.

PubMed

Inoue, Tomoo; Nishi, Toshio; Nakano, Yoshiaki; Nishimae, Ayaka; Sawai, Yuka; Yamasaki, Masaru; Inaji, Hideo

2016-03-01

There is limited information on indocyanine green (ICG) fluorescence and blue dye for detecting sentinel lymph node (SLN) in early breast cancer. A retrospective study was conducted to assess the feasibility of an SLN biopsy using the combination of ICG fluorescence and the blue dye method. Seven hundred and fourteen patients with clinically node-negative breast cancer were included in this study. They underwent SLN biopsy using a combination of ICG fluorescence and the blue dye method from March 2007 to February 2014. The ICG (a fluorescence-emitting source) and patent blue (the blue dye) were injected into the patients' subareolar region. The removed lymph nodes that had ICG fluorescence and/or blue dye uptake were defined as SLNs. The results of the SLN biopsies and follow-up results of patients who underwent SLN biopsy alone were investigated. In 711 out of 714 patients, SLNs were identified by a combination of ICG fluorescence and the blue dye method (detection rate, 99.6 %). The average number of SLNs was 2.4 (range 1-7), and the average number of resected swollen para-SLNs was 0.4 (range 0-5). Ninety-nine patients with an SLN and/or para-SLN involvement during the intraoperative pathological diagnosis underwent axillary lymph node resection (ALND). In addition, two of three patients whose SLN was not identified also underwent ALND. In 46 of 101 patients with an ALND, non-SLN involvement was not found. Follow-up results were analyzed in 464 patients with invasive carcinoma excluding those with ductal carcinoma in situ (n = 148) and those who underwent ALND (n = 101). During the follow-up period (range 4.4-87.7 months; median, 38 months), two patients (0.4 %) developed axillary lymph node recurrence. They were successfully salvaged, and to date, no further locoregional recurrence has been observed. A high rate of SLN detection and low rate of axillary lymph node recurrence were confirmed by an SLN biopsy using a combination of ICG fluorescence and the blue dye method. Therefore, it is suggested that this method may replace the combination of dye and radioisotope methods.

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.

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

[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.

Elective ilioingunial lymph node irradiation

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

Henderson, R.H.; Parsons, J.T.; Morgan, L.

1984-06-01

Most radiologists accept that modest doses of irradiation (4500-5000 rad/4 1/2-5 weeks) can control subclinical regional lymph node metastases from squamous cell carcinomas of the head and neck and adenocarcinomas of the breast. There have been few reports concerning elective irradiation of the ilioinguinal region. Between October 1964 and March 1980, 91 patients whose primary cancers placed the ilioinguinal lymph nodes at risk received elective irradiation at the University of Florida. Included are patients with cancers of the vulva, penis, urethra, anus and lower anal canal, and cervix or vaginal cancers that involved the distal one-third of the vagina. Inmore » 81 patients, both inguinal areas were clinically negative; in 10 patients, one inguinal area was positive and the other negative by clinical examination. The single significant complication was a bilateral femoral neck fracture. The inguinal areas of four patients developed mild to moderate fibrosis. One patient with moderate fibrosis had bilateral mild leg edema that was questionably related to irradiation. Complications were dose-related. The advantages and dis-advantages of elective ilioinguinal node irradiation versus elective inguinal lymph node dissection or no elective treatment are discussed.« less

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.

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.

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.

Axillary Ultrasound Accurately Excludes Clinically Significant Lymph Node Disease in Patients with Early Stage Breast Cancer

PubMed Central

Tucker, Natalia S.; Cyr, Amy E.; Ademuyiwa, Foluso O.; Tabchy, Adel; George, Krystl; Sharma, Piyush; Jin, Linda X.; Sanati, Souzan; Aft, Rebecca; Gao, Feng; Margenthaler, Julie A.; Gillanders, William E.

2016-01-01

Objective Assess the performance characteristics of axillary ultrasound (AUS) for accurate exclusion of clinically significant axillary lymph node (ALN) disease. Background Sentinel lymph node biopsy (SLNB) is currently the standard of care for staging the axilla in patients with clinical T1–T2, N0 breast cancer. AUS is a noninvasive alternative to SLNB for staging the axilla. Methods Patients were identified using a prospectively maintained database. Sensitivity, specificity, and negative predictive value (NPV) were calculated by comparing AUS findings to pathology results. Multivariate analyses were performed to identify patient and/or tumor characteristics associated with false negative (FN) AUS. A blinded review of FN and matched true negative cases was performed by two independent medical oncologists to compare treatment recommendations and actual treatment received. Recurrence-free survival was described using Kaplan-Meier product limit methods. Results 647 patients with clinical T1–T2, N0 breast cancer underwent AUS between January, 2008 and March, 2013. AUS had a sensitivity of 70%, NPV of 84% and PPV of 56% for the detection of ALN disease. For detection of clinically significant disease (> 2.0 mm), AUS had a sensitivity of 76% and NPV of 89%. FN AUS did not significantly impact adjuvant medical decision making. Patients with FN AUS had recurrence-free survival equivalent to patients with pathologic N0 disease. Conclusions AUS accurately excludes clinically significant ALN disease in patients with clinical T1–T2, N0 breast cancer. AUS may be an alternative to SLNB in these patients where axillary surgery is no longer considered therapeutic, and predictors of tumor biology are increasingly used to make adjuvant therapy decisions. PMID:26779976

[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.

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.

[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.

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.

Obstructive Jaundice as an Uncommon Manifestation of Metastatic Breast Cancer.

PubMed

Budimir, Ivan; Sabol Pusic, Mateja; Nikolic, Marko; Dorosulic, Zdravko; Ljubicic, Neven; Stajduhar, Emil; Mise, Ivana; Vazdar, Ljubica; Sarcevic, Bozena

2015-02-01

Invasive ductal carcinoma is the most common type of breast cancer and accounts for about 70-85% of all invasive breast carcinomas. It primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain. Most of breast cancer recurrence occurs within the first 5 years of diagnosis, particularly for ER negative disease. Gastrointestinal tract involvement is very rare and is detected in only 10% of all the cases, and it usually derives from lobular breast cancer rather than the much more common cell type of ductal breast cancer. Early diagnosis is very important because it enables prompt and adequate choice of treatment and improves patient's long-term prognosis. In this report we describe an unusual case of obstructive jaundice caused by metastases from invasive ductal breast cancer to the lymph nodes of the hepatoduodenal ligament with extramural compression of the distal common bile duct and tumor invasion to the lumen of the duct. Our goal is to emphasize possible diagnostic pitfalls and increase the clinical awareness and the importance of intensive follow-up in patients with breast cancer, even years after the initial diagnosis.

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

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.

[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.

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.

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

[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.

Availability of sentinel lymph node biopsy for cutaneous squamous cell carcinoma.

PubMed

Maruyama, Hiroshi; Tanaka, Ryota; Fujisawa, Yasuhiro; Nakamura, Yasuhiro; Ito, Shusaku; Fujimoto, Manabu

2017-04-01

Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty-nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow-up period were included. Forty-nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false-negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post-treatment metastases. The metastasis-free and disease-specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2-T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis-free and disease-specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging. © 2016 Japanese Dermatological Association.

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.

Management of In-Breast Tumor Recurrence.

PubMed

Wong, Stephanie M; Golshan, Mehra

2018-06-26

The management of isolated in-breast tumor recurrence is complex, requiring careful consideration of prior local therapies to plan future multimodality treatment. Options for surgical management have evolved from standard salvage mastectomy with axillary clearance and now include repeat breast conservation with axillary staging in select patients. Reattempting sentinel lymph node biopsy may avoid the morbidity of extensive axillary surgery and has been shown to be feasible in clinically node-negative patients with oncologically safe outcomes. In the adjuvant setting, partial breast irradiation has emerged as a valuable means to improve local control rates with limited associated toxicity and acceptable overall cosmesis. Furthermore, results from prospective trials are now available to support the use of chemotherapy in hormone-receptor negative subgroups, which is associated with improvements in long-term, disease-free, and overall survival.

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.

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

Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

PubMed

Hyun, Su Jeong; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung

2016-11-01

To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. • Breast MRI can be used to exclude advanced nodal disease (pN2-3). • Negative MRI allows breast cancer patients to avoid unnecessary axillary surgery (98.2 %). • Negative MRI findings exclude 99.6 % of pN2-pN3 in the no-NAC group. • Negative MRI findings exclude 96.0 % of pN2-pN3 in the NAC group.

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.

Oncogenic role of SIRT1 associated with tumor invasion, lymph node metastasis, and poor disease-free survival in triple negative breast cancer.

PubMed

Chung, Soo Young; Jung, Yoon Yang; Park, In Ae; Kim, Hyojin; Chung, Yul Ri; Kim, Ji Young; Park, Soo Young; Im, Seock-Ah; Lee, Kyung-Hun; Moon, Hyeong-Gon; Noh, Dong-Young; Han, Wonshik; Lee, Chul; Kim, Tae-Yong; Ryu, Han Suk

2016-02-01

The aim of this study is to evaluate the biological role and clinical implications of silent mating type information regulation 2 homolog 1 (SIRT1) as a novel candidate for target therapy in triple negative breast cancer (TNBC) for which there is no specific agent. 344 patients who received surgical resection for TNBC from January 2003 to December 2006 at Seoul National University Hospital were enrolled, and the role of SIRT1 protein was evaluated via immunohistochemistry on tissue samples. In vivo experiments to evaluate tumor invasiveness were carried out with three human TNBC cell lines following SIRT1-siRNA transfection. Expression of SIRT1 significantly correlated with lymph node metastasis (p = 0.008). In multivariate analysis, SIRT1 expression (p = 0.011), T stage (p = 0.014), and lymphatic invasion (p < 0.001) were revealed to be independent predictive factors for lymph node metastasis. Combination of these three parameters revealed predictive performance for lymph node metastasis with an area under the curve (AUC) of 0.689 on receiver operating characteristics (ROC) curves analysis. SIRT1 expression correlated with shorter disease-free survival (P = 0.003) but not with overall survival. Inhibition of SIRT1 with small interfering RNA (siRNA) conspicuously suppressed the invasiveness of TNBC cell lines. This study reveals the role of SIRT1 on tumor invasiveness and unfavorable clinical outcomes, and we suggest its potential role as a prognostic indicator as well as a novel therapeutic target in TNBC.

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.

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.

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.

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.

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.

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

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.

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.

[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.

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

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

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.

Paired-agent fluorescent imaging to detect micrometastases in breast sentinel lymph node biopsy: experiment design and protocol development

NASA Astrophysics Data System (ADS)

Li, Chengyue; Xu, Xiaochun; Basheer, Yusairah; He, Yusheng; Sattar, Husain A.; Brankov, Jovan G.; Tichauer, Kenneth M.

2018-02-01

Sentinel lymph node status is a critical prognostic factor in breast cancer treatment and is essential to guide future adjuvant treatment. The estimation that 20-60% of micrometastases are missed by conventional pathology has created a demand for the development of more accurate approaches. Here, a paired-agent imaging approach is presented that employs a control imaging agent to allow rapid, quantitative mapping of microscopic populations of tumor cells in lymph nodes to guide pathology sectioning. To test the feasibility of this approach to identify micrometastases, healthy pig lymph nodes were stained with targeted and control imaging agent solution to evaluate the potential for the agents to diffuse into and out of intact nodes. Aby-029, an anti-EGFR affibody was labeled with IRDye 800CW (LICOR) as targeted agent and IRDye 700DX was hydrolyzed as a control agent. Lymph nodes were stained and rinsed by directly injecting the agents into the lymph nodes after immobilization in agarose gel. Subsequently, lymph nodes were frozen-sectioned and imaged under an 80-um resolution fluorescence imaging system (Pearl, LICOR) to confirm equivalence of spatial distribution of both agents in the entire node. The binding potentials were acquired by a pixel-by-pixel calculation and was found to be 0.02 +/- 0.06 along the lymph node in the absence of binding. The results demonstrate this approach's potential to enhance the sensitivity of lymph node pathology by detecting fewer than 1000 cell in a whole human lymph node.

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

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.

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.

The CD200-tolerance signaling molecule associated with pregnancy success is present in patients with early-stage breast cancer but does not favor nodal metastasis.

PubMed

Clark, David A; Dhesy-Thind, Sukhbinder; Ellis, Peter; Ramsay, Jennifer

2014-11-01

The CD200-tolerance signaling molecule prevents pregnancy failure and is also expressed by a wide variety of malignant tumors. The effect of CD200 mRNA expression on progression of human tumors has been variable. A cross-sectional study was performed to examine the correlation between CD200 protein expression in the primary tumors from postoperative Stage I-IIIA human breast cancer and the likelihood of regional lymph node metastasis. Fifty-eight percentage of patients had strong CD200(+) tumor staining (71% of Stage I and 53% Stage II-IIIA). Strong staining was associated with large T2-3 primary tumors compared to T1 tumors (64 versus 50%) and T2-3 N(+) versus T1 N(-) tumors (70 versus 63%), but this was not statistically significant. Nodal metastases were not more frequent in patients with strong CD200(+) staining (57% compared to 58% for weak/negative staining cases), and the metastatic tumor cells in regional lymph nodes were often CD200(-) when the primary tumor was CD200(+). CD200 expression by early-stage human breast cancer cells in primary tumors did not correlate with increased regional lymph node metastasis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma.

PubMed

Mantel, Hendrik T J; Wiggers, Jim K; Verheij, Joanne; Doff, Jan J; Sieders, Egbert; van Gulik, Thomas M; Gouw, Annette S H; Porte, Robert J

2015-12-01

Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.

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.

Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy.

PubMed

Ramírez-Backhaus, Miguel; Mira Moreno, Alejandra; Gómez Ferrer, Alvaro; Calatrava Fons, Ana; Casanova, Juan; Solsona Narbón, Eduardo; Ortiz Rodríguez, Isabel María; Rubio Briones, José

2016-11-01

We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph fluorescent analysis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

PubMed Central

Ma, Michelle W.; Medicherla, Ratna C.; Qian, Meng; de Miera, Eleazar Vega-Saenz; Friedman, Erica B.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Ott, Patrick A.; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod

2013-01-01

The sentinel lymph node is the initial site of metastasis. Down-regulation of anti-tumor immunity plays a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T-cells (Foxp3+) and dendritic cells (conventional: CD11c+, mature: CD86+) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunologic primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared to those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T-cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathologic variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Anti-tumor immunity was down-regulated in the positive sentinel lymph node with an increase in regulatory T-cells compared to the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared to the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T-cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions. PMID:22425909

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.

Normal Axillary Lymph Node Variability Between White and Black Women on Breast MRI.

PubMed

Grimm, Lars J; Viradia, Neal K; Johnson, Karen S

2018-03-01

This study aimed to determine if there were differences in the imaging features of normal lymph nodes between white and black women using magnetic resonance imaging. Following institutional review board approval, we identified white and black women who underwent breast magnetic resonance imaging from November 1, 2008 to December 31, 2013 at our institution. To identify normal lymph nodes for measurement, patients with any benign or malignant causes for lymph node enlargement and patients with any subsequent breast cancer in the following 2 years were excluded. Black and white women were age matched at a 1:2 ratio. The largest lymph node in each axilla was measured for the long-axis length and maximal cortical thickness. Comparisons were made between white and black women using a conditional logistic regression to control for matching. There were 55 black women and 110 white women for analysis. The mean lymph node long-axis length was 14.7 ± 5.3 mm for black women and 14.4 ± 6.4 mm for white women (P = .678). The mean maximum cortical thickness was 3.3 ± 1.6 mm for black women and 2.6 ± 1.4 mm for Caucasian women (P < .001). A significantly higher percentage of black than white women had cortical thicknesses greater than threshold values of 3, 4, 5, 6, and 7 mm (P < .01 for all). The normal lymph node cortical thickness in black women is significantly greater than in white women, which should be considered when deciding to recommend a lymph node biopsy. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

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.

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.

Axillary lymph nodes and arm lymphatic drainage pathways are spared during routine complete axillary clearance in majority of women undergoing breast cancer surgery.

PubMed

Szuba, A; Chachaj, Z; Koba-Wszedybylb, M; Hawro, R; Jasinski, R; Tarkowski, R; Szewczyk, K; Bebenek, M; Forgacz, J; Jodkowska, A; Jedrzejuk, D; Janczak, D; Mrozinska, M; Pilch, U; Wozniewski, M

2011-09-01

Alterations in axillary lymph nodes (ALNs) after complete axillary lymph node dissection (ALND) in comparison to the preoperative status were evaluated using lymphoscintigraphy performed preoperatively and 1-6 weeks after surgery in 30 women with a new diagnosis of unilateral, invasive breast carcinoma. Analysis of lymphoscintigrams revealed that ALNs after surgery were present in 26 of 30 examined women. In comparison to preoperative status, they were visualized in the same location (12 women), in the same and additionally in different locations (9 women), or only in different locations (4 women). No lymph nodes were visualized in one woman and lymphocoele were in 4 women. Thus, after ALND, a variable number of axillary lymph nodes remain and were visualized on lymphoscintigraphy in the majority of women. The classical ALND, therefore, does not allow complete dissection and removal of axillary nodes with total disruption of axillary lymphatic pathways, accounting in part for the variable incidence and severity of lymphedema after the procedure.

[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.

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.

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

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

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.

Impact of false-negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma.

PubMed

Caracò, C; Marone, U; Celentano, E; Botti, G; Mozzillo, N

2007-09-01

Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.

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.

Targeting mrtl to Reverse Myc in Breast Oncogenesis

DTIC Science & Technology

2011-06-01

overlying skin , perineural invasion, lymphovascular invasion, 1/14 lymph nodes positive metastatic carcinoma with extranodal extension, 2.5 cm pT4b...successfully acquired an additional 8 primary invasive breast carcinoma specimens, 1 metastatic lesion of breast tumor origin, 3 adjacent uninvolved...Her2-neu-positive, lobular features, 21 cm, modified Bloom-Richardson grade III/III, ypT3; N2. metastatic carcinoma involving 4/11 lymph nodes

Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes.

PubMed

von Minckwitz, Gunter; Untch, Michael; Blohmer, Jens-Uwe; Costa, Serban D; Eidtmann, Holger; Fasching, Peter A; Gerber, Bernd; Eiermann, Wolfgang; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kaufmann, Manfred; Konecny, Gottfried E; Denkert, Carsten; Nekljudova, Valentina; Mehta, Keyur; Loibl, Sibylle

2012-05-20

The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain. Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven randomized trials were analyzed. Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) -negative (P = .005), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis. pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

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.

What Is a False Negative Sentinel Node Biopsy: Definition, Reasons and Ways to Minimize It?

PubMed

Kataria, Kamal; Srivastava, Anurag; Qaiser, Darakhshan

2016-10-01

Sentinel node biopsy helps in assessing the involvement of axillary lymph node without the morbidity of full axillary lymph node dissection, namely arm and shoulder pain, paraesthesia and lymphoedema. The various methods described in the literature identify the sentinel lymph nodes in approximately 96 % of cases and associated with a false negativity rate of 5 to 10 %. A false negative sentinel node is defined as the proportion of cases in whom sentinel node biopsy is reported as negative, but the rest of axillary lymph node(s) harbours cancer cells. The possible causes of a false negative sentinel lymph node may be because of blocked lymphatics either by cancer cells or following fibrosis of previous surgery/radiotherapy, and an alternative pathway opens draining the blue dye or isotope to another uninvolved node . The other reasons may be two lymphatic pathways for a tumour area, the one opening to a superficial node and the other in deep nodes. Sometimes, lymphatics do not relay into a node but traverse it going to a higher node. In some patients, the microscopic focus of metastasis inside a lymph node is so small-micrometastasis (i.e. between 0.2 and 2 mm) or isolated tumour cells (i.e. less than 0.2 mm) that is missed by the pathologist. The purpose of this review is to clear some fears lurking in the mind of most surgeons about the false negative sentinel lymph node (FNSLN).

[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.

The role of MRI in axillary lymph node imaging in breast cancer patients: a systematic review.

PubMed

Kuijs, V J L; Moossdorff, M; Schipper, R J; Beets-Tan, R G H; Heuts, E M; Keymeulen, K B M I; Smidt, M L; Lobbes, M B I

2015-04-01

To assess whether MRI can exclude axillary lymph node metastasis, potentially replacing sentinel lymph node biopsy (SLNB), and consequently eliminating the risk of SLNB-associated morbidity. PubMed, Cochrane, Medline and Embase databases were searched for relevant publications up to July 2014. Studies were selected based on predefined inclusion and exclusion criteria and independently assessed by two reviewers using a standardised extraction form. Sixteen eligible studies were selected from 1,372 publications identified by the search. A dedicated axillary protocol [sensitivity 84.7 %, negative predictive value (NPV) 95.0 %] was superior to a standard protocol covering both the breast and axilla simultaneously (sensitivity 82.0 %, NPV 82.6 %). Dynamic, contrast-enhanced MRI had a lower median sensitivity (60.0 %) and NPV (80.0 %) compared to non-enhanced T1w/T2w sequences (88.4, 94.7 %), diffusion-weighted imaging (84.2, 90.6 %) and ultrasmall superparamagnetic iron oxide (USPIO)- enhanced T2*w sequences (83.0, 95.9 %). The most promising results seem to be achievable when using non-enhanced T1w/T2w and USPIO-enhanced T2*w sequences in combination with a dedicated axillary protocol (sensitivity 84.7 % and NPV 95.0 %). The diagnostic performance of some MRI protocols for excluding axillary lymph node metastases approaches the NPV needed to replace SLNB. However, current observations are based on studies with heterogeneous study designs and limited populations. • Some axillary MRI protocols approach the NPV of an SLNB procedure. • Dedicated axillary MRI is more accurate than protocols also covering the breast. • T1w/T2w protocols combined with USPIO-enhanced sequences are the most promising sequences.

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.

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

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.

Evaluation of the tracing effect of carbon nanoparticle and carbon nanoparticle-epirubicin suspension in axillary lymph node dissection for breast cancer treatment.

PubMed

Du, Junze; Zhang, Yongsong; Ming, Jia; Liu, Jing; Zhong, Ling; Liang, Quankun; Fan, Linjun; Jiang, Jun

2016-06-22

Carbon nanoparticle suspension, using smooth carbon particles at a diameter of 21 nm added with suspending agents, is a stable suspension of carbon pellets of 150 nm in diameter. It is obviously inclined to the lymphatic system. There were some studies reporting that carbon nanoparticles are considered as superior tracers for sentinel lymph nodes because of their stability and operational feasibility. However, there were few study concerns about the potential treatment effect including tracing and local chemotherapeutic effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. In the current study, a randomized controlled analysis was performed to investigate the potential treatment effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. A total of 90 breast cancer patients were randomly divided into three equal groups: control, tracer, and drug-load groups. The control group patients did not receive any lymphatic tracers, the tracer group patients were subcutaneously injected with 1 ml carbon nanoparticle suspension, and the drug-load group patients were injected with 3 ml carbon nanoparticle-epirubicin suspension at four separate sites around the areola 24 h before surgery. Modified radical mastectomy, endoscopic subcutaneous mammary resection plus axillary lymph node dissection, and immediate reconstruction with implants or breast-conserving surgery were performed. The mean number of the dissected lymph nodes per patient was significantly higher in the tracer (21.3 ± 6.1) and drug-load (19.5 ± 3.7) groups than in the control group (16.7 ± 3.4) (P < 0.05). Most lymph nodes in the former two groups were stained black (75.7 and 73.3 %, respectively), but with no significant difference between the groups. Most metastatic lymph nodes were also stained black in the tracer group (68.6 %) and drug-load group (78.1 %) and with no significant difference between the groups (P = 0.198). Microscopic examination revealed that the carbon nanoparticles were localized around or among the cancer cell masses and residues of necrotized cancer cells surrounded by fibroblastic proliferation could be found within the stained lymph nodes in the drug-load group. The majority of axillary lymph nodes were stained black by the suspension of carbon nanoparticles, which helped identify the lymph nodes from the surrounding tissues and avoided aggressive axillary treatment. Thus, a combination therapy of carbon nanoparticles with epirubicin could play an important role in lymphatic chemotherapy without affecting tracing. ChiCTRTRC13003419.

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

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.

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.

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.

Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

PubMed

Kamrava, Mitchell; Kuske, Robert R; Anderson, Bethany; Chen, Peter; Hayes, John; Quiet, Coral; Wang, Pin-Chieh; Veruttipong, Darlene; Snyder, Margaret; Demanes, David J

2018-06-01

To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive 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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

Patterns of care in Dutch postmenopausal patients with hormone-sensitive early breast cancer participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

PubMed

van Nes, J G H; Seynaeve, C; Maartense, E; Roumen, R M H; de Jong, R S; Beex, L V A M; Meershoek-Klein Kranenbarg, W M; Putter, H; Nortier, J W R; van de Velde, C J H

2010-05-01

The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < or =2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.

MRI and (31)P magnetic resonance spectroscopy hardware for axillary lymph node investigation at 7T.

PubMed

Rivera, Debra S; Wijnen, Jannie P; van der Kemp, Wybe J M; Raaijmakers, Alexander J; Luijten, Peter R; Klomp, Dennis W J

2015-05-01

Neoadjuvant treatment response in lymph nodes predicts patient outcome, but existing methods do not track response during therapy accurately. In this study, specialized hardware was used to adapt high-field (7T) (31) P magnetic resonance spectroscopy (MRS), which has been shown to track treatment response in small breast tumors, to monitor axillary lymph nodes. A dual-tuned quadrature coil that is a (31) P (120 MHz) transceiver and a (1) H (300 MHz) receiver was designed using a novel detune circuit. The transceiver/receiver coil in the axilla is used with a fractionated dipole antenna on the back of the subject and the conventional breast coil for transmit. The novel circuit detuned the (1) H resonance without disturbing the (31) P resonance. In vivo demonstrations included: >80% homogeneous B1 (+) for (1) H over the axilla, identification of a small (3-mm diameter) lymph node, and (31) P MR spectra from a single healthy lymph node. The setup can detect <2 millimolar concentrations of metabolites from a 2-mL voxel. The first (31) P MR spectrum from an in vivo lymph node indicates that the presented design may be sufficiently sensitive to detect metabolic response to neoadjuvant therapy. Multinuclei MRS of the lymph nodes at 7T is possible through combining lightweight antenna elements with dual-tuned transceiver/receive-only coils. © 2014 Wiley Periodicals, Inc.

[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.

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.

A handheld SPIO-based sentinel lymph node mapping device using differential magnetometry

NASA Astrophysics Data System (ADS)

Waanders, S.; Visscher, M.; Wildeboer, R. R.; Oderkerk, T. O. B.; Krooshoop, H. J. G.; ten Haken, B.

2016-11-01

Sentinel lymph node biopsy has become a staple tool in the diagnosis of breast cancer. By replacing the morbidity-plagued axillary node clearance with removing only those nodes most likely to contain metastases, it has greatly improved the quality of life of many breast cancer patients. However, due to the use of ionizing radiation emitted by the technetium-based tracer material, the current sentinel lymph node biopsy has serious drawbacks. Most urgently, the reliance on radioisotopes limits the application of this procedure to small parts of the developed world, and it imposes restrictions on patient planning and hospital logistics. Magnetic alternatives have been tested in recent years, but all have their own drawbacks, mostly related to interference from metallic instruments and electromagnetic noise coming from the human body. In this paper, we demonstrate an alternative approach that utilizes the unique nonlinear magnetic properties of superparamagnetic iron oxide nanoparticles to eliminate the drawbacks of both the traditional gamma-radiation centered approach and the novel magnetic techniques pioneered by others. Contrary to many other nonlinear magnetic approaches however, field amplitudes are limited to 5 mT, which enables handheld operation without additional cooling. We show that excellent mass sensitivity can be obtained without the need for external re-balancing of the probe to negate any influences from the human body. Additionally, we show how this approach can be used to suppress artefacts resulting from the presence of metallic instruments, which are a significant dealbreaker when using conventional magnetometry-based approaches.

Technical details of sentinel lymph node mapping in colorectal cancer and its impact on staging.

PubMed

Saha, S; Wiese, D; Badin, J; Beutler, T; Nora, D; Ganatra, B K; Desai, D; Kaushal, S; Nagaraju, M; Arora, M; Singh, T

2000-03-01

Sentinel lymph node (SLN) mapping for melanoma and breast cancer has greatly enhanced the identification of micrometastases in many patients, thereby upstaging a subset of these patients. The purpose of this study was to see if SLN mapping technique could be used to identify SLNs in colorectal cancer and to assess its impact on pathological staging and treatment. At the time of surgery, 1 ml of Lymphazurin 1% was injected subserosally around the tumor without injecting into the lumen. The first to fourth blue nodes identified were considered the SLNs, which have the highest probability to contain metastases. A standard oncological resection of the bowel was then performed. Multilevel microsections of the SLNs, including a detailed pathological examination of the entire specimen, was performed. SLN was successfully identified in 85 (98.8%) of 86 patients. In 85 patients, there were 1,367 (16 per patient) lymph nodes examined, of which 140 (1.6 per patient) were identified as SLNs. In 53 (95%) of 56, of whom the SLNs were without metastases (negative), all other non-SLNs also were negative. In 29 (34% of 85) patients, SLNs were positive for metastases; in 14 of the 29 patients, other non-SLNs also were positive in addition to the SLNs. In the other 15 of the 29 patients (18% of 85 patients), SLNs were the only site of metastases, and all other non-SLNs were negative. In 7 patients (8.2% of 85 patients), micrometastases were identified only in 1 or 2 of the 10 sections of a single SLN. In five of seven patients, such micrometastases were detected by hematoxylin and eosin staining and immunohistochemistry; in the other two patients, it was detected only by immunohistochemistry. In patients with negative SLNs, the rate of occurrence of micrometastases in non-SLNs was 5 (0.4%) of 1,184 lymph nodes. SLN mapping can be performed easily in colorectal cancer patients, with an accuracy of more than 95%. The identification of submicroscopic lymph node metastases by this technique may have upstaged these patients (18%) from stage I/II to stage III disease, who may then benefit from further adjuvant chemotherapy.

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.

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

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

Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women With Squamous Cell Carcinoma of the Vulva: A Gynecologic Oncology Group Study

PubMed Central

Levenback, Charles F.; Ali, Shamshad; Coleman, Robert L.; Gold, Michael A.; Fowler, Jeffrey M.; Judson, Patricia L.; Bell, Maria C.; De Geest, Koen; Spirtos, Nick M.; Potkul, Ronald K.; Leitao, Mario M.; Bakkum-Gamez, Jamie N.; Rossi, Emma C.; Lentz, Samuel S.; Burke, James J.; Van Le, Linda; Trimble, Cornelia L.

2012-01-01

Purpose To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. Patients and Methods Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. Results In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). Conclusion Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva. PMID:22753905

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.

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.

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.

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

Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

PubMed

Noh, J M; Park, W; Suh, C-O; Keum, K C; Kim, Y B; Shin, K H; Kim, K; Chie, E K; Ha, S W; Kim, S S; Ahn, S D; Shin, H S; Kim, J H; Lee, H-S; Lee, N K; Huh, S J; Choi, D H

2014-03-18

To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II–III breast cancer? A multicentre retrospective study (KROG 12-05)

PubMed Central

Noh, J M; Park, W; Suh, C-O; Keum, K C; Kim, Y B; Shin, K H; Kim, K; Chie, E K; Ha, S W; Kim, S S; Ahn, S D; Shin, H S; Kim, J H; Lee, H-S; Lee, N K; Huh, S J; Choi, D H

2014-01-01

Background: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II–III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). Methods: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. Results: After a median follow-up period of 66.2 months (range, 15.6–127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0−is vs 1 vs 2–4) and the number of LNs sampled (<13 vs ⩾13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. Conclusions: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials. PMID:24481403

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients.

PubMed

Ryan, Marisa; Crow, Jennifer; Kahmke, Russel; Fisher, Samuel R; Su, Zuowei; Lee, Walter T

2014-01-01

1) Assess FoxP3/indoleamine 2,3-dioxygenase immunoreactivity in head and neck melanoma sentinel lymph nodes and 2) correlate FoxP3/indoleamine 2,3-dioxygenase with sentinel lymph node metastasis and clinical recurrence. Retrospective cohort study. Patients with sentinel lymph node biopsy for head and neck melanoma between 2004 and 2011 were identified. FoxP3/indoleamine 2,3-dioxygenase prevalence and intensity were determined from the nodes. Poor outcome was defined as local, regional or distant recurrence. The overall immunoreactivity score was correlated with clinical recurrence and sentinel lymph node metastasis using the chi-square test for trend. Fifty-six sentinel lymph nodes were reviewed, with 47 negative and 9 positive for melanoma. Patients with poor outcomes had a statistically significant trend for higher immunoreactivity scores (p=0.03). Positive nodes compared to negative nodes also had a statistically significant trend for higher immunoreactivity scores (p=0.03). Among the negative nodes, there was a statistically significant trend for a poor outcome with higher immunoreactivity scores (p=0.02). FoxP3/indoleamine 2,3-dioxygenase immunoreactivity correlates with sentinel lymph node positivity and poor outcome. Even in negative nodes, higher immunoreactivity correlated with poor outcome. Therefore higher immunoreactivity may portend a worse prognosis even without metastasis in the sentinel lymph node. This could identify a subset of patients that may benefit from future trials and treatment for melanoma through Treg and IDO suppression. Published by Elsevier Inc.

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.

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.

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

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.

Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery.

PubMed

Ashitate, Yoshitomo; Hyun, Hoon; Kim, Soon Hee; Lee, Jeong Heon; Henary, Maged; Frangioni, John V; Choi, Hak Soo

2014-01-01

The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We developed near-infrared fluorophores, which have fluorescence emission maxima either at 700 nm or at 800 nm. One was injected intravenously for identification of all regional lymph nodes in a basin, and the other was injected locally for identification of the SLN. Using the dual-channel FLARE intraoperative imaging system, we could identify and resect all PLNs and SLNs simultaneously. The technology we describe enables simultaneous, real-time visualization of both PLNs and SLNs in the same subject.

Imaging of Lymph Flow in Breast Cancer Patients after Microdose Administration of a Near-Infrared Fluorophore: Feasibility Study1

PubMed Central

Sevick-Muraca, Eva M.; Sharma, Ruchi; Rasmussen, John C.; Marshall, Milton V.; Wendt, Juliet A.; Pham, Hoang Q.; Bonefas, Elizabeth; Houston, Jessica P.; Sampath, Lakshmi; Adams, Kristen E.; Blanchard, Darlene Kay; Fisher, Ronald E.; Chiang, Stephen B.; Elledge, Richard; Mawad, Michel E.

2011-01-01

Purpose To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods Informed consent was obtained from 24 women (age range, 30–85 years) who received intradermal subcutaneous injections of 0.31–100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between “packets” of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. Conclusion NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs. PMID:18223125

Isolated perifacial lymph node metastasis in oral squamous cell carcinoma with clinically node-negative neck.

PubMed

Agarwal, Sangeet Kumar; Arora, Sowrabh Kumar; Kumar, Gopal; Sarin, Deepak

2016-10-01

The incidence of occult perifacial nodal disease in oral cavity squamous cell carcinoma is not well reported. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. The study will shed light on current controversies and will provide valuable clinical and pathological information in the practice of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. Prospective analysis. This study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of the metastatic rate to different lymph node levels in 231 patients of oral squamous cell cancer with a clinically node-negative neck. The current study demonstrated that 19 (8.22%) out of 231 patients showed ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial nodes did not differ significantly between the oral tongue (7.14%) and buccal mucosa (7.75%). Incidence was statistically significant in cases with lower age group (<45 years), advanced T stage, and higher depth of tumor invasion. Isolated perifacial node metastasis is high in oral squamous cell carcinoma with a clinically node-negative neck. The incidence of isolated perifacial involvement is high in cases of buccal mucosal and tongue cancers. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. 4 Laryngoscope, 126:2252-2256, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

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.

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.

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 lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma.

PubMed

Yamamoto, Maki; Fisher, Kate J; Wong, Joyce Y; Koscso, Jonathan M; Konstantinovic, Monique A; Govsyeyev, Nicholas; Messina, Jane L; Sarnaik, Amod A; Cruse, C Wayne; Gonzalez, Ricardo J; Sondak, Vernon K; Zager, Jonathan S

2015-05-15

Sentinel lymph node biopsy (SLNB) is indicated for the staging of clinically lymph node-negative melanoma of intermediate thickness, but its use is controversial in patients with thick melanoma. From 2002 to 2012, patients with melanoma measuring ≥4 mm in thickness were evaluated at a single institution. Associations between survival and clinicopathologic characteristics were explored. Of 571 patients with melanomas measuring ≥4 mm in thickness and no distant metastases, the median age was 66 years and 401 patients (70.2%) were male. The median Breslow thickness was 6.2 mm; the predominant subtype was nodular (45.4%). SLNB was performed in 412 patients (72%) whereas 46 patients (8.1%) presented with clinically lymph node-positive disease and 113 patients (20%) did not undergo SLNB. A positive SLN was found in 161 of 412 patients (39.1%). For SLNB performed at the study institution, 14 patients with a negative SLNB developed disease recurrence in the mapped lymph node basin (false-negative rate, 12.3%). The median disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) for the entire cohort were 62.1 months, 42.5 months, and 21.2 months, respectively. The DSS and OS for patients with a negative SLNB were 82.4 months and 53.4 months, respectively; 41.2 months and 34.7 months, respectively, for patients with positive SLNB; and 26.8 months and 22 months, respectively, for patients with clinically lymph node-positive disease (P<.0001). The median RFS was 32.4 months for patients who were SLNB negative, 14.3 months for patients who were SLNB positive, and 6.8 months for patients with clinically lymph node-positive disease (P<.0001). With an acceptably low false-negative rate, patients with thick melanoma and a negative SLNB appear to have significantly prolonged RFS, DSS, and OS compared with those with a positive SLNB. Therefore, SLNB should be considered as indicated for patients with thick, clinically lymph node-negative melanoma. © 2015 American Cancer Society.

Surgeon bias in sentinel lymph node dissection: Do tumor characteristics influence decision making?

PubMed

Robinson, Kristin A; Pockaj, Barbara A; Wasif, Nabil; Kaufman, Katie; Gray, Richard J

2014-12-01

Determining sentinel lymph nodes (SLNs) in breast cancer staging involves subjective interpretation by the surgeon. We hypothesized patient and tumor characteristics influence number of SLNs harvested. A single-institution, prospectively collected database was queried for breast cancer patients undergoing SLN surgery (2002-2013) and mean SLN counts were compared. There were 2394 SLN biopsies. Mean number of SLNs per patient for the entire cohort was 2.6. Mean number of SLNs removed was greater for patients ≤50 years (2.9 versus 2.6; p < 0.0001). Fewer SLNs were removed with tumors ≤1 cm (2.5 versus 2.6; p = 0.002). Patients with grades 2 or 3 tumors had more SLNs removed than grade 1 (2.6 versus 2.5; p = 0.03). Receipt of neoadjuvant therapy was associated with more SLNs removed (3.0 versus 2.6; p = 0.005). Number of SLNs removed varies based on risk factors for SLN metastasis or false-negative SLN biopsy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mammary lymphoscintigraphy with various radiopharmaceuticals in breast cancer.

PubMed

Imoto, S; Murakami, K; Ikeda, H; Fukukita, H; Moriyama, N

1999-10-01

Sentinel node biopsy (SNB) in breast cancer is a promising surgical technique that avoids unnecessary axillary lymph node dissection. To optimize lymphatic mapping with radiopharmaceuticals, mammary lymphoscintigraphy with 30-50 MBq of technetium-99m-diethylenetriamine pentaacetic acid human serum albumin (99mTc-HSAD), technetium-99m-human serum albumin (99mTc-HSA), or technetium-99m-tin colloid (99mTc-TC) were investigated in 69 cases of primary breast cancer. Dynamic early images were obtained during the first 30 or 40 minutes, and static delayed images were obtained 6 hours after tracer injection. Hot spots as sentinel lymph nodes (SLNs) appeared in 51 of 69 cases (74%): in early images in 27 cases and in delayed images in 24 cases. SLNs were visualized more frequently in 23 of the 26 cases (88%) treated with 99mTc-HSAD and in 21 of the 24 cases (88%) treated with 99mTc-HSA than in only 7 of the 19 cases (37%) treated with 99mTc-TC. In 26 of the 51 cases, SLNs were identified as faint spots in delayed images. There was a significant difference in the first appearance of SLNs on the lymphoscintiscan between 43 cases of dense breast parenchyma and 26 cases of fatty breast parenchyma. These results suggest that 99mTc-HSAD or 99mTc-HSA is acceptable for lymphatic mapping, but in cases which have faint spots in delayed images or fatty breast parenchyma, gamma probe-guided SNB may result in failure or misleading false-negative SLNs.

Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity-a retrospective study of 1214 breast cancer patients.

PubMed

Schröder, Lars; Fricker, Roland; Stein, Roland Gregor; Rink, Thomas; Fitz, Hartmut; Blasius, Sebastian; Wöckel, Achim; Müller, Thomas

2018-06-01

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

USE OF COLLOIDAL RADIOGOLD FOR PREOPERATIVE INTERSTITIAL PREIRRADIATION OF BREAST CANCERS (in German)

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

Mueller, J.H.

1963-01-01

Treatment of early breast cancers by infiltration of the entire parasternal region, the subclavicular area, and the inframammary region with an average of 110 mC of colloidal radiogold dissolved in 140 ml or physiological saline and given in 12 to 14 injections, has proven advantageous. Fourteen days after this treatment a radical mastectomy is performed, followed by postoperative radiation treatment (200 to 400 kv). In 25 patients treated consistently by this procedure 46% of the beta doses to lymph nodes from Au/sup 198/ amounted to more than 5000 r, and an additional 27% received from 1000 to 5000 r. Takingmore » into account the gamma radiation from this isotope, which probably amounts to 2000 r, it is estimated that at least 70% received a therapeutically effective dose to the lymph nodes. Distribution of the radiogold in the lymph nodes has been confirmed histologically, by autoradiographs, and by neutron activation analysis. In 40 patients previously treated by this procedure, who either had no metastases or only a few in the axillary lymph nodes, no recurrence has been noted in the past 10 years. In three patients who died there was evidence of massive neoplasia (carcinomatous mastitis), extensively axillary lymph node involvement, and latent preoperative hematological symptoms. This procedure is not intended to replace classical methods of treatment, but it represents an important advance in treatment of early breast cancer. (BBB)« less

Feasibility of contrast-enhanced ultrasound-guided biopsy of sentinel lymph nodes in dogs.

PubMed

Gelb, Hylton R; Freeman, Lynetta J; Rohleder, Jacob J; Snyder, Paul W

2010-01-01

Our goal was to develop and validate a technique to identify the sentinel lymph nodes of the mammary glands of healthy dogs with contrast-enhanced ultrasound, and evaluate the feasibility of obtaining representative samples of a sentinel lymph node under ultrasound guidance using a new biopsy device. Three healthy intact female adult hounds were anesthetized and each received an injection of octafluoropropane-filled lipid microspheres and a separate subcutaneous injection of methylene blue dye around a mammary gland. Ultrasound was then used to follow the contrast agent through the lymphatic channel to the sentinel lymph node. Lymph node biopsy was performed under ultrasound guidance, followed by an excisional biopsy of the lymph nodes and a regional mastectomy procedure. Excised tissues were submitted for histopathologic examination and evaluated as to whether they were representative of the node. The ultrasound contrast agent was easily visualized with ultrasound leading up to the sentinel lymph nodes. Eight normal lymph nodes (two inguinal, one axillary in two dogs; two inguinal in one dog) were identified and biopsied. Lymphoid tissue was obtained from all biopsy specimens. Samples from four of eight lymph nodes contained both cortical and medullary lymphoid tissue. Contrast-enhanced ultrasound can be successfully used to image and guide minimally invasive biopsy of the normal sentinel lymph nodes draining the mammary glands in healthy dogs. Further work is needed to evaluate whether this technique may be applicable in patients with breast cancer or other conditions warranting evaluation of sentinel lymph nodes in animals.

Current status of sentinel lymph node navigation surgery in breast and gastrointestinal tract.

PubMed

Tangoku, Akira; Seike, Junichi; Nakano, Kiichiro; Nagao, Taeko; Honda, Junko; Yoshida, Takahiro; Yamai, Hiromichi; Matsuoka, Hisashi; Uyama, Kou; Goto, Masakazu; Miyoshi, Takanori; Morimoto, Tadaoki

2007-02-01

Sentinel lymph node biopsy (SLNB) has been developed as a new diagnostic and therapeutic modality in melanoma and breast cancer surgery. The purpose of the SLNB include preventing the operative morbidity and improving the pathologic stage by focusing on fewer lymph nodes using immunocytochemic and molecular technology has almost achieved in breast cancer surgery. The prognostic meaning of immunocytochemically detected micrometastases is also evaluating in the SLN and bone marrow aspirates of women with early-stage breast cancer. SLNB using available techniques have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent because of an aberrant lymphatic drainage outside of the basin exist. At the moment, the available data does not justify reduced extent of lymphadenectomy, but provides strong evidence for an improvement in tumor staging on the basis of SLNB. Two large scale prospective multi-center trials concerning feasibility of gamma-probe and dye detection for gastric cancer are ongoing in Japan. Recent studies have shown favorable results for identification of SLN in esophageal cancer. CT lymphography with endoscopic mucosal injection of iopamidol was applicable for SLN navigation of superficial esophageal cancer. The aim of surgical treatment is complete resection of the tumor-infiltrated organ including the regional lymph nodes. Accurate detection of SLN can achieve a selection of a more sophisticated tailor made approach. The patient can make a individualized choice from a broader spectrum of therapeutic options including endoscopic, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissection. Ultrastaging by detecting micrometastasis at the molecular level and the choice of an adequate treatment improve the postoperative quality of life and survival. However these issues require further investigation.

Concordance Between FISH Analysis of Her-2/Neu Gene in Breast Duct Carcinoma and Corresponding Axillary Nodal Metastases: Egyptian National Cancer Institute Experience.

PubMed

Badawy, Omnia M; Hassan, Hannan; ELBakey, Heba A; Mosaad, Maha

2018-05-10

Breast cancer is a major health problem in Egypt. Her-2/Neu gene is routinely assessed for all breast cancer patients primarily by immunohistochemistry. At National Cancer Institute (NCI), Cairo University, Flourescence In Situ hybridization (FISH) analysis of Her-2/Neu gene is carried out for Her-2/Neu score 2 and for some cases of score 3 (particularly those assessed outside NCI). The test is performed essentially on the primary tumor. However, some situations require testing on corresponding lymph node metastases. There is a debate about the concordance between Her-2/Neu status in the primary tumor and synchronous lymph node metastases in various studies. The aim of this study was to test for the concordance between Her-2/Neu status in the primary breast tumor and corresponding axillary nodal metastases. This is a retrospective study in which FISH analysis of Her-2/Neu was carried out simultaneously on archived material of 50 cases previously diagnosed as invasive duct carcinoma and the corresponding nodal metastases from the Pathology Department, NCI. There was complete concordance between Her-2 status in the primary tumor and the corresponding axillary lymph node metastatic deposits in which Her-2 was amplified in 44% of the studied cohort of Egyptian patients. Her-2/Neu gene assessed by FISH analysis on synchronous lymph node metastases is strongly correlated with the primary tumor. Hence, it is justified to carry out the Her-2/Neu test on synchronous lymph nodes to decide on whether to carry out anti-Her-2/Neu target therapy. Further studies on other metastatic sites is recommended.

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.

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma.

PubMed

Ayadi, Lobna; Khabir, Abdelmajid; Amouri, Habib; Karray, Sondes; Dammak, Abdallah; Guermazi, Mohamed; Boudawara, Tahya

2008-10-22

Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases. This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status. The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002). HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER.

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.

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.

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.).

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.

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 ...

Renal lymph nodes for tumor staging: appraisal of 871 nephrectomies with examination of hilar fat.

PubMed

Mehta, Vikas; Mudaliar, Kumaran; Ghai, Ritu; Quek, Marcus L; Milner, John; Flanigan, Robert C; Picken, Maria M

2013-11-01

Despite decades of research, the role of lymphadenectomy in the management of renal cell carcinoma (RCC) is still not clearly defined. Before the implementation of targeted therapies, lymph node metastases were considered to be a portent of markedly decreased survival, regardless of the tumor stage. However, the role of lymphadenectomy and the relative benefit of retroperitoneal lymph node dissection in the context of modern adjunctive therapies have not been conclusively addressed in the clinical literature. The current pathologic literature does not offer clear recommendations with regard to the minimum number of lymph nodes that should be examined in order to accurately stage the pN in renal cell carcinoma. Although gross examination of the hilar fat to assess the nodal status is performed routinely, it has not yet been determined whether this approach is adequate. To evaluate the status of lymph nodes and their rate of identification in the pathologic examination of nephrectomy specimens in adult renal malignancies. We reviewed the operative and pathology reports of 871 patients with renal malignancies treated by nephrectomy. All tumors were classified according to the seventh edition of the Tumor-Nodes-Metastasis classification. Patients were divided into 3 groups: Nx, no lymph nodes recovered; N0, negative; and N1, with positive lymph nodes. Grossly visible lymph nodes were submitted separately; as per grossing protocol, hilar fatty tissue was submitted for microscopic examination. We evaluated the factors that affected the number of lymph nodes identified and the variables that allowed the prediction of nodal involvement. Lymph nodes were recovered in 333 of 871 patients (38%): hilar in 125 patients, nonhilar in 137 patients, and hilar and nonhilar in 71 patients. Patients with positive lymph nodes (n = 87) were younger, had larger primary tumors, and had lymph nodes of average size, as well as a higher pT stage, nuclear grade, and rate of metastases. Metastases were seen only in grossly identified lymph nodes (65% hilar, 16% nonhilar); all microscopic nodes were negative. Even with the microscopic examination of fat, hilar lymph nodes were recovered in only 22.5% of patients. A nonhilar route of node metastasis was suspected in 40 patients. Only grossly identifiable lymph nodes, both hilar and nonhilar, were positive for metastases. Although microscopic examination of the hilar fat increased the number of lymph nodes recovered, the identification rate of these nodes was low (22.5%), and such microscopic nodes were invariably negative. Hence, microscopic examination of the hilar fat may be unnecessary.

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.

Discordant correlation of breast adenoid cystic carcinoma on imaging and pathology: A case report and literature review on surgical management.

PubMed

Yan, Zhiyan; Leong, May Ying; Lim, Geok Hoon

2018-01-01

Adenoid cystic carcinomas (ACC) of the breast are extremely rare tumours, accounting for <0.1% of newly diagnosed breast cancer cases. Little data exist regarding the correlation of radiological findings with histology of this rare subtype. To our knowledge, gross size discrepancy between the 2 modalities has not been reported. We describe a case of ACC with appreciable size discordance between imaging and pathology report. A 71 years old lady presented with a painless right breast lump of a few months duration. Clinical examination revealed a 1.5 cm right breast upper outer quadrant mass. Axillary and systemic examinations were unremarkable. Mammogram showed an asymmetric density in the right upper outer quadrant which corresponded to a suspicious nodule measuring about 2 cm on the ultrasound. Ultrasound of the axilla showed an indeterminate right lymph node. Core needle biopsy of the right breast nodule showed ACC while the lymph node biopsy was non- metastatic. Staging scans did not reveal any definite distant metastasis. Her naso-endoscopy and MRI of the neck were normal. She underwent a right mastectomy and sentinel lymph node biopsy. Final histology returned as a grade II 55 mm ACC. Lympho-vascular invasion was absent. The tumour was triple negative for Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal receptor 2 (HER 2). Sentinel lymph node biopsy was negative for metastasis. She recovered well but declined adjuvant chemotherapy and radiation therapy. She is currently well 6 months post operation. ACC is an extremely rare subtype, therefore there are limited reports in literature on its imaging and pathological characteristics. Of this sparse data, there was no mention that there might be a big size discrepancy between the 2 modalities. This appreciable discrepancy has implications for pre-operative planning and the choice of breast surgery. It will be useful if the pathological extent of ACC could be determined more accurately radiologically. However, there are no distinctive imaging characteristics for ACC. ACC can appear as a smooth round mass similar to that of a benign mass or as an irregular mass on mammogram. On ultrasound, ACC often manifested as a hypo- echoic heterogeneous mass with minimal vascularity on Doppler imaging and may have an indistinct margin. MRI has a higher sensitivity than mammogram and ultrasound in determining the true extent of the tumour, but there remains little data on its usefulness in ACC. ACC can be extensively infiltrative and present much larger than its radiological size, as reported in our case. Use of better imaging modalities judiciously, in these cases, are needed to more accurately predict the true pathological size of ACC to prevent inadequate surgery. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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.

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.

Tumor implantation model for rapid testing of lymphatic dye uptake from paw to node in small animals

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

2015-03-01

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue - used in the sentinel lymph node procedure - in normal and tumor-bearing animals, and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

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.

A prospective single-center study of sentinel lymph node detection in cervical carcinoma: is there a place in clinical practice?

PubMed

Devaja, Omer; Mehra, Gautam; Coutts, Michael; Montalto, Stephen Attard; Donaldson, John; Kodampur, Mallikarjun; Papadopoulos, Andreas John

2012-07-01

To establish the accuracy of sentinel lymph node (SLN) detection in early cervical cancer. Sentinel lymph node detection was performed prospectively over a 6-year period in 86 women undergoing surgery for cervical carcinoma by the combined method (Tc-99m and methylene blue dye). Further ultrastaging was performed on a subgroup of 26 patients who had benign SLNs on initial routine histological examination. The SLN was detected in 84 (97.7%) of 86 women by the combined method. Blue dye uptake was not seen in 8 women (90.7%). Sentinel lymph nodes were detected bilaterally in 63 women (73.3%), and the external iliac region was the most common anatomic location (48.8%). The median SLN count was 3 nodes (range, 1-7). Of the 84 women with sentinel node detection, 65 also underwent bilateral pelvic lymph node dissection, and in none of these cases was a benign SLN associated with a malignant non-SLN (100% negative predictive value). The median non-SLN count for all patients was 19 nodes (range, 8-35). Eighteen patients underwent removal of the SLN without bilateral pelvic lymph node dissection. Nine women (10.5%) had positive lymph nodes on final histology. One patient had bulky pelvic nodes on preoperative imaging and underwent removal of the negative bulky malignant lymph nodes and a benign SLN on the contralateral side. This latter case confirms the unreliability of the SLN method with bulky nodes. The remaining 8 patients had positive SLNs with negative nonsentinel lymph nodes. Fifty-nine SLNs from 26 patients, which were benign on initial routine histology, underwent ultrastaging, but no further disease was identified. Four patients (5%) relapsed after a median follow-up of 28 months (range, 8-80 months). Sentinel lymph node detection is an accurate and safe method in the assessment of nodal status in early cervical carcinoma.

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

PubMed Central

Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2016-01-01

We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model. PMID:27689331

Sentinel lymph node biopsy in gastrointestinal malignancies-where do we stand?

PubMed

Maharaj, R; Shukla, P J; Naraynsingh, V; Dan, D; Hariharan, S

2011-01-01

Sentinel lymph nodes (SLNs) are the nodes in direct communication with the primary tumor and are therefore the first group of nodes to be involved in lymphatic metastasis. Though the role of SLN biopsy is well established in cancers of the breast and melanoma, its role in gastrointestinal malignancies is still evolving and controversial. In this paper, the literature is reviewed with respect to the status of SLN biopsy in gastrointestinal malignancies.

Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

PubMed

Schaarschmidt, Benedikt Michael; Grueneisen, Johannes; Stebner, Vanessa; Klode, Joachim; Stoffels, Ingo; Umutlu, Lale; Schadendorf, Dirk; Heusch, Philipp; Antoch, Gerald; Pöppel, Thorsten Dirk

2018-06-06

To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma. Fifty-two patients with malignant melanoma (female: n = 30, male: n = 22, mean age 50.5 ± 16.0 years, mean tumor thickness 2.28 ± 1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard. Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true positive findings could not be increased. In conclusion, integrated 18F-FDG PET/MR does not reliably differentiate N-positive from N-negative melanoma patients. Additional DWI does not increase the sensitivity of 18F-FDG PET/MR. Hence, sentinel lymph node biopsy cannot be replaced by 18F-FDG-PE/MR or 18F-FDG-PET/CT.

The use of isotope injections in sentinel node biopsy for breast cancer: are the 1- and 2-day protocols equally effective?

PubMed

Dodia, Nazera; El-Sharief, Deena; Kirwan, Cliona C

2015-01-01

Sentinel lymph nodes are mapped using (99m)Technetium, injected on day of surgery (1-day protocol) or day before (2-day protocol). This retrospective cohort study compares efficacy between the two protocols. Histopathology for all unilateral sentinel lymph node biopsies (March 2012-March 2013) in a single centre were reviewed. Number of sentinel lymph nodes, non-sentinel lymph nodes and pathology was compared. 2/270 (0.7 %) in 1-day protocol and 8/192 (4 %) in 2-day protocol had no sentinel lymph nodes removed (p = 0.02). The median (range) number of sentinel lymph nodes removed per patient was 2 (0-7) and 1 (0-11) in the 1- and 2-day protocols respectively (p = 0.08). There was a trend for removing more non-sentinel lymph nodes in 2-day protocol [1-day: 52/270 (19 %); 2-day: 50/192 (26 %), p = 0.07]. Using 2-day, sentinel lymph node identification failure rate is higher, although within acceptable rates. The 1 and 2 day protocols are both effective, therefore choice of protocol should be driven by patient convenience and hospital efficiency. However, this study raises the possibility that 1-day may be preferable when higher sentinel lymph node count is beneficial, for example following neoadjuvant chemotherapy.

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

[The historical perspective of the sentinel lymph node concept].

PubMed

Bekker, J; Meijer, S

2008-01-05

The sentinel lymph node procedure is currently standard care in the treatment of breast cancer. The introduction of this procedure in 1992 would not have been possible without the pioneering discoveries regarding lymph nodes and cancer. The Italian surgeon Gaspar Asellius (1581-1626) visualized the lymphatic vessels of a dog after it had been fed and shortly before dissection. At the end of the 17th century, the French anatomists Lauth and Sappey visualized the lymphatics by injecting deceased criminals with mercury. In 1858, the German pathologist Virchow (1821-1902) launched the theory that lymph nodes act as defensive barriers. He also made the first microscopical illustration ofa sentinel lymph node. Gould et al. and Cabaãs independently launched the precursors of the current modern sentinel lymph node concept in 1959 and 1977 respectively. Gould et al. were the first people to use the term "sentinel node'. Cabañas used lymphangiography for the visualisation of the sentinel lymph node. Controversies about the barrier function of the lymph nodes, the fear of skip metastasis and the difficulties of performing the Cabañas procedure, prevented a breakthrough of this concept. In 1992 Morton et al. rediscovered the valuable sentinel node biopsy concept and introduced blue dye for the investigation of patients with melanoma. The combination of lymphoscintigraphy, intra-operative gamma probe guidance and patent blue further increased the reliability of the sentinel lymph node biopsy procedure. Unnecessary lymph gland dissection procedures with considerable morbidity can be prevented by this procedure.

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

Indocyanine green detects sentinel lymph nodes in early breast cancer.

PubMed

Liu, Jun; Huang, Linping; Wang, Ning; Chen, Ping

2017-04-01

Objective To explore the clinical value of indocyanine green (ICG) for the fluorescence-guided detection of sentinel lymph nodes (SLNs) during sentinel lymph node biopsy (SLNB) in patients with early breast cancer. Methods This retrospective study included female patients with breast cancer. Patients were administered methylene blue and ICG using standard techniques. All SLNs that were collected during surgery were submitted for pathological examination. SLNs were defined as those that were either fluorescent, blue, fluorescent and blue or palpably suspicious. Surgical complications, axillary recurrence, distant metastasis and overall survival rates were observed postoperatively. Results A total of 60 patients were enrolled in the study. The fluorescence detection rate of SLNs was 100% ( n = 177), with a mean of 2.95 SLNs per patient. The methylene blue staining rate was 88.3% ( n = 106), with a mean of 1.77 SLNs per patient. Pathological assessment of intraoperative frozen specimens revealed SLN metastases in 10 patients, who immediately underwent axillary lymph node dissection. No patient had axillary recurrence or distant metastases, with a survival rate of 100%. Patients who underwent SLNB showed good appearance in the axillary wound, with no limited shoulder joint abduction and upper limb oedema. Conclusion Fluorescence-guided SLNB has several advantages and is suitable for clinical application.

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.

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

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.

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer.

PubMed

Mikosiński, Sławomir; Pomorski, Lech; Oszukowska, Lidia; Makarewicz, Jacek; Adamczewski, Zbigniew; Sporny, Stanisław; Lewiński, Andrzej

2006-01-01

Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.

Fluorescence imaging to study cancer burden on lymph nodes

NASA Astrophysics Data System (ADS)

D'Souza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

2015-03-01

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue along with a cancer targeting tracer, Affibody labeled with IRDYE800CW and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

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.

Interval sentinel lymph nodes in melanoma: a digital pathology analysis of Ki67 expression and microvascular density.

PubMed

Marinaccio, Christian; Giudice, Giuseppe; Nacchiero, Eleonora; Robusto, Fabio; Opinto, Giuseppina; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Domenico

2016-08-01

The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest that the correlation between tumor cell proliferation and neo-angiogenesis in interval sentinel lymph nodes in melanoma could be used as a good predictive marker to distinguish interval positive sentinel lymph nodes with micrometastasis from interval positive lymph nodes with macrometastasis subgroups.

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.

Multicenter Trial of Sentinel Node Biopsy for Breast Cancer Using Both Technetium Sulfur Colloid and Isosulfan Blue Dye

PubMed Central

Tafra, Lorraine; Lannin, Donald R.; Swanson, Melvin S.; Van Eyk, Jason J.; Verbanac, Kathryn M.; Chua, Arlene N.; Ng, Peter C.; Edwards, Maxine S.; Halliday, Bradford E.; Henry, C. Alan; Sommers, Linda M.; Carman, Claire M.; Molin, Melinda R.; Yurko, John E.; Perry, Roger R.; Williams, Robert

2001-01-01

Objective To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). Summary Background Data Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. Methods Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. Results Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. Conclusions This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation. PMID:11141225

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.

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

The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.

PubMed

Remenschneider, Aaron K; Dilger, Amanda E; Wang, Yingbing; Palmer, Edwin L; Scott, James A; Emerick, Kevin S

2015-04-01

Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. Blinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. A consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. Ninety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. SPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

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.

Impact of same day vs day before pre-operative lymphoscintigraphy for sentinel lymph node biopsy for early breast cancer (local Australian experience).

PubMed

Huang, Yang Yang; Maurel, Amelie; Hamza, Saud; Jackson, Lee; Al-Ogaili, Zeyad

2018-06-01

To assess the impact of delayed vs immediate pre-operative lymphoscintigraphy (LSG) for sentinel lymph node biopsy in a single Australian tertiary breast cancer centre. Retrospective cohort study analysing patients with breast cancer or DCIS who underwent lumpectomy or mastectomy with pre-operative LSG and intra-operative sentinel lymph node biopsy from January 2015 to June 2016. A total of 182 LSG were performed. Group A patients had day before pre-operative LSG mapping (n = 79) and Group B had LSG mapping on the day of surgery (n = 103). The overall LSG localisation rate was 97.3% and no statistical difference was detected between the two groups. The overall sentinel lymph node biopsies (SLN) were identified in 99.6% of patients. The number of nodes excised was slightly higher in Group A (1.90 vs 1.72); however, this was not statistically significant. In addition, the number of nodes on histopathology and the incidence of second echelon nodal detection were also similar between the two groups without statistical significance. In conclusion, the 2-day LSG protocol had no impact on overall SLNB and LSG detection rates although slightly higher second tier nodes but this did not translate to any difference between the number of harvest nodes between the two groups. The 2-day LSG allows for greater flexibility in theatre planning and more efficient use of theatre time. We recommend a dose of 40 Mbq of Tc99 m pertechnetate-labelled colloid be given day prior to surgery within a 24-hour timeframe. © 2017 The Royal Australian and New Zealand College of Radiologists.

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.

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

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.

Effectiveness and cost-effectiveness of sentinel lymph node biopsy compared with axillary node dissection in patients with early-stage breast cancer: a decision model analysis.

PubMed

Verry, H; Lord, S J; Martin, A; Gill, G; Lee, C K; Howard, K; Wetzig, N; Simes, J

2012-03-13

Sentinel lymph node biopsy (SLNB) is less invasive than axillary lymph node dissection (ALND) for staging early breast cancer, and has a lower risk of arm lymphoedema and similar rates of locoregional recurrence up to 8 years. This study estimates the longer-term effectiveness and cost-effectiveness of SLNB. A Markov decision model was developed to estimate the incremental quality-adjusted life years (QALYs) and costs of an SLNB-based staging and management strategy compared with ALND over 20 years' follow-up. The probability and quality-of-life weighting (utility) of outcomes were estimated from published data and population statistics. Costs were estimated from the perspective of the Australian health care system. The model was used to identify key factors affecting treatment decisions. The SLNB was more effective and less costly than the ALND over 20 years, with 8 QALYs gained and $883,000 saved per 1000 patients. The SLNB was less effective when: SLNB false negative (FN) rate >13%; 5-year incidence of axillary recurrence after an SLNB FN>19%; risk of an SLNB-positive result >48%; lymphoedema prevalence after ALND <14%; or lymphoedema utility decrement <0.012. The long-term advantage of SLNB over ALND was modest and sensitive to variations in key assumptions, indicating a need for reliable information on lymphoedema incidence and disutility following SLNB. In addition to awaiting longer-term trial data, risk models to better identify patients at high risk of axillary metastasis will be valuable to inform decision-making.

[Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes].

PubMed

Ruano, R; Ramos, M; García-Talavera, J R; Ramos, T; Rosero, A S; González-Orus, J M; Sancho, M

2014-01-01

To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Trends and clinicopathological predictors of axillary evaluation in ductal carcinoma in situ patients treated with breast-conserving therapy.

PubMed

Huang, Nai-Si; Si, Jing; Yang, Ben-Long; Quan, Chen-Lian; Chen, Jia-Jian; Wu, Jiong

2018-01-01

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast-conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006-2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non-evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006-2010 to 53.8% in 2011-2015 (P < 0.001), however, no patients had lymph node metastasis based on final pathology. In multivariate analysis, high-grade tumor favored axillary evaluation (OR = 4.376, 95% CI:1.410-13.586, P = 0.011); while excision biopsy favored no axillary evaluation compared with other biopsy methods (OR = 0.418, 95% CI: 0.192-0.909, P = 0.028). Subgroup analysis of patients treated in 2011-2015 revealed that high-grade tumor (OR = 5.898, 95% CI: 1.626-21.390, P = 0.007) and palpable breast lump (OR = 2.497, 95% CI: 1.037-6.011, P = 0.041) were independent predictors of axillary lymph node evaluation. Despite the significant decrease in ALND and a concerning overuse of SLNB, we identified no axillary lymph node metastasis, which justified omitting axillary evaluation in these patients. High-grade tumor, palpable lump, and biopsy method were independent predictors of axillary evaluations. Excision biopsy of suspicious DCIS lesions may potentially preclude the invasive component of the disease and help to avoid axillary surgery. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Application of carbon nanoparticles in laparoscopic sentinel lymph node detection in patients with early-stage cervical cancer.

PubMed

Lu, Yan; Wei, Jin-Ying; Yao, De-Sheng; Pan, Zhong-Mian; Yao, Yao

2017-01-01

To investigate the value of carbon nanoparticles in identifying sentinel lymph nodes in early-stage cervical cancer. From January 2014 to January 2016, 40 patients with cervical cancer stage IA2-IIA, based on the International Federation of Gynecology and Obstetrics (FIGO) 2009 criteria, were included in this study. The normal cervix around the tumor was injected with a total of 1 mL of carbon nanoparticles (CNP)at 3 and 9 o'clock. All patients then underwent laparoscopic pelvic lymph node dissection and radical hysterectomy. The black-dyed sentinel lymph nodes were removed for routine pathological examination and immunohistochemical staining. Among the 40 patients, 38 patients had at least one sentinel lymph node (SLN). The detection rate was 95% (38/40). One hundred seventy-three SLNs were detected with an average of 3.9 SLNs per side. 25 positive lymph nodes, which included 21 positive SLNs, were detected in 8 (20%) patients. Sentinel lymph nodes were localized in the obturator (47.97%), internal lilac (13.87%), external lilac (26.59%), parametrial (1.16%), and common iliac (8.67%) regions. The sensitivity of the SLN detection was 100% (5/5), the accuracy was 97.37% (37/38), and the negative predictive value was 100. 0% and the false negative rate was 0%. Sentinel lymph nodes can be used to accurately predict the pathological state of pelvic lymph nodes in early cervical cancer. The detection rates and accuracy of sentinel lymph node were high. Carbon nanoparticles can be used to trace the sentinel lymph node in early cervical cancer.

Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes.

PubMed

Wasif, Nabil; Bentrem, David J; Farrell, James J; Ko, Clifford Y; Hines, Oscar J; Reber, Howard A; Tomlinson, James S

2010-07-15

Although invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. The authors compared survival and identify prognostic factors after resection for invasive IPMN versus stage-matched PAC. The Surveillance, Epidemiology, and End Results database (1991-2005) was used to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Patients with resected invasive IPMN experienced improved overall survival when compared with resected PAC (median survival, 21 vs 14 months; P<.001). Stratification by nodal status demonstrated no difference in survival among lymph node-positive patients; however, median survival of resected, lymph node-negative, invasive IPMN was significantly improved compared with lymph node-negative PAC (34 vs 18 months; P<.001). On multivariate analysis, PAC histology was an adverse predictor of overall survival (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.50) compared with invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR, 1.98; 95% CI, 1.50-2.60), high tumor grade (HR, 1.74; 95% CI, 1.31-2.31), tumor size>2 cm (HR, 1.50; 95% CI, 1.04-2.19), and age>66 years (HR, 1.33; 95% CI, 1.03-1.73) were adverse predictors of survival. Although lymph node-negative invasive IPMN showed improved survival after resection compared with lymph node-negative PAC, the natural history of lymph node-positive invasive IPMN mimicked that of lymph node-positive PAC. The authors also identified adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis after resection of invasive IPMN. Copyright (c) 2010 American Cancer Society.

Molecular analysis of breast sentinel lymph nodes.

PubMed

Blumencranz, Peter W; Pieretti, Maura; Allen, Kathleen G; Blumencranz, Lisa E

2011-07-01

Lymphatic mapping and sentinel lymph node (SLN) biopsy have become the standard of care for staging the axilla in patients with invasive breast cancer. Current histologic methods for SLN evaluation have limitations, including subjectivity, limited sensitivity, and lack of standardization. The discovery of molecular markers to detect metastases has been reported over the last 2 decades. The authors review the historical development of these markers and the clinical use of one of the molecular platforms in 478 patients at their institution. Controversies and future directions are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Axillary web syndrome following sentinel node biopsy for breast cancer.

PubMed

Nieves Maldonado, S M; Pubul Núñez, V; Argibay Vázquez, S; Macías Cortiñas, M; Ruibal Morell, Á

2016-01-01

A 49 year-old woman diagnosed with infiltrating lobular breast carcinoma, underwent a right mastectomy and sentinel node biopsy (SLNB). The resected sentinel lymph nodes were negative for malignancy, with an axillary lymphadenectomy not being performed. In the early post-operative period, the patient reported an axillary skin tension sensation, associated with a painful palpable cord. These are typical manifestations of axillary web syndrome (AWS), a poorly known axillary surgery complication, from both invasive and conservative interventions. By presenting this case we want to focus the attention on a pathological condition, for which its incidence may be underestimated by not including it in SLNB studies. It is important for nuclear medicine physicians to be aware of AWS as a more common complication than infection, seroma, or lymphoedema, and to discuss this possible event with the patient who is consenting to the procedure. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.

Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

PubMed

Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

2013-01-01

Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

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.

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%.

Shoulder Strength Changes One Year After Axillary Lymph Node Dissection or Sentinel Lymph Node Biopsy in Patients With Breast Cancer.

PubMed

Monleon, Sandra; Ferrer, Montse; Tejero, Marta; Pont, Angels; Piqueras, Merce; Belmonte, Roser

2016-06-01

To assess the changes in shoulder strength of patients with breast cancer during the first year after surgery; and to compare the effect of sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) on shoulder strength. Prospective longitudinal observational study from presurgery to 1 year after. Tertiary hospital. Of 129 consecutive patients examined for eligibility, a sample of women (N=112) with breast cancer were included (44 underwent ALND, and 68 underwent SLNB). Not applicable. Difference between the affected and unaffected arm in strength of shoulder external rotators, internal rotators, abductors, and serratus anterior, measured by dynamometry. Evaluations were performed prior to surgery and at 1, 6, and 12 months after surgery. After breast cancer ALND surgery, strength decreased significantly at the first month for internal rotators, without having recovered presurgery values after 1 year of follow-up, with a mean difference of 2.26kg (P=.011). There was no significant loss of strength for patients treated with SLNB. The loss of shoulder range of motion was only significant the first month for the ALND group. The factors identified as associated with strength loss in the general estimating equation models were the ALND surgery and having received physical/occupational therapy during follow-up. One year after breast cancer surgery, patients treated with ALND had not recovered their previous shoulder internal rotators strength, whereas those who underwent SLNB presented no significant loss of strength. This provides important information for designing rehabilitation programs targeted specifically at the affected muscle group after nodal surgical approach. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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.

Additional Value of Diffusion-Weighted Imaging to Evaluate Prognostic Factors of Breast Cancer: Correlation with the Apparent Diffusion Coefficient.

PubMed

Park, Eun Kyung; Cho, Kyu Ran; Seo, Bo Kyoung; Woo, Ok Hee; Cho, Sung Bum; Bae, Jeoung Won

2016-01-01

Breast cancer is a heterogeneous disease with diverse prognoses. The main prognostic determinants are lymph node status, tumor size, histological grade, and biological factors, such as hormone receptors, human epidermal growth factor receptor 2 (HER2), Ki-67 protein levels, and p53 expression. Diffusion-weighted imaging (DWI) can be used to measure the apparent diffusion coefficient (ADC) that provides information related to tumor cellularity and the integrity of the cell membranes. The goal of this study was to evaluate whether ADC measurements could provide information on the prognostic factors of breast cancer. A total of 71 women with invasive breast cancer, treated consecutively, who underwent preoperative breast MRIs with DWI at 3.0 Tesla and subsequent surgery, were prospectively included in this study. Each DWI was acquired with b values of 0 and 1000 s/mm(2). The mean ADC values of the lesions were measured, including the entire lesion on the three largest sections. We performed histopathological analyses for the tumor size, lymph node status, histological grade, hormone receptors, human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and molecular subtypes. The associations with the ADC values and prognostic factors of breast cancer were evaluated using the independent-samples t test and the one-way analysis of variance (ANOVA). A low ADC value was associated with lymph node metastasis (P < 0.01) and with high Ki-67 protein levels (P = 0.03). There were no significant differences in the ADC values among the histological grade (P = 0.48), molecular subtype (P = 0.51), tumor size (P = 0.46), and p53 protein level (P = 0.62). The pre-operative use of the 3.0 Tesla DWI could provide information about the lymph node status and tumor proliferation for breast cancer patients, and could help determine the optimal treatment plan.

Correlation between obesity and prognostic/predictive parameters with emphasis on the importance of lymph node metastases in patients with invasive breast carcinoma.

PubMed

Hankó-Bauer, Orsolya; Georgescu, Rares; Coros, Marius F; Boros, Monica; Barsan, Iulia; Stolnicu, Simona

We aimed to evaluate whether obese women experience more advanced invasive breast carcinoma (IBC) with a higher number of involved lymph nodes, higher range of axillary lymph node ratio (LNR) and presence and size of extracapsular extension as it may have an impact on prognosis and management. 245 patients diagnosed with IBC were divided into normal weight (NW), overweight (OW) and obese (OB) groups. Patients were divided into high range of LNR (LNR over or equal to 0.2) and low LNR (LNR less than 0.2). The extracapsular extension dimensions were measured on the original slides of each case and grouped into ≤ 1 mm and > 1 mm. 84 patients (33.07%) were OW, 72 (29.38%) OB and 91 (37.14%) NW. 45.7% of cases had macrometastasis in the axillary lymph nodes. NW patients had significantly fewer metastatic lymph nodes (p = 0.05) than in the OW/OB groups. There was no statistically significant difference between BMI groups according to the LNR (p = 0.66). Out of 111 cases with macrometastasis, 58 cases (52.25%) had extracapsular extension (ECE) (11.7% NW, 24.32% OW and 16.22% OB). Significantly more OW patients presented extranodal invasion (p = 0.04). We found no statistically significant relationship between the extracapsular extension diameter and BMI groups (p = 0.1).

Economic evaluation of the 70-gene prognosis-signature (MammaPrint®) in hormone receptor-positive, lymph node-negative, human epidermal growth factor receptor type 2-negative early stage breast cancer in Japan.

PubMed

Kondo, Masahide; Hoshi, Shu-Ling; Ishiguro, Hiroshi; Toi, Masakazu

2012-06-01

The 70-gene prognosis-signature is validated as a good predictor of recurrence for hormone receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early stage breast cancer (ESBC) in Japanese patient population. Its high cost and potential in avoiding unnecessary adjuvant chemotherapy arouse interest in its economic impact. This study evaluates the cost-effectiveness of including the assay into Japan's social health insurance benefit package. An economic decision tree and Markov model under Japan's health system from the societal perspective is constructed with clinical evidence from the pool analysis of validation studies. One-way sensitivity analyses are also performed. Incremental cost-effectiveness ratio is estimated as ¥3,873,922/quality adjusted life year (QALY) (US$43,044/QALY), which is not more than the suggested social willingness-to-pay for one QALY gain from an innovative medical intervention in Japan, ¥5,000,000/QALY (US$55,556/QALY). However, sensitivity analyses show the instability of this estimation. The introduction of the assay into Japanese practice of ER+, LN-, HER2- ESBC treatment by including it to Japan's social health insurance benefit package has a reasonable chance to be judged as cost-effective and may be justified as an efficient deployment of finite health care resources.

Intraoperative sentinel node identification in early stage cervical cancer using a combination of radiolabeled albumin injection and isosulfan blue dye injection.

PubMed

Martínez-Palones, José M; Gil-Moreno, Antonio; Pérez-Benavente, María A; Roca, Isabel; Xercavins, Jordi

2004-03-01

We investigated the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled human serum albumin and isosulfan blue dye injection in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between September 2000 and October 2002, 25 patients with cervical cancer FIGO stage I (n=24) or stage II (n=1) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (technetium-99m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with blue dye and a handheld or laparoscopic gamma probe. Complete pelvic or paraaortic lymphadenectomy was performed in all cases by open surgery or laparoscopic surgery. In 23 evaluable patients, a total of 51 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.21 nodes per patient). Intraoperatively, 61 sentinel lymph nodes were identified, with a mean of 2.52 nodes per patient by gamma probe and a mean of 1.94 nodes per patient after isosulfan blue injection. Forty percent of sentinel nodes were found in the interiliac region and 25% in the external iliac area. Microscopic nodal metastases (four nodes) were confirmed in 12% of cases. All these lymph nodes were previously detected as sentinel lymph nodes. The remaining 419 nodes after pelvic lymphadenectomy were histologically negative. Sentinel lymph node identification with technetium-99m-labeled nanocolloid combined with blue dye injection is feasible and showed a 100% negative predictive value, and potentially identified women in whom lymph node dissection can be avoided.

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.

Morbidity after conventional dissection of axillary lymph nodes in breast cancer patients

PubMed Central

2014-01-01

Background Conventional axillary lymph node dissection (ALND) has recently become less radical. The treatment morbidity effects of reduced ALND aggressiveness are unknown. This article investigates the prevalence of the main complications of ALND: lymphedema, range-of-motion restriction, and arm paresthesia and pain. Methods This cross-sectional study included 200 women with invasive breast cancer who underwent breast-conserving surgery (82.5%, n = 165) or mastectomy (17.5%, n = 35) with ALND from 2007 to 2011. Arm perimetry was used to assess lymphedema, defined as a difference >2 cm in the upper arm circumference between the nonsurgical and surgical arms. Range-of-motion restriction was assessed by evaluating the degree of arm abduction. Paresthesia was measured in the inner and proximal arm regions. Arm pain was assessed by directly questioning the patients and defined as either present or absent. Results The average (±SD) time between ALND and morbidity evaluation was 35 ± 18 months (range, 7-60 months). The average dissected lymph node number per patient was 14 ± 4 (range, 6-30 lymph nodes). Only 3.5% (n = 7) of the patients presented with lymphedema. Single-incision approaches to breast tumor and ALND (P = 0.04) and the presence of a postoperative seroma (P = 0.02) were associated with lymphedema in univariate analysis. Paresthesia was the most frequent side effect observed (53% of patients, n = 106). This complication was associated with increased age (P < 0.0001) and a larger dissected lymph node number (P = 0.01) in univariate and multivariate analysis. Additionally, 24% (n = 48) of patients had noticeable limited arm abduction. Among the patients, 27.5% (n = 55) experienced sporadic arm pain corresponding to the surgically treated armpit. In multivariate analysis, the pain risk was 1.9-fold higher in patients who underwent ALND corresponding to their dominant arm (95% CI, 1.0-3.7, P = 0.04). Conclusion Conventional ALND in breast cancer patients can result in unwanted complications. However, the current lymphedema prevalence is lower than that of the other analyzed side effects. PMID:24670000

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.

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

Dinshaw, Ketayun A.; Budrukkar, Ashwini N.; Chinoy, Roshan F.

Purpose: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. Methods and Materials: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). Results: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women.more » The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age {<=}40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). Conclusion: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.« less

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.

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.

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.

Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.

PubMed

Lemieux, Aaron; Kedarisetty, Suraj; Raju, Sharat; Orosco, Ryan; Coffey, Charles

2016-03-01

Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Case series with chart review. Administrative database analysis. The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

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…

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.

iROLL: does 3-D radioguided occult lesion localization improve surgical management in early-stage breast cancer?

PubMed

Bluemel, Christina; Cramer, Andreas; Grossmann, Christoph; Kajdi, Georg W; Malzahn, Uwe; Lamp, Nora; Langen, Heinz-Jakob; Schmid, Jan; Buck, Andreas K; Grimminger, Hanns-Jörg; Herrmann, Ken

2015-10-01

To prospectively evaluate the feasibility of 3-D radioguided occult lesion localization (iROLL) and to compare iROLL with wire-guided localization (WGL) in patients with early-stage breast cancer undergoing breast-conserving surgery and sentinel lymph node biopsy (SLNB). WGL (standard procedure) and iROLL in combination with SLNB were performed in 31 women (mean age 65.1 ± 11.2 years) with early-stage breast cancer and clinically negative axillae. Patient comfort in respect of both methods was assessed using a ten point scale. SLNB and iROLL were guided by freehand SPECT (fhSPECT). The results of the novel 3-D image-based method were compared with those of WGL, ultrasound-based lesion localization, and histopathology. iROLL successfully detected the malignant primary and at least one sentinel lymph node in 97% of patients. In a single patient (3%), only iROLL, and not WGL, enabled lesion localization. The variability between fhSPECT and ultrasound-based depth localization of breast lesions was low (1.2 ± 1.4 mm). Clear margins were achieved in 81% of the patients; however, precise prediction of clear histopathological surgical margins was not feasible using iROLL. Patients rated iROLL as less painful than WGL with a pain score 0.8 ± 1.2 points (p < 0.01) lower than the score for iROLL. iROLL is a well-tolerated and feasible technique for localizing early-stage breast cancer in the course of breast-conserving surgery, and is a suitable replacement for WGL. As a single image-based procedure for localization of breast lesions and sentinel nodes, iROLL may improve the entire surgical procedure. However, no advantages of the image-guided procedure were found with regard to prediction of complete tumour resection.

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

Isolation of Moraxella canis from an Ulcerated Metastatic Lymph Node

PubMed Central

Vaneechoutte, Mario; Claeys, Geert; Steyaert, Sophia; De Baere, Thierry; Peleman, Renaat; Verschraegen, Gerda

2000-01-01

Moraxella canis was isolated in large numbers from an ulcerated supraclavicular lymph node of a terminal patient, who died a few days later. Although the patient presented with septic symptoms and with a heavy growth of gram-negative diplococci in the lymph node, blood cultures remained negative. M. canis is an upper-airway commensal from dogs and cats and is considered nonpathogenic for humans, although this is the third reported human isolate of this species. PMID:11015424

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer.

PubMed

Liu, Yong-Jun; Yan, Pei-Song; Li, Jun; Jia, Jing-Fen

2005-11-14

To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6, and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma, intraductal carcinoma of breast, and lung cancer. Using tissue microarray by immuhistochemical (IHC) staining and in situ hybridization (ISH), we examined the expression levels of nm23 mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6 in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer. The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P>0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P>0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P<0.01; r = -4.93, P<0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P<0.05; P<0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P<0.01; r = 5.04, P<0.01). CD44s and CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P<0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (c2 = 5.68, P<0.05). The expressional level of nm23 mRNA was closely related to the degree of cell differentiation (P<0.05) and lymph node metastasis (P<0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P>0.05). Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.

Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients.

PubMed

Lind, Guro E; Guriby, Marianne; Ahlquist, Terje; Hussain, Israr; Jeanmougin, Marine; Søreide, Kjetil; Kørner, Hartwig; Lothe, Ragnhild A; Nordgård, Oddmund

2017-01-01

Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage ( P  = 8.2E-17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P  = 3.0E-4; time to recurrence P  = 3.1E-4), although not significant. The same trend was observed in multivariate analyses ( P  = 1.4E-1 and P  = 6.7E-2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I-II) colon cancer patients who experienced relapse. Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.

Prospective Randomized Trial of Use of In-House Prepared Low-Cost Radiopharmaceutical Versus Commercial Radiopharmaceutical for Sentinel Lymph Node Biopsy in Patients with Early Stage Invasive Breast Cancer.

PubMed

Agarwal, Gaurav; Rajan, Sendhil; Mayilvaganan, Sabaretnam; Mishra, Anjali; Krishnani, Narendra; Gambhir, Sanjay

2018-05-01

The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) early breast cancers is sentinel lymph node biopsy (SLNB), which requires expensive radiopharmaceuticals for efficacious results. In-house produced low-cost radiopharmaceuticals may be the solution and have shown efficacy in earlier observational/pilot studies. We compared SLNB using in-house prepared radiopharmaceutical ( 99m Tc-Antimony-colloid) versus commercially marketed radiopharmaceutical ( 99m Tc-Sulphur-colloid) in this prospective randomized study. 78 clinically N0 early breast cancer patients (T1/2, N0 stages), undergoing primary surgery were prospectively randomized 1:1 into two groups; to receive SLNB using methylene blue, and either 99m Tc-Antimony colloid (Group-1) or   99m Tc-Sulphur colloid (Group-2). Completion axillary dissection was done in all (validation SLNB). SLNB indices were compared between the groups. The groups were comparable with regard to age, stage, tumour size, hormone receptors and HER2neu status. Cost of the in-house prepared 99m Tc-antimony colloid was 16-times lesser compared to 99m Tc-sulphur colloid. SLN identification rates (IR) in Groups 1 and 2 were 100 and 97.4% respectively, (p > 0.05). False negative rates (FNR) in Group 1 and 2 were 6.3% (1/16 patients) and 7.7% (1/13 patients), respectively, (p > 0.05). There were no major allergic reactions in either group. In this prospective randomized trial on early breast cancer patients, accuracy of SLNB was comparable using in-house prepared, 99m Tc-antimony colloid and commercially marketed 99m Tc-sulphur colloid as radiopharmaceutical, while 99m Tc-antimony colloid was much cheaper than 99m Tc-sulphur colloid.

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma

PubMed Central

Ayadi, Lobna; Khabir, Abdelmajid; Amouri, Habib; Karray, Sondes; Dammak, Abdallah; Guermazi, Mohamed; Boudawara, Tahya

2008-01-01

Background Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases. Patients and methods This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status. Results The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002). Conclusion HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER. PMID:18945339

Deviation from the Standard of Care for Early Breast Cancer in the Elderly: What are the Consequences?

PubMed

Sun, Susie X; Hollenbeak, Christopher S; Leung, Anna M

2015-08-01

For elderly patients with early-stage breast cancer, the standards of care often are not strictly followed due to either clinician biases or patient preferences. The authors hypothesized that forgoing radiation and lymph node (LN) staging for elderly patients with early-stage breast cancer would have a negative impact on survival. From the Surveillance, Epidemiology, and End Results Program database, 53,619 women older than 55 years with stage 1 breast cancer who underwent breast conservation surgery were identified. Analyses were performed to compare the characteristics and outcomes of patients who received the standards of care with LN sampling and radiation and those of patients who did not, with control used for confounders. To account for selection bias from covariate imbalance, propensity score matching was performed. Survival was analyzed using the Kaplan-Meier method. Older patients were less likely to receive radiation and LN sampling. These standards of care were associated with improved overall survival rates of 15.8 and 27.1 % after 10 years, respectively (p ≤ 0.0001). This survival advantage persisted after propensity score matching, with a 7.4 % higher survival rate for patients who received radiation and a 16.8 % higher survival rate for those who underwent LN staging (p < 0.0001). Lymph node sampling and radiation therapy also conferred a statistically significant improvement in breast cancer-specific survival, with 1.3 and 2.6 % lower mortality rates respectively in the radiated and LN biopsy groups (p < 0.0001). As patients age, they are less likely to receive the standard of care for stage 1 breast cancer. Even after controlling for other factors, the study showed that failure to adhere to the standards of LN sampling and radiation therapy may have a negative impact in survival.

A Novel Color Fluorescence Navigation System for Intraoperative Transcutaneous Lymphatic Mapping and Resection of Sentinel Lymph Nodes in Breast Cancer: Comparison with the Combination of Gamma Probe Scanning and Visible Dye Methods.

PubMed

Hokimoto, Norihiro; Sugimoto, Takeki; Namikawa, Tsutomu; Funakoshi, Taku; Oki, Toyokazu; Ogawa, Maho; Fukuhara, Hideo; Inoue, Keiji; Sato, Takayuki; Hanazaki, Kazuhiro

2018-01-01

This study evaluated the clinical efficacy of a novel imaging system (HyperEye Medical System [HEMS]; Mizuho Corp., Tokyo, Japan) that uses the near-infrared (NIR) fluorescence of indocyanine green to analyze sentinel lymph node (SLN) biopsies for the staging of breast cancer. This study enrolled 91 patients with histologically confirmed breast cancer that was clinically node negative with a tumor size <3 cm. We compared SLN identification rates between HEMS and conventional methods (gamma probe scanning using a colloidal radioisotope [RI] and a blue dye method) by analyzing the relationships of lymphatic to axillary lesions and SLNs. The identification rate of SLNs was 100% using HEMS, 97.8% using the RI method, and 95.6% using the blue dye method. Two types of lymphatic pathway (LP) were detected in 39 patients (42.9%) and also clearly identified using HEMS-captured color and NIR fluorescence. The incidence of two or more SLNs was significantly higher in patients with a two-route LP to the axilla group than in those with only one route (p < 0.001; 43.6 vs. 9.6%). The HEMS NIR fluorescence color imaging method is a promising potential modality for higher-level identification of SLNs than a standard combination of the RI and blue dye methods. © 2017 S. Karger AG, Basel.

Correlation between obesity and fat-infiltrated axillary lymph nodes visualized on mammography.

PubMed

diFlorio Alexander, Roberta M; Haider, Steffen J; MacKenzie, Todd; Goodrich, Martha E; Weiss, Julie; Onega, Tracy

2018-01-05

Using screening mammography, this study investigated the association between obesity and axillary lymph node (LN) size and morphology. We conducted a retrospective review of 188 females who underwent screening mammography at an academic medical centre. Length and width of the LN and hilum were measured in the largest, mammographically visible axillary node. The hilo-cortical ratio (HCR) was calculated as the hilar width divided by the cortical width. Measurements were performed by a board certified breast radiologist and a resident radiology physician. Inter-rater agreement was assessed with Pearson correlation coefficient. We performed multivariable regression analysis for associations of LN measurements with body mass index (BMI), breast density and age. There was a strong association between BMI and LN dimensions, hilum dimensions and HCR (p < 0.001 for all metrics). There was no significant change in cortex width with increasing BMI (p = 0.15). Increases in LN length and width were found with increasing BMI [0.6 mm increase in length per unit BMI, 95% CI (0.4-0.8), p < 0.001 and0.3 mm increase in width per unit BMI, 95% CI(0.2-0.4), p < 0.001, respectively]. Inter-rater reliability for lymph node and hilum measurements was 0.57-0.72. We found a highly significant association between increasing BMI and axillary LN dimensions independent of age and breast density with strong interobserver agreement. The increase in LN size was driven by expansion of the LN hilum secondary to fat infiltration. Advances in knowledge: This preliminary work determined a relationship between fat infiltrated axillary lymph nodes and obesity.

Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure

PubMed Central

Peck, Amy R.; Witkiewicz, Agnieszka K.; Liu, Chengbao; Stringer, Ginger A.; Klimowicz, Alexander C.; Pequignot, Edward; Freydin, Boris; Tran, Thai H.; Yang, Ning; Rosenberg, Anne L.; Hooke, Jeffrey A.; Kovatich, Albert J.; Nevalainen, Marja T.; Shriver, Craig D.; Hyslop, Terry; Sauter, Guido; Rimm, David L.; Magliocco, Anthony M.; Rui, Hallgeir

2011-01-01

Purpose To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. Patients and Methods Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. Results Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). Conclusion Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy. PMID:21576635

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.

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.

A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study.

PubMed

Rossi, Emma C; Kowalski, Lynn D; Scalici, Jennifer; Cantrell, Leigh; Schuler, Kevin; Hanna, Rabbie K; Method, Michael; Ade, Melissa; Ivanova, Anastasia; Boggess, John F

2017-03-01

Sentinel-lymph-node mapping has been advocated as an alternative staging technique for endometrial cancer. The aim of this study was to measure the sensitivity and negative predictive value of sentinel-lymph-node mapping compared with the gold standard of complete lymphadenectomy in detecting metastatic disease for endometrial cancer. In the FIRES multicentre, prospective, cohort study patients with clinical stage 1 endometrial cancer of all histologies and grades undergoing robotic staging were eligible for study inclusion. Patients received a standardised cervical injection of indocyanine green and sentinel-lymph-node mapping followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy. 18 surgeons from ten centres (tertiary academic and community non-academic) in the USA participated in the trial. Negative sentinel lymph nodes (by haematoxylin and eosin staining on sections) were ultra-staged with immunohistochemistry for cytokeratin. The primary endpoint, sensitivity of the sentinel-lymph-node-based detection of metastatic disease, was defined as the proportion of patients with node-positive disease with successful sentinel-lymph-node mapping who had metastatic disease correctly identified in the sentinel lymph node. Patients who had mapping of at least one sentinel lymph node were included in the primary analysis (per protocol). All patients who received study intervention (injection of dye), regardless of mapping result, were included as part of the assessment of mapping and in the safety analysis in an intention-to-treat manner. The trial was registered with ClinicalTrials.gov, number NCT01673022 and is completed and closed. Between Aug 1, 2012, and Oct 20, 2015, 385 patients were enrolled. Sentinel-lymph-node mapping with complete pelvic lymphadenectomy was done in 340 patients and para-aortic lymphadenectomy was done in 196 (58%) of these patients. 293 (86%) patients had successful mapping of at least one sentinel lymph node. 41 (12%) patients had positive nodes, 36 of whom had at least one mapped sentinel lymph node. Nodal metastases were identified in the sentinel lymph nodes of 35 (97%) of these 36 patients, yielding a sensitivity to detect node-positive disease of 97·2% (95% CI 85·0-100), and a negative predictive value of 99·6% (97·9-100). The most common grade 3-4 adverse events or serious adverse events were postoperative neurological disorders (4 patients) and postoperative respiratory distress or failure (4 patients). 22 patients had serious adverse events, with one related to the study intervention: a ureteral injury incurred during sentinel-lymph-node dissection. Sentinel lymph nodes identified with indocyanine green have a high degree of diagnostic accuracy in detecting endometrial cancer metastases and can safely replace lymphadenectomy in the staging of endometrial cancer. Sentinel lymph node biopsy will not identify metastases in 3% of patients with node-positive disease, but has the potential to expose fewer patients to the morbidity of a complete lymphadenectomy. Indiana University Health, Indiana University Health Simon Cancer Center, and the Indiana University Department of Obstetrics and Gynecology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spectral imaging as a potential tool for optical sentinel lymph node biopsies

NASA Astrophysics Data System (ADS)

O'Sullivan, Jack D.; Hoy, Paul R.; Rutt, Harvey N.

2011-07-01

Sentinel Lymph Node Biopsy (SLNB) is an increasingly standard procedure to help oncologists accurately stage cancers. It is performed as an alternative to full axillary lymph node dissection in breast cancer patients, reducing the risk of longterm health problems associated with lymph node removal. Intraoperative analysis is currently performed using touchprint cytology, which can introduce significant delay into the procedure. Spectral imaging is forming a multi-plane image where reflected intensities from a number of spectral bands are recorded at each pixel in the spatial plane. We investigate the possibility of using spectral imaging to assess sentinel lymph nodes of breast cancer patients with a view to eventually developing an optical technique that could significantly reduce the time required to perform this procedure. We investigate previously reported spectra of normal and metastatic tissue in the visible and near infrared region, using them as the basis of dummy spectral images. We analyse these images using the spectral angle map (SAM), a tool routinely used in other fields where spectral imaging is prevalent. We simulate random noise in these images in order to determine whether the SAM can discriminate between normal and metastatic pixels as the quality of the images deteriorates. We show that even in cases where noise levels are up to 20% of the maximum signal, the spectral angle map can distinguish healthy pixels from metastatic. We believe that this makes spectral imaging a good candidate for further study in the development of an optical SLNB.

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.

microRNA-200c/141 upregulates SerpinB2 to promote breast cancer cell metastasis and reduce patient survival.

PubMed

Jin, Tiefeng; Suk Kim, Hoe; Ki Choi, Sul; Hye Hwang, Eun; Woo, Jisu; Suk Ryu, Han; Kim, Kwangsoo; Moon, Aree; Kyung Moon, Woo

2017-05-16

The microRNA-200 (miR-200) family is associated with tumor metastasis and poor patient prognosis. We found that miR-200c/141 cluster overexpression upregulated SerpinB2 in the MDA-MB-231 triple-negative (TN) breast cancer cell line. We observed transcription factor (c-Jun, c-Fos, and FosB) upregulation, nuclear localization of c-Jun, and increased SerpinB2 promoter-directed chloramphenicol acetyltransferase activity in miR-200c/141 cluster-overexpressing cells relative to controls. Additionally, miR-124a and miR-26b, which directly target SepinB2, were downregulated compared to controls. In mouse xenograft models, miR-200c/141 cluster overexpression promoted lymph node and lung metastasis, and siRNA-mediated SerpinB2 knockdown decreased lung metastasis, suggesting that SerpinB2 mediates miR-200c/141-induced lung metastasis. We also explored the clinical significance of SerpinB2 protein status through analysis of primary breast tumor samples and The Cancer Genome Atlas (TCGA) data. High SerpinB2 levels were associated with reduced survival and increased lymph node metastasis in breast cancer patients. SerpinB2 was overexpressed in the TN breast cancer subtype as compared to the luminal subtype. The present study demonstrates that SerpinB2 promotes miR-200c/141 cluster overexpression-induced breast cancer cell metastasis, and SerpinB2 overexpression correlates with increased metastatic potential and unfavorable outcomes in breast cancer patients. SerpinB2 may be a useful biomarker for assessing metastasis risk in breast cancer patients.

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

Ductal carcinoma in situ diagnosed using an ultrasound-guided 14-gauge core needle biopsy of breast masses: can underestimation be predicted preoperatively?

PubMed Central

2014-01-01

Purpose: This study was designed to determine the rate of ductal carcinoma in situ (DCIS)underestimation diagnosed after an ultrasound-guided 14-gauge core needle biopsy (US-14G-CNB) of breast masses and to compare the clinical and imaging characteristics between trueDCIS and underestimated DCIS identified following surgical excision. Methods: Among 3,124 US-14G-CNBs performed for breast masses, 69 lesions in 60 patients were pathologically-determined to be pure DCIS. We classified these patients according to the final pathology after surgical excision as those with invasive ductal carcinoma (underestimated group) and those with DCIS (non-underestimated group). We retrospectively reviewed and compared the clinical and imaging characteristics between the two groups. Results: Of the 69 lesions, 21 were shown after surgery to be invasive carcinomas; the rateof DCIS underestimation was 30.4%. There were no statistically significant differences withrespect to the clinical symptoms, age, lesion size, mammographic findings, and ultrasonographic findings except for the presence of abnormal axillary lymph nodes as detected on ultrasound. The lesions in 2 patients in the non-underestimated group (2/41, 4.9%) and 5 patients in the underestimated group (5/19, 26.3%) were associated with abnormal lymph nodes on axillary ultrasound, and the presence of abnormal axillary lymph nodes on ultrasound was tatistically significant (P=0.016). Conclusion: We found a 30.4% rate of DCIS underestimation in breast masses based on a US-14G-CNB. The presence of abnormal lymph nodes as detected on axillary ultrasound may be useful to preoperatively predict underestimation. PMID:24936506

Shoulder-arm morbidity in patients with sentinel node biopsy and complete axillary dissection--data from a prospective randomised trial.

PubMed

Helms, G; Kühn, T; Moser, L; Remmel, E; Kreienberg, R

2009-07-01

Axillary lymph node dissection (ALND) as part of surgical treatment in breast cancer has been the standard procedure for many decades. However, patients frequently develop shoulder-arm morbidity postoperatively. Recently, sentinel node (SN) biopsy has been established as a new standard of care for axillary staging in breast cancer. This study compares postoperative morbidity between ALND and SN biopsy. The results are compared with the existing literature. Between November 2000 and September 2002, 181 women with early stage breast cancer underwent primary surgery following preoperative randomisation into two groups, a "standard group" (SN biopsy was followed by ALND) and a study group (surgical procedure consisting of only SN biopsy when histologically metastasis-free SN was present). Follow-up data (362 sessions; 6 months to 3 years after primary surgery) were available from 150 patients. A summary morbidity score was calculated from four subjective (arm-strength, arm-mobility, arm swelling, pain) and four objective (arm-strength, arm-mobility, lymphedema, sensitivity) criteria. Fifty seven patients underwent SN biopsy only. Ninety three patients underwent ALND, 57 of which had lymph nodes free of metastasis and 36 had lymph nodes with metastasis and axillary clearing. Shoulder-arm morbidity was significantly different between the groups. Patients treated with SN biopsy only scored better on subjective and objective criteria. Postsurgical shoulder-arm morbidity is a major long-term problem in patients undergoing surgical treatment for breast cancer. This prospective study showed significantly less severe shoulder-arm morbidity following SN biopsy compared to patients undergoing ALND.

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.

Sentinel lymph node biopsy in periocular merkel cell carcinoma: a case report.

PubMed

Filitis, Dan C; Paragh, Gyorgy; Samie, Faramarz H; Zeitouni, Nathalie C

2017-09-20

The National Comprehensive Cancer Network guidelines for Merkel cell carcinoma recommend performance of the sentinel lymph node biopsy in all patients with clinically negative nodal disease for staging and treatment. Nevertheless, sentinel lymph node biopsy in the periocular region is debated as tumors are typically smaller and lymphatic variability can make performance procedurally problematic. We present a case of a Caucasian patient in their seventies who presented with a 1.0 cm periocular Merkel cell carcinoma, who underwent Mohs surgery with a Tenzel flap repair, that was found to have a positive sentinel lymph node biopsy, but who, despite parotidectomy, selective neck dissection, and radiation, succumbed to the disease. Evidence in both the site-specific and non-specific literature demonstrates: (1) Worsening prognosis with extent of lymph node burden, (2) improvements in our abilities to perform lymphoscintigraphy, (3) locoregional and distant metastatic disease in patients with tumor sizes ≤1 cm, and (4) significant rates of sentinel lymph node positivity in patients with tumor sizes ≤1 cm. Our case supports that sentinel lymph node biopsy should be considered in all clinically nodal negative periocular Merkel cell carcinoma, regardless of size, and despite limited site-specific studies on the subject.

Extent of surgery for papillary thyroid cancer: preoperative imaging and role of prophylactic and therapeutic neck dissection.

PubMed

Cisco, Robin M; Shen, Wen T; Gosnell, Jessica E

2012-03-01

Papillary thyroid cancer (PTC) has an excellent prognosis, yet lymph node metastases are common. Most authors agree that central and/or lateral lymph node dissection should be undertaken in patients with abnormal lymph nodes detected on ultrasound, physical examination or intraoperative inspection. However the appropriate extent of prophylactic lymph node dissection for clinically node-negative patients remains the subject of controversy. There have been no randomized trials to date to offer guidance on this issue. The 2006 guidelines of the American Thyroid Association recommended consideration of prophylactic bilateral central lymph node dissection (CLND) for all patients undergoing thyroidectomy for PTC. However, the absence of compelling evidence for a benefit in terms of recurrence or survival, and the potential for increased morbidity, have led many, including our institution, to take an approach of selective central lymph node dissection. This approach is guided by the detection of abnormal lymph nodes on preoperative ultrasound, on physical examination, or during surgery. Postoperatively, ultrasound by an experienced ultrasonographer is the mainstay of evaluation for lymph node recurrence and is combined with monitoring of thyroglobulin and antithyroglobulin antibody levels. Reoperative lymph node dissection is typically undertaken upon detection and fine needle aspiration (FNA) of involved lymph nodes 0.8 cm or greater in size.

Recurrence and 5-FU sensitivity of stage I/II node-negative breast, lung, or gastric cancer with occult neoplastic cells in lymph node sinuses.

PubMed

Mukai, Masaya; Sato, Shinkichi; Tajima, Takayuki; Ninomiya, Hiromi; Wakui, Kanako; Komatsu, Nobukazu; Tsuchiya, Kazutoshi; Nakasaki, Hisao; Makuuchi, Hiroyasu

2006-04-01

This study was designed to examine the relationship between the presence of occult neoplastic cells (ONCs) in lymph nodes (LNs) and survival in 238 patients with stage I/II LN-negative cancer of the breast, lung, or stomach. In addition, immunohistochemistry for TS and DPD was used to compare the 5-FU sensitivity of the primary tumor in ONC (+) patients. The 5-year relapse-free survival (RFS) rate of 215 ONC (-) patients and 23 ONC (+) patients was 95.2 and 82.6%, respectively (p=0.0107). The 5-year overall survival (OS) rate of the ONC (-) and (+) patients was 97.4 and 77.4%, respectively (p=0.0000). The 6 ONC (+) patients with recurrence showed high and low TS expression in 33.3% (2/6) and 66.7% (4/6), respectively, while high and low DPD expression was observed in 16.7% (1/6) and 83.3% (5/6), respectively. In the 17 ONC (+) patients without recurrence, the corresponding values were 64.7% (11/17), 35.3% (6/17), 29.4% (5/17), and 70.6% (12/17). Patients with a combination of high TS and low DPD expression accounted for 33.3% (2/6) of the ONC (+) patients with recurrence and 52.9% (9/17) of those without recurrence, showing no significant difference between the two groups. These results suggest that ONCs are associated with a lower survival rate and that ONC (+) patients are unlikely to respond to 5-FU+LV therapy.

Irregular echogenic foci representing coagulation necrosis: a useful but perhaps under-recognized EUS echo feature of malignant lymph node invasion.

PubMed

Bhutani, Manoop S; Saftoiu, Adrian; Chaya, Charles; Gupta, Parantap; Markowitz, Avi B; Willis, Maurice; Kessel, Ivan; Sharma, Gulshan; Zwischenberger, Joseph B

2009-06-01

Coagulation necrosis has been described in malignant lymph nodes. Our aim was to determine if coagulation necrosis in mediastinal lymph nodes imaged by EUS could be used as a useful echo feature for predicting malignant invasion. Patients with known or suspected lung cancer who had undergone mediastinal lymph node staging by EUS. Tertiary Care university hospital. An expert endosonographer blinded to the final diagnosis, reviewed the archived digital EUS images of lymph nodes prior to being sampled by FNA. LNs positive for malignancy by FNA were included. The benign group included lymph node images with either negative EUS-FNA or lymph nodes imaged by EUS but not subjected to EUS-FNA, with surgical correlation of their benign nature. 24 patients were included. 8 patients were found to have coagulation necrosis. 7/8 patients had positive result for malignancy by EUS-FNA. One patient determined to have coagulation necrosis had a non-malignant diagnosis indicating a false positive result. 16 patients had no coagulation necrosis. In 6 patients with no coagulation necrosis, the final diagnosis was malignant and in the remaining 10 cases, the final diagnosis was benign. For coagulation necrosis as an echo feature for malignant invasion, sensitivity was 54%, specificity was 91%, positive predictive value was 88%, negative predictive value was 63% and accuracy was 71%. Coagulation necrosis is a useful echo feature for mediastinal lymph node staging by EUS.

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

Prognostic significance of number of nodes removed in patients with node-negative early cervical cancer.

PubMed

Mao, Siyue; Dong, Jun; Li, Sheng; Wang, Yiqi; Wu, Peihong

2016-10-01

The aim of this study was to investigate whether the number of removed lymph nodes was associated with survival of patients with node-negative early cervical cancer and to analyze the prognostic significance of clinical and pathologic features in these patients. Patients with FIGO stage IA-IIB cervical cancer who underwent radical hysterectomy with lymphadenectomy without receiving preoperative therapy were reviewed retrospectively. Patients were all proved to have lymph-node-negative disease and classified into five groups based on the number of nodes removed. The Kaplan-Meier method and Cox's proportional hazards regression model were used in prognostic analysis. The final dataset included 359 patients: 45 (12.5%) patients had ≤10 nodes removed, 93 (25.9%) had 11-15, 98 (27.3%) had 16-20, 64 (17.8%) had 21-25, and 59 (16.4%) had >25 nodes removed. There was no association between the number of nodes removed and survival of patients with node-negative early cervical cancer (χ 2  = 6.19, P = 0.185). Similarly, subgroup analyses for FIGO stage IB1-IIB also showed that the number of lymph nodes was not significantly related to survival in each stage. Multivariate analyses showed that histology and depth of invasion were independent prognostic factors for survival in these patients. If a standardized lymphadenectomy is performed, the number of lymph nodes removed is not an independent prognostic factor for patients with node-negative early cervical cancer. Our study suggests that there is inconclusive evidence to support survival benefit of complete lymphadenectomy among these patients. © 2016 Japan Society of Obstetrics and Gynecology.

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

Breast Cancer: subgroups specific blood-biomarkers for early / predictive diagnosis and personalized treatment — EDRN Public Portal

Cancer.gov

Breast-conserving lumpectomy followed by radiation therapy has been shown to be an alternative strategy, competitive to mastectomy, in preventing mortality caused by breast cancer. However, besides negative short-term effects (blood flow disturbances, painful erythema, etc.) breast irradiation causes severe long-term side-effects (leucopenia, anemia, breast edema, fibrosis, increase of angiosarcoma, leukemia, myelodysplastic syndromes). Therefore, the identification of individual susceptibility to radiation and improved patient-specific radiotherapy planning are highly desirable for personalised treatment in breast cancer. Why early and predictive diagnosis is crucial for long-term outcomes of breast cancer? Breast cancer is the most common cause of cancer death among women with an average incidence rate of 10-12 per 100 women. In 2005, breast cancer led to 502,000 deaths worldwide. Advanced stages of breast cancer lead to the development of metastasis predominantly in the lymph nodes, bone, lung, skin, brain, and liver. Although breast-MRI is currently the most sensitive diagnostic tool for breast imaging, its specificity is limited resulting in a negative impact for surgical management in approximately 9 % of cases. Early diagnosis has been demonstrated to be highly beneficial, enabling significantly enhanced therapy efficiency and possibly full recovery.

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.

Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol☆

PubMed Central

Wallace, Anne M.; Hoh, Carl K.; Limmer, Karl K.; Darrah, Denise D.; Schulteis, Gery; Vera, David R.

2014-01-01

Lymphoseek is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node (SLN) mapping. We conducted a clinical trial which measured the injection site clearance and sentinel lymph node accumulation after a single intradermal injection of Lymphoseek or unfiltered [99mTc]sulfur colloid (TcSC) using a “2-day” protocol for SLN mapping of breast cancer. Eleven patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of 99mTc-labeled Lymphoseek; SLN mapping was performed on four subjects within 19 to 27 h. Six subjects received an intradermal administration of TcSC; SLN mapping was performed on five subjects within 18 to 26 h. Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than TcSC. The mean Lymphoseek clearance half-time was 2.18±1.09 h compared to 57.4±92.8 h for TcSC. The mean sentinel lymph node uptake of Lymphoseek (1.5±1.7%) and TcSC (3.5±3.1%) was statistically equivalent (P=.213). When an intradermal injection is employed, Lymphoseek demonstrated faster injection site clearance than unfiltered [99mTc]sulfur colloid and persistent SLN accumulation for at least 24 h. PMID:19647175

Comparison of 2- and 4-wavelength methods for the optical detection of sentinel lymph node

NASA Astrophysics Data System (ADS)

Tellier, F.; Simon, H.; Blé, F. X.; Ravelo, R.; Chabrier, R.; Steibel, J.; Rodier, J. F.; Poulet, P.

2011-07-01

Sentinel lymph node biopsy is the gold standard method to detect a metastatic invasion from the primary breast cancer. This method can avoid patients to be submitted to full axillary chain dissection. In this study we present and compare two near-infrared optical probes for the sentinel lymph node detection, based on the recording of scattered photons. The two setups were developed to improve the detection of the dye injected in clinical routine: the Patent Blue V dye. Herein, we present results regarding clinical ex-vivo detection of sentinel lymph node after different volume injections. We have previously published results obtained with a two-wavelength probe on phantom and animal models. However this first generation device did not completely account for the optical absorption variations from biological tissue. Thus, a second generation probe has been equipped with four wavelengths. The dye concentration computation is then more robust to measurement and tissue property fluctuations. The detection threshold of the second setup was estimated at 8.10-3μmol/L, which is about 37 times lower than the eye visibility threshold. We present here the preliminary results and demonstrate the advantages of using four wavelengths compared to two on phantom suspensions simulating the optical properties of breast tissues.

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

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.

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.

Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study.

PubMed

Wang, Xuejuan; Yang, Zhi; Lin, Baohe; Zhang, Yan; Zhai, Shizhen; Zhao, Qichao; Xie, Qing; Liu, Fei; Han, Xuedi; Li, Jinfeng; Ouyang, Tao

2016-06-21

We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection. 99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection. The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively. 99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.

Sentinel lymph node biopsy in cutaneous melanoma of the head and neck using the indocyanine green SPY Elite system.

PubMed

Vahabzadeh-Hagh, Andrew M; Blackwell, Keith E; Abemayor, Elliot; St John, Maie A

2018-05-17

Lymph node status is the single most important prognostic factor for patients with early-stage cutaneous melanoma. Sentinel lymph node biopsy (SLNB) has become the standard of care for intermediate depth melanomas. Modern SLNB implementation includes technetium-99 lymphoscintigraphy combined with local administration of a vital blue dye. However, sentinel lymph nodes may fail to localize in some cases and false-negative rates range from 0 to 34%. Here we demonstrate the feasibility of a new sentinel lymph node biopsy technique using indocyanine green (ICG) and the SPY Elite near-infrared imaging system. Cases of primary cutaneous melanoma of the head and neck without locoregional metastasis, underwent SLNB at a single quaternary care institution between May 2016 and June 2017. Intraoperatively, 0.25 mL of ICG was injected intradermal in 4 quadrants around the primary lesion. 10-15 minute circulation time was permitted. SPY Elite identified the sentinel lymph node within the nodal basin marked by lymphoscintigraphy. Target first echelon lymph nodes were confirmed with a gamma probe and ICG fluorescence. 14 patients were included with T1a to T4b cutaneous melanomas. Success rates for sentinel lymph node identification using lymphoscintigraphy and the SPY Elite system were both 86%. Zero false negatives occurred. Median length of follow-up was 323 days. In this pilot study, Indocyanine green near-infrared fluorescence demonstrates a safe, and facile method of sentinel lymph node biopsy for cutaneous melanoma of the head and neck compared with lymphoscintigraphy and vital blue dyes. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

[Characteristics of regional lymph nodes in breast cancer (quantitative histochemical study)].

PubMed

Anisimova, L O

1982-01-01

The changes in axillary lymph nodes in mammary gland carcinoma of different histological types, metastasizing and nonmetastasizing, as well as after radiation therapy and in fibroadenomatosis were studied. The study was carried out on cryostate sections by histological and histochemical methods. Signs of activation of lymph nodes were clearly seen only in solid carcinoma, not always manifested in adenocarcinomas and scirrhous carcinomas, and undetectable in fibroadenomatosis. The quantitative determination of enzymes and nucleic acids showed differences in their activity between fibroadenomatosis and carcinomas. Proliferation processes dominated significantly over lymphocyte differentiation in carcinoma, increasing even more in metastasizing tumors. Pre-operative irradiation did not inhibit metabolism or proliferative activity of the cells.

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

PubMed

Lee, Young Chan; Na, Se Young; Park, Gi Cheol; Han, Ju Hyun; Kim, Seung Woo; Eun, Young Gyu

2017-02-01

The impact of occult lymph node metastasis on regional recurrence after prophylactic central neck dissection for preoperative, nodal-negative papillary thyroid cancer is controversial. We investigated risk factors for regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Analysis was according to clinicopathologic characteristics and occult lymph node metastasis patterns. This multicenter study enrolled 211 consecutive patients who underwent total thyroidectomy with bilateral prophylactic central neck dissection for papillary thyroid cancer without evidence of central lymph node metastasis on preoperative imaging. Clinicopathologic features and central lymph node metastasis patterns were analyzed for predicting regional recurrence. Multivariate Cox regression analysis was used to identify independent factors for recurrence. Median follow-up time was 43 months (24-95 months). Ten patients (4.7%) showed regional lymph node recurrence. The estimated 5-year, regional recurrence-free survival was 95.2%. Tumor size ≥1 cm, central lymph node metastasis, lymph node ratio, and prelaryngeal lymph node metastasis were associated with regional recurrence in univariate analysis (P < .05). In multivariate analysis, a lymph node ratio ≥ 0.26 was a significant risk factor for regional lymph node recurrence (odds ratio = 11.63, P = .003). Lymph node ratio ≥ 0.26 was an independent predictor of worse recurrence-free survival on Cox regression analysis (hazard ratio = 11.49, P = .002). Although no significant association was observed between the presence of occult lymph node metastasis and regional recurrence, lymph node ratio ≥ 0.26 was an independent predictor of regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinicopathological significance of plasminogen activator inhibitor-1 promoter 4G/5G polymorphism in breast cancer: a meta-analysis.

PubMed

Lee, Ju-Han; Kim, Younghye; Choi, Jung-Woo; Kim, Young-Sik

2013-01-01

Plasminogen activator inhibitor type 1 (PAI-1) is associated with poor prognosis in breast cancer. Transcriptional expression of the PAI-1 can be controlled by PAI-1 promoter 4G/5G polymorphism. However, the significance of PAI-1 promoter 4G/5G polymorphism in breast cancer patients is contentious. To address this controversy, we conducted a meta-analysis for the relationships between PAI-1 promoter polymorphism and clinicopathological characteristics of breast cancer. Relevant published studies were identified using a search of PubMed, Embase, and the ISI Web of Science. The effect sizes of PAI-1 promoter 4G/5G polymorphism on breast cancer risk, lymph node metastasis, histologic grade, and overall survival were calculated by odds ratio (OR) or hazard ratio. The effect sizes were combined using a random-effects model. Individuals with 4G/4G genotype had a higher risk of breast cancer than those with the combined 4G/5G and 5G/5G genotypes (OR = 1.388; p = 0.031). Breast cancer patients with the 5G/5G genotype displayed lymph node metastasis more than patients with either the combined other genotypes (OR = 1.495; p = 0.027) or with the 4G/4G genotype (OR = 1.623; p = 0.018). However, the PAI-1 promoter 4G/5G polymorphism was not associated with histological grade or overall survival. PAI-1 promoter 4G/5G polymorphism is associated with a relatively increased risk of breast cancer development and lymph node metastasis. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Silicone granuloma from ruptured breast implants as a cause of cervical lymphadenopathy

PubMed Central

Gallagher, G; Skelly, BL

2016-01-01

A 56-year-old woman with a 10-year history of bilateral silicone breast implants presented to the ear, nose and throat outpatient clinic with a 2-month history of a right-sided neck lump. She was found to have a 1.3cm supraclavicular lymph node that gave the clinical impression of being reactive. Ultrasonography guided fine needle aspiration was inconclusive and initial review of subsequent computed tomography failed to identify a cause. This was followed by excisional biopsy of the lymph node, which revealed a silicone granuloma that was linked to a ruptured right-sided breast implant placed ten years previously. This case highlights the importance for otolaryngologists to consider silicone granuloma among the differential diagnoses of cervical lymphadenopathy in patients with a history of silicone breast implants. Recognising this differential diagnosis could avoid undue anxiety for patient and clinician regarding more serious pathology. PMID:27167311

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

[Identification of cervical lymph node micrometastasis of tongue cancer by color Doppler and MRI].

PubMed

Fan, Sufeng; Zhang, Quan; Li, Qiuli; Wang, Lina; Zheng, Lie; Liu, Longzhong

2014-01-01

To assess the values of color Doppler and magnetic resonance imaging (MRI) in the identification of cervical lymph node micrometastasis of tongue cancer. Totally 96 cases of tongue cancer with impalpable neck lymph node was examined with color Doppler and MRI within one week before surgery. Chi-square test was used to assess if the presence of regional lymph node micrometastasis, histopathological analysis as a golden standard lymph node micrometastasis. For the diagnosis of cervical lymph node micrometastasis, color Doppler was significantly better than MRI in sensitivity (72.5% vs 50.0%, P = 0.039) and the accuracy (78.1% vs 64.6%, P = 0.038), but no significant difference in the specificity (82.1% vs 75.0%, P = 0.357), the positive predictive value (74.4% vs 58.8%, P = 0.159) and the negative predictive value (80.7% vs 67.7%, P = 0.108). Color Doppler is better than MRI in the sensitivity and accuracy for the diagnosis of cervical lymph node micrometastasis of tongue cancer.

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.

A prospective randomized trial comparing patent blue and methylene blue for the detection of the sentinel lymph node in breast cancer patients.

PubMed

Paulinelli, Régis Resende; Freitas-Junior, Ruffo; Rahal, Rosemar Macedo de Souza; Oliveira, Luis Fernando de Pádua; Vilela, Maria Helena Tavares; Moreira, Marise Amaral Rebouças; Alves, Katyane Larissa; Peleja, Marina Berquó; Resende, Tatiane Coelho Capel de

2017-02-01

Methylene blue is more widely available and less expensive than patent blue, with an apparently lower risk of anaphylaxis. The two dyes were compared regarding detection of the sentinel lymph node (SLN). A prospective, randomized trial involved 142 patients with invasive breast carcinoma. Sixty-nine (49.3%) assigned to patent blue (group A) and 71 (50.70%) to methylene blue (group B). Thirty-five patients (25.0%) were clinical stage III or IV; 55 (38.7%) had axillary lymph nodes affected; and 69 (49.3%) underwent neoadjuvant chemotherapy. Two patients were excluded because the dye type was not recorded. Patients and tumor characteristics were similar in both groups. SLNs were identified in 47 women (68.1%) in group A and 43 (60.6%) in group B (p=0.35). SLNs were affected in 22 cases (51.2%) in group A and 21 (48.8%) in group B (p=0.62). The SLN was the only node affected in 12 cases (54.5%) in group A and six (33.3%) in group B (p=0.18). The time and degree of difficulty involved in identifying the SLN were similar in both groups. There were no complications or allergies. Methylene blue performed as well as patent blue in identifying the SLN in breast cancer patients.

Predicted extracapsular invasion of hilar lymph node metastasis by fusion positron emission tomography/computed tomography in patients with lung cancer

PubMed Central

MAKINO, TAKASHI; HATA, YOSHINOBU; OTSUKA, HAJIME; KOEZUKA, SATOSHI; ISOBE, KAZUTOSHI; TOCHIGI, NOBUMI; SHIRAGA, NOBUYUKI; SHIBUYA, KAZUTOSHI; HOMMA, SAKAE; IYODA, AKIRA

2015-01-01

Intraoperative detection of hilar lymph node metastasis, particularly with extracapsular invasion, may affect the surgical procedure in patients with lung cancer, as the preoperative estimation of hilar lymph node metastasis is unsatisfactory. The aim of this study was to investigate whether fusion positron emission tomography/computed tomography (PET/CT) is able to predict extracapsular invasion of hilar lymph node metastasis. Between April, 2007 and April, 2013, 509 patients with primary lung cancer underwent surgical resection at our institution, among whom 28 patients exhibiting hilar lymph node metastasis (at stations 10 and 11) were enrolled in this study. A maximum lymph node standardized uptake value of >2.5 in PET scans was interpreted as positive. A total of 17 patients had positive preoperative PET/CT findings in their hilar lymph nodes, while the remaining 11 had negative findings. With regard to extracapsular nodal invasion, the PET/CT findings (P=0.0005) and the histological findings (squamous cell carcinoma, P=0.05) were found to be significant predictors in the univariate analysis. In the multivariate analysis, the PET/CT findings were the only independent predictor (P=0.0004). The requirement for extensive pulmonary resection (sleeve lobectomy, bilobectomy or pneumonectomy) was significantly more frequent in the patient group with positive compared with the group with negative PET/CT findings (76 vs. 9%, respectively, P=0.01). Therefore, the PET/CT findings in the hilar lymph nodes were useful for the prediction of extracapsular invasion and, consequently, for the estimation of possible extensive pulmonary resection. PMID:26623046

Predicted extracapsular invasion of hilar lymph node metastasis by fusion positron emission tomography/computed tomography in patients with lung cancer.

PubMed

Makino, Takashi; Hata, Yoshinobu; Otsuka, Hajime; Koezuka, Satoshi; Isobe, Kazutoshi; Tochigi, Nobumi; Shiraga, Nobuyuki; Shibuya, Kazutoshi; Homma, Sakae; Iyoda, Akira

2015-09-01

Intraoperative detection of hilar lymph node metastasis, particularly with extracapsular invasion, may affect the surgical procedure in patients with lung cancer, as the preoperative estimation of hilar lymph node metastasis is unsatisfactory. The aim of this study was to investigate whether fusion positron emission tomography/computed tomography (PET/CT) is able to predict extracapsular invasion of hilar lymph node metastasis. Between April, 2007 and April, 2013, 509 patients with primary lung cancer underwent surgical resection at our institution, among whom 28 patients exhibiting hilar lymph node metastasis (at stations 10 and 11) were enrolled in this study. A maximum lymph node standardized uptake value of >2.5 in PET scans was interpreted as positive. A total of 17 patients had positive preoperative PET/CT findings in their hilar lymph nodes, while the remaining 11 had negative findings. With regard to extracapsular nodal invasion, the PET/CT findings (P=0.0005) and the histological findings (squamous cell carcinoma, P=0.05) were found to be significant predictors in the univariate analysis. In the multivariate analysis, the PET/CT findings were the only independent predictor (P=0.0004). The requirement for extensive pulmonary resection (sleeve lobectomy, bilobectomy or pneumonectomy) was significantly more frequent in the patient group with positive compared with the group with negative PET/CT findings (76 vs. 9%, respectively, P=0.01). Therefore, the PET/CT findings in the hilar lymph nodes were useful for the prediction of extracapsular invasion and, consequently, for the estimation of possible extensive pulmonary resection.

Correlation of human papilloma virus status with quantitative perfusion/diffusion/metabolic imaging parameters in the oral cavity and oropharyngeal squamous cell carcinoma: comparison of primary tumour sites and metastatic lymph nodes.

PubMed

Han, M; Lee, S J; Lee, D; Kim, S Y; Choi, J W

2018-05-17

To investigate the differences in perfusion/diffusion/metabolic imaging parameters according to human papilloma virus (HPV) status in the oral cavity and oropharyngeal squamous cell carcinoma (OC-OPSCC), separately in primary tumour sites and metastatic lymph nodes. This retrospective study comprised 41 patients with primary OC-OPSCCs and 29 patients with metastatic lymph nodes. The perfusion/diffusion/metabolic imaging parameters were measured at the primary tumour and the largest ipsilateral metastatic lymph node. The quantitative parameters were compared between the HPV-positive and -negative groups. The HPV-positivity was 39% (16 patients) for the primary tumours and 51.7% (15 patients) for the metastatic lymph nodes. Patients with HPV-positive tumours had a lower T stage (p=0.034). The metastatic lymph nodes for the HPV-positive patients were bulkier (p=0.016) and more frequently had cystic morphology (p=0.005). The perfusion parameters were not different, regardless of HPV status. The diffusion parameter (ADC min , p=0.011) of the metastatic lymph nodes in the HPV-positive groups was lower and metabolic parameter (metabolic tumour volume p=0.035 and total lesion glycolysis p=0.037) were higher than those in HPV-negative groups. The diffusion and metabolic parameters of metastatic lymph nodes from OC-OPSCC were different according to HPV status. The perfusion parameters did not clearly represent HPV status. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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.

Concomitant Mycobacterium avium infection and Hodgkin's disease in a lymph node from an HIV-negative child.

PubMed

de Armas, Yaxsier; Capó, Virginia; González, Ida; Mederos, Lilian; Díaz, Raúl; de Waard, Jacobus H; Rodríguez, Alberto; García, Yarmila; Cabanas, Ricardo

2011-03-01

We report a case of an immunocompetent child with simultaneously an infection with Mycobacterium avium and Hodgkin's disease in a cervical lymph node. A positive PCR result for M. avium on a biopsy of the lymph node directed the definitive diagnosis for both etiologies and avoided a possible dissemination of this infection after chemotherapy was started.

Increased copy number of the DLX4 homeobox gene in breast axillary lymph node metastasis

PubMed Central

Torresan, Clarissa; Oliveira, Márcia M.C.; Pereira, Silma R.F.; Ribeiro, Enilze M.S.F.; Marian, Catalin; Gusev, Yuriy; Lima, Rubens S.; Urban, Cicero A.; Berg, Patricia E.; Haddad, Bassem R.; Cavalli, Iglenir J.; Cavalli, Luciane R.

2017-01-01

DLX4 is a homeobox gene strongly implicated in breast tumor progression and invasion. Our main objective was to determine the DLX4 copy number status in sentinel lymph node (SLN) metastasis to assess its involvement in the initial stages of the axillary metastatic process. A total of 37 paired samples of SLN metastasis and primary breast tumors (PBT) were evaluated by fluorescence in situ hybridization, quantitative polymerase chain reaction and array comparative genomic hybridization assays. DLX4 increased copy number was observed in 21.6% of the PBT and 24.3% of the SLN metastasis; regression analysis demonstrated that the DLX4 alterations observed in the SLN metastasis were dependent on the ones in the PBT, indicating that they occur in the primary tumor cell populations and are maintained in the early axillary metastatic site. In addition, regression analysis demonstrated that DLX4 alterations (and other DLX and HOXB family members) occurred independently of the ones in the HER2/NEU gene, the main amplification driver on the 17q region. Additional studies evaluating DLX4 copy number in non-SLN axillary lymph nodes and/or distant breast cancer metastasis are necessary to determine if these alterations are carried on and maintained during more advanced stages of tumor progression and if could be used as a predictive marker for axillary involvement. PMID:24947980

Beyond the Briganti nomogram: Individualisation of lymphadenectomy using selective sentinel node biopsy during radical prostatectomy for prostate cancer.

PubMed

Monserrat-Monfort, J J; Martinez-Sarmiento, M; Vera-Donoso, C D; Vera-Pinto, V; Sopena-Novales, P; Bello-Arqués, P; Boronat-Tormo, F

To validate the technique of selective sentinel node biopsy for diagnosing and staging intermediate to high-risk prostate cancer by comparing the technique with conventional extended lymphadenectomy (eLFD) in a prospective, longitudinal comparative study. We applied the technique to 45 patients. After an intraprostatic injection of 99m Tc-nanocolloid and preoperative single-photon emission computed tomography (SPECT/CT), we extracted the sentinel lymph nodes, guided by a portable Sentinella® gamma camera and a laparoscopic gamma-ray detection probe. The eLFD was completed to establish the negative predictive value of the technique. SPECT/CT showed radiotracer deposits outside the eLFD territory in 73% of the patients and the laparoscopic gamma probe in 60%. The mean number of active foci per patient was 4.3 in the SPECT/CT and 3.2 in the laparoscopic gamma probe. The mean number of extracted sentinel lymph nodes was 4.3 (0-14), with 26% outside the eLFD territory. The lymph nodes were metastatic in 10 patients (22%), 6/40 (15%) when the prostatectomy was the primary treatment. In all cases with metastatic lymph nodes, there was at least one positive sentinel node. Metastatic sentinel lymph nodes were found outside the eLFD territory in 3/10 patients (30%). The sensitivity was 100%, the specificity was 94.73%, the positive predictive value was 81.81%, and the negative predictive value was 100%. Selective sentinel node biopsy is superior to eLFD for diagnosing lymph node involvement and can avoid eLFD when metastatic sentinel lymph nodes are not found (85%), with the consequent functional advantages. Copyright © 2016 AEU. 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.

Regional lymph node staging using lymphotropic nanoparticle enhanced magnetic resonance imaging with ferumoxtran-10 in patients with penile cancer.

PubMed

Tabatabaei, Shahin; Harisinghani, Mukesh; McDougal, W Scott

2005-09-01

We evaluated lymphotropic nanoparticle enhanced magnetic resonance imaging (LNMRI) with ferumoxtran-10 in determining the presence of regional lymph node metastases in patients with penile cancer. Seven patients with squamous cell carcinoma of the penis underwent LNMRI. All patients subsequently underwent groin dissection and the nodal images were correlated with histology. We found that LNMRI had sensitivity, specificity, and positive and negative predictive values of 100%, 97%, 81.2% and 100%, respectively, in predicting the presence of regional lymph node metastases in patients with penile cancer. Lymph node scanning using LNMRI accurately predicts the pathological status of regional lymph nodes in patients with cancer of the penis. LNMRI may accurately triage patients for regional lymphadenectomy.

Clinical significance of lymph node metastasis in gastric cancer

PubMed Central

Deng, Jing-Yu; Liang, Han

2014-01-01

Gastric cancer, one of the most common malignancies in the world, frequently reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection, which results in poor prognosis. Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer. Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials, it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year follow-up study. Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide, but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis. It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer. Besides, the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer. PMID:24744586

Penile Cancer: Contemporary Lymph Node Management.

PubMed

O'Brien, Jonathan S; Perera, Marlon; Manning, Todd; Bozin, Mike; Cabarkapa, Sonja; Chen, Emily; Lawrentschuk, Nathan

2017-06-01

In penile cancer, the optimal diagnostics and management of metastatic lymph nodes are not clear. Advances in minimally invasive staging, including dynamic sentinel lymph node biopsy, have widened the diagnostic repertoire of the urologist. We aimed to provide an objective update of the recent trends in the management of penile squamous cell carcinoma, and inguinal and pelvic lymph node metastases. We systematically reviewed several medical databases, including the Web of Science® (with MEDLINE®), Embase® and Cochrane databases, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines. The search terms used were penile cancer, lymph node, sentinel node, minimally invasive, surgery and outcomes, alone and in combination. Articles pertaining to the management of lymph nodes in penile cancer were reviewed, including original research, reviews and clinical guidelines published between 1980 and 2016. Accurate and minimally invasive lymph node staging is of the utmost importance in the surgical management of penile squamous cell carcinoma. In patients with clinically node negative disease, a growing body of evidence supports the use of sentinel lymph node biopsies. Dynamic sentinel lymph node biopsy exposes the patient to minimal risk, and results in superior sensitivity and specificity profiles compared to alternate nodal staging techniques. In the presence of locoregional disease, improvements in inguinal or pelvic lymphadenectomy have reduced morbidity and improved oncologic outcomes. A multimodal approach of chemotherapy and surgery has demonstrated a survival benefit for patients with advanced disease. Recent developments in lymph node management have occurred in penile cancer, such as minimally invasive lymph node diagnosis and intervention strategies. These advances have been met with a degree of controversy in the contemporary literature. Current data suggest that dynamic sentinel lymph node biopsy provides excellent sensitivity and specificity for detecting lymph node metastases. More robust long-term data on multicenter patient cohorts are required to determine the optimal management of lymph nodes in penile cancer. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

Cost comparison of axillary sentinel lymph node detection and axillary lymphadenectomy in early breast cancer. A national study based on a prospective multi-institutional series of 985 patients ‘on behalf of the Group of Surgeons from the French Unicancer Federation’

PubMed Central

Classe, J. M.; Baffert, S.; Sigal-Zafrani, B.; Fall, M.; Rousseau, C.; Alran, S.; Rouanet, P.; Belichard, C.; Mignotte, H.; Ferron, G.; Marchal, F.; Giard, S.; Tunon de Lara, C.; Le Bouedec, G.; Cuisenier, J.; Werner, R.; Raoust, I.; Rodier, J.-F.; Laki, F.; Colombo, P.-E.; Lasry, S.; Faure, C.; Charitansky, H.; Olivier, J.-B.; Chauvet, M.-P.; Bussières, E.; Gimbergues, P.; Flipo, B.; Houvenaeghel, G.; Dravet, F.; Livartowski, A.

2012-01-01

Background: Our objective was to assess the global cost of the sentinel lymph node detection [axillary sentinel lymph node detection (ASLND)] compared with standard axillary lymphadenectomy [axillary lymph node dissection (ALND)] for early breast cancer patients. Patients and methods: We conducted a prospective, multi-institutional, observational, cost comparative analysis. Cost calculations were realized with the micro-costing method from the diagnosis until 1 month after the last surgery. Results: Eight hundred and thirty nine patients were included in the ASLND group and 146 in the ALND group. The cost generated for a patient with an ASLND, with one preoperative scintigraphy, a combined method for sentinel node detection, an intraoperative pathological analysis without lymphadenectomy, was lower than the cost generated for a patient with lymphadenectomy [€2947 (σ = 580) versus €3331 (σ = 902); P = 0.0001]. Conclusion: ASLND, involving expensive techniques, was finally less expensive than ALND. The length of hospital stay was the cost driver of these procedures. The current observational study points the heterogeneous practices for this validated and largely diffused technique. Several technical choices have an impact on the cost of ASLND, as intraoperative analysis allowing to reduce rehospitalization rate for secondary lymphadenectomy or preoperative scintigraphy, suggesting possible savings on hospital resources. PMID:21896543

[Presence of intramammary lymph nodes in the preoperative lymphoscintigraphy to locate the sentinel lymph node. Clinical significance].

PubMed

Nogareda, Z; Álvarez, A; Perlaza, P; Caparrós, F X; Alonso, I; Paredes, P; Vidal-Sicart, S

2015-01-01

The routes of lymphatic drainage from a breast cancer are the axilla (the most frequent) and the extra axillary regions. Among the latter, there are the so-called intrammamary lymph nodes (IMLN). This study has aimed to assess the incidence of IMLNs in our patients and study the evolution of these cases with IMLN in the lymphoscintigraphy. Thirty-eight patients (out of 1725) with IMLN in the pre-operative lymphoscintigraphy were assessed. During the surgical procedure, using a gamma probe, IMLNs were located and excised. After their harvesting, a meticulous surgical field scan was performed. When the axillary sentinel node was positive for metastasis, a complete axillary lymphadenectomy was performed. In those where the axillary sentinel node was negative and IMLN was positive (IMLN+), axillary lymphadenectomy was also performed, except for one case. Thirty-four out of the 38 IMLNs were obtained (89.5%), because no lymphatic tissue was found in pathology analysis in three cases (8%) and in one patient (3%) IMLN was not found during surgery. Ten (26%) metastatic IMLNs were located and the remaining 24 IMLNs cases (63%) were metastasis-free. During the clinical follow-up, one patient with IMLN+ developed hepatic metastases. The remaining 33 patients did not present any recurrence. No follow-up data were available for three patients. IMLN and axillary sentinel node biopsy are recommended when both are depicted in preoperative lymphoscintigraphy. The axilla treatment will only depend on the axillary sentinel node status. Based on the data from other authors and our own experience, avoiding the axillary lymphadenectomy when a metastatic IMLN without axillary involvement seems reasonable. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

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.

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

Detection of lymph node metastases with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging in oesophageal cancer: a feasibility study

PubMed Central

van der Jagt, E.J.; van Westreenen, H.L.; van Dullemen, H.M.; Kappert, P.; Groen, H.; Sietsma, J.; Oudkerk, M.; Plukker, J.Th.M.; van Dam, G.M.

2009-01-01

Abstract Aim: In this feasibility study we investigated whether magnetic resonance imaging (MRI) with ultrasmall superparamagnetic iron oxide (USPIO) can be used to identify regional and distant lymph nodes, including mediastinal and celiac lymph node metastases in patients with oesophageal cancer. Patients and methods: Ten patients with a potentially curative resectable cancer of the oesophagus were eligible for this study. All patients included in the study had positive lymph nodes on conventional staging (including endoscopic ultrasound, computed tomography and fluorodeoxyglucose-positron emission tomography). Nine patients underwent MRI + USPIO before surgery. Results were restricted to those patients who had both MRI + USPIO and histological examination. Results were compared with conventional staging and histopathologic findings. Results: One patient was excluded due to expired study time. Five out of 9 patients underwent an exploration; in 1 patient prior to surgery MRI + USPIO diagnosed liver metastases and in 3 patients an oesophageal resection was performed. USPIO uptake in mediastinal lymph nodes was seen in 6 out of 9 patients; in 3 patients non-malignant nodes were not visible. In total, 9 lymph node stations (of 6 patients) were separately analysed; 7 lymph node stations were assessed as positive (N1) on MRI+USPIO compared with 9 by conventional staging. According to histology findings, there was one false-positive and one false-negative result in MRI + USPIO. Also, conventional staging modalities had one false-positive and one false-negative result. MRI + USPIO had surplus value in one patient. Not all lymph node stations could be compared due to unforeseen explorations. No adverse effects occurred after USPIO infusion. Conclusion: MRI+USPIO identified the majority of mediastinal and celiac (suspect) lymph nodes in 9 patients with oesophageal cancer. MRI+USPIO could have an additional value in loco-regional staging; however, more supplementary research is needed. PMID:19414293

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.

Impact of affected lymph nodes on long-term outcome after surgical therapy of alveolar echinococcosis.

PubMed

Hillenbrand, Andreas; Beck, Annika; Kratzer, Wolfgang; Graeter, Tilmann; Barth, Thomas F E; Schmidberger, Julian; Möller, Peter; Henne-Bruns, Doris; Gruener, Beate

2018-06-16

Alveolar echinococcosis (AE) is a life-threatening helminthic disease. In humans, AE mostly affects the liver; the regional hepatic lymph nodes may be involved, indicating dissemination of AE from the liver. To achieve complete removal of the disease, enlarged hepatic lymph nodes may be resected during surgical treatment. We evaluated the frequency of affected lymph nodes by conventional microscopic and immunohistochemical analyses including detection of small particles of Echinococcus multilocularis (spem). Furthermore, we analyzed the association of resection of enlarged and affected lymph nodes with long-term outcome after surgical therapy of patients who underwent surgery with curative intent. We identified 43 patients who underwent hepatic surgery with curative intent with lymph node resection for AE. We analyzed the cohort for the manifestation of the parasite in the resected lymph nodes by conventional histology and by immunohistochemistry and compared these data with the further course of AE. Microscopically infected lymph nodes (laminar layer visible) were found in 7 out of these 43 patients (16%). In more than three quarters (25/32) of all specimens investigated, lymph nodes showed spems when stained with antibody against Em2G11, a monoclonal antibody specific for the Em2 antigen of the Echinococcus multilocularis metacestode. Most frequently, lymph nodes were resected due to enlargement. The median size of microscopically affected lymph nodes was 2 cm (range, 1.2 to 2.5 cm), the median size of immunohistochemically and non-affected lymph nodes was 1.3 cm each (range, "small" to 2.3 or 2.5 cm, respectively). Median follow-up was 8 years for all patients, 5 years for patients with lymph node resection, and 4 years for patients with infested lymph nodes. Overall, recurrent disease was seen in ten patients (10/109; 9%) after a median period of 1.5 years (range, 4 months to 4 years). None of the seven patients with conventionally microscopically affected lymph nodes suffered from recurrent disease. One patient with negative resected nodes and one patient with spems showed recurrent disease after 4 and 35 months, respectively. Lymph node involvement in AE is frequent, particularly when evaluated by immunohistochemical examination of lymph nodes with the monoclonal antibody Em2G11. Affected lymph nodes tend to be larger in size. Lymph node involvement is not associated with recurrent disease and therefore warrants further analysis of the biological significance of lymph node involvement.

Dual time point 2-deoxy-2-[18F]fluoro-D-glucose PET/CT: nodal staging in locally advanced breast cancer.

PubMed

García Vicente, A M; Soriano Castrejón, A; Cruz Mora, M Á; Ortega Ruiperez, C; Espinosa Aunión, R; León Martín, A; González Ageitos, A; Van Gómez López, O

2014-01-01

To assess dual time point 2-deoxy-2-[(18)F]fluoro-D-glucose (18)(F)FDG PET-CT accuracy in nodal staging and in detection of extra-axillary involvement. Dual time point [(18)F] FDG PET/CT scan was performed in 75 patients. Visual and semiquantitative assessment of lymph nodes was performed. Semiquantitative measurement of SUV and ROC-analysis were carried out to calculate SUV(max) cut-off value with the best diagnostic performance. Axillary and extra-axillary lymph node chains were evaluated. Sensitivity and specificity of visual assessment was 87.3% and 75%, respectively. SUV(max) values with the best sensitivity were 0.90 and 0.95 for early and delayed PET, respectively. SUV(max) values with the best specificity were 1.95 and 2.75, respectively. Extra-axillary lymph node involvement was detected in 26.7%. FDG PET/CT detected extra-axillary lymph node involvement in one-fourth of the patients. Semiquantitative lymph node analysis did not show any advantage over the visual evaluation. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Transcriptional profile of fibroblasts obtained from the primary site, lymph node and bone marrow of breast cancer patients.

PubMed

Del Valle, Paulo Roberto; Milani, Cintia; Brentani, Maria Mitzi; Katayama, Maria Lucia Hirata; de Lyra, Eduardo Carneiro; Carraro, Dirce Maria; Brentani, Helena; Puga, Renato; Lima, Leandro A; Rozenchan, Patricia Bortman; Nunes, Bárbara Dos Santos; Góes, João Carlos Guedes Sampaio; Azevedo Koike Folgueira, Maria Aparecida

2014-09-01

Cancer-associated fibroblasts (CAF) influence tumor development at primary as well as in metastatic sites, but there have been no direct comparisons of the transcriptional profiles of stromal cells from different tumor sites. In this study, we used customized cDNA microarrays to compare the gene expression profile of stromal cells from primary tumor (CAF, n = 4), lymph node metastasis (N+, n = 3) and bone marrow (BM, n = 4) obtained from breast cancer patients. Biological validation was done in another 16 samples by RT-qPCR. Differences between CAF vs N+, CAF vs BM and N+ vs BM were represented by 20, 235 and 245 genes, respectively (SAM test, FDR < 0.01). Functional analysis revealed that genes related to development and morphogenesis were overrepresented. In a biological validation set, NOTCH2 was confirmed to be more expressed in N+ (vs CAF) and ADCY2, HECTD1, HNMT, LOX, MACF1, SLC1A3 and USP16 more expressed in BM (vs CAF). Only small differences were observed in the transcriptional profiles of fibroblasts from the primary tumor and lymph node of breast cancer patients, whereas greater differences were observed between bone marrow stromal cells and the other two sites. These differences may reflect the activities of distinct differentiation programs.

Transcriptional profile of fibroblasts obtained from the primary site, lymph node and bone marrow of breast cancer patients

PubMed Central

Del Valle, Paulo Roberto; Milani, Cintia; Brentani, Maria Mitzi; Katayama, Maria Lucia Hirata; de Lyra, Eduardo Carneiro; Carraro, Dirce Maria; Brentani, Helena; Puga, Renato; Lima, Leandro A.; Rozenchan, Patricia Bortman; Nunes, Bárbara dos Santos; Góes, João Carlos Guedes Sampaio; Azevedo Koike Folgueira, Maria Aparecida

2014-01-01

Cancer-associated fibroblasts (CAF) influence tumor development at primary as well as in metastatic sites, but there have been no direct comparisons of the transcriptional profiles of stromal cells from different tumor sites. In this study, we used customized cDNA microarrays to compare the gene expression profile of stromal cells from primary tumor (CAF, n = 4), lymph node metastasis (N+, n = 3) and bone marrow (BM, n = 4) obtained from breast cancer patients. Biological validation was done in another 16 samples by RT-qPCR. Differences between CAF vs N+, CAF vs BM and N+ vs BM were represented by 20, 235 and 245 genes, respectively (SAM test, FDR < 0.01). Functional analysis revealed that genes related to development and morphogenesis were overrepresented. In a biological validation set, NOTCH2 was confirmed to be more expressed in N+ (vs CAF) and ADCY2, HECTD1, HNMT, LOX, MACF1, SLC1A3 and USP16 more expressed in BM (vs CAF). Only small differences were observed in the transcriptional profiles of fibroblasts from the primary tumor and lymph node of breast cancer patients, whereas greater differences were observed between bone marrow stromal cells and the other two sites. These differences may reflect the activities of distinct differentiation programs. PMID:25249769

LYMPHOCYTIC THYROIDITIS IS ASSOCIATED WITH INCREASED NUMBER OF BENIGN CERVICAL NODES AND FEWER CENTRAL NECK COMPARTMENT METASTATIC LYMPH NODES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

PubMed

Donangelo, Ines; Walts, Ann E; Bresee, Catherine; Braunstein, Glenn D

2016-10-01

Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection. From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013. Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT. Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear. CCND = central compartment node dissection DTC = differentiated thyroid cancer HT = Hashimoto thyroiditis LT = lymphocytic thyroiditis TgAb = thyroglobulin antibody TPO = thyroid peroxidase.

Adenoid Cystic Carcinoma of the Breast: A Clinical Case Report.

PubMed

Kocaay, Akin Firat; Celik, Suleyman Utku; Hesimov, Ilkin; Eker, Tevfik; Percinel, Sibel; Demirer, Seher

2016-10-01

Adenoid cystic carcinoma (ACC) is an uncommon tumor of the breast, accounting for approximately 0.1% to 1% of all breast cancers. It is characterized by rare lymph node involvement and distant metastasis, and associated with a favorable prognosis with excellent survival, despite its triple-negative status. In the current state of knowledge, results of breast-conserving treatment with postoperative radiotherapy seem to be equivalent to mastectomy alone, with respect to survival for ACC of the breast. Due to its rarity, there is no consensus on optimal treatment for patients with ACC. Otherwise, the role of chemotherapy and hormonal therapy remains controversial. Further clinical studies are required to compare treatment options for ACC. But, a long-term follow-up is very important and mandatory for affected patients, due to the late onset of local relapse and occurrence of distant metastasis. Here, we report the case of a patient who presented with a palpable breast mass in the left breast that turned out to be an ACC of the breast.

Immunoreactivities of human nonmetastatic clone 23 and p53 products are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients.

PubMed

Tee, Y T; Wang, P H; Ko, J L; Chen, G D; Chang, H; Lin, L Y

2007-01-01

To assess the relation between expressions of human nonmetastatic clone 23 (nm23-H1) and p53 in cervical cancer, their relationships with lymph node metastasis, and further to examine their predictive of lymph node metastases. nm23-H1 and p53 expression profiles were visualized by immunohistochemistry in early-stage cervical cancer specimens. Immunoreactivities of nm23-H1 and p53 were disassociated. The independent variables related with lymph node metastases were grade of cancer cell differentiation (p < 0.029) and stromal invasion (p < 0.039). Sensitivity, specificity, positive and negative predictive values, and accuracy for lymph node metastasis were calculated to be 91.7%, 13.5%, 25.6%, 83.3%, and 32.7% for nm23-H1 and 66.7%, 51.4%, 30.8%, 82.6%, and 55.1% for p53. Nm23-H1 and p53 are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients. However, stromal invasion and cell differentiation can predict lymph node metastasis.

Fluorescence spectroscopy using indocyanine green for lymph node mapping

NASA Astrophysics Data System (ADS)

Haj-Hosseini, Neda; Behm, Pascal; Shabo, Ivan; Wârdell, Karin

2014-02-01

The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue.

Comparison of systematic mediastinal lymph node dissection versus systematic sampling for lung cancer staging and completeness of surgery.

PubMed

Wu, Nan; Yan, Shi; Lv, Chao; Feng, Yuan; Wang, Yuzhao; Zhang, Lijian; Yang, Yue

2011-12-01

This self-controlled prospective study was designed to investigate the efficacy of systematic sampling (SS), compared with systematic mediastinal lymph node dissection (SMLD), for pathologic staging and completeness of surgery. Over a period of 11 mo, 110 patients with lung cancer were enlisted and treated by pulmonary resection. Surgeons systematically sampled mediastinal lymph nodes prior to pulmonary resection, and after pulmonary resection SMLD was performed to each patient using Mountain's procedure [1]. After SMLD, pN status was classified as N0 in 57 cases, N1 in 27, and N2 in 26. SS detected 38.3% of pooled nodes and 37.6% of pooled positive nodes collected from SMLD. Pathologic diagnosis after SS was understaged in nine cases (8.2%) compared with staging after SMLD. However, surgery was incomplete in 24 cases (21.8%) if SMLD was not performed after sampling. Negative predictive value for SS was 86.8% on the right side, and 95.0% on the left. Three categories were generated according to pN status: negative nodes in SS and additional negative nodes from SMLD [S(-)D(-)], negative nodes in SS but additional positive nodes from SMLD [S(-)D(+)], and positive nodes in SS [S(+)D(+)]. cN2 (P=0.000) and CEA level (P=0.001) were correlated with pN status. There was significant overall survival difference between non-N2 group and N2 group (P=0.002). SMLD may harvest about three times of mediastinal lymph nodes compared with SS. SS is more likely to affect the completeness of surgery instead of underrating pathologic stage. Copyright © 2011 Elsevier Inc. All rights reserved.

The use of {sup 99m}Tc-Al{sub 2}O{sub 3} for detection of sentinel lymph nodes in breast cancer

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

Sinilkin, I., E-mail: sinilkinig@oncology.tomsk.ru; Chernov, V.; Medvedeva, A.

2016-08-02

Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n = 34) were injected with radioactive {sup 99m}Tc-Al{sub 2}O{sub 3}, and Group II patients (n = 30) received {sup 99m}Tc-labeled phytate colloid. A total of 37 SLNs were detected in Group I patients. The number ofmore » identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. 18 hours after {sup 99m}Tc-Al{sub 2}O{sub 3} injection, the percentage of its accumulation in the SLN was 7–11% (of the counts in the injection site) by SPECT and 17–31% by gamma probe detection. In Group II SLNs were detected in 27 patients. 18 hours after injection of the phytate colloid the percentage of its accumulation in the SLN was 1.5–2% out of the counts in the injection site by SPECT and 4–7% by gamma probe. The new radiopharmaceutical based on the {sup 99m}Tc-Al{sub 2}O{sub 3} demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. The sensitivity and specificity of {sup 99m}Tc-Al{sub 2}O{sub 3} were 100% for both SPECT and intraoperative gamma probe identification.« less

United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) randomized controlled trial comparing targeted nodal assessment and ultrastaging with standard pathological evaluation for colon cancer.

PubMed

Nissan, Aviram; Protic, Mladjan; Bilchik, Anton J; Howard, Robin S; Peoples, George E; Stojadinovic, Alexander

2012-09-01

Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC. In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer. Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC. TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.

Sentinel lymph nodes detection with an imaging system using Patent Blue V dye as fluorescent tracer

NASA Astrophysics Data System (ADS)

Tellier, F.; Steibel, J.; Chabrier, R.; Rodier, J. F.; Pourroy, G.; Poulet, P.

2013-03-01

Sentinel lymph node biopsy is the gold standard to detect metastatic invasion from primary breast cancer. This method can help patients avoid full axillary chain dissection, thereby decreasing the risk of morbidity. We propose an alternative to the traditional isotopic method, to detect and map the sentinel lymph nodes. Indeed, Patent Blue V is the most widely used dye in clinical routine for the visual detection of sentinel lymph nodes. A Recent study has shown the possibility of increasing the fluorescence quantum yield of Patent Blue V, when it is bound to human serum albumin. In this study we present a preclinical fluorescence imaging system to detect sentinel lymph nodes labeled with this fluorescent tracer. The setup is composed of a black and white CCD camera and two laser sources. One excitation source with a laser emitting at 635 nm and a second laser at 785 nm to illuminate the region of interest. The prototype is operated via a laptop. Preliminary experiments permitted to determine the device sensitivity in the μmol.L-1 range as regards the detection of PBV fluorescence signals. We also present a preclinical evaluation performed on Lewis rats, during which the fluorescence imaging setup detected the accumulation and fixation of the fluorescent dye on different nodes through the skin.

Comparison of Positron Emission Tomography Scanning and Sentinel Node Biopsy in the Detection of Inguinal Node Metastases in Patients With Anal Cancer

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

Mistrangelo, Massimiliano, E-mail: mistrangelo@katamail.co; Centre of Minimally Invasive Surgery, University of Turin; Pelosi, Ettore

2010-05-01

Background: Inguinal lymph node metastases in patients with anal cancer are an independent prognostic factor for local failure and overall mortality. Inguinal lymph node status can be adequately assessed with sentinel node biopsy, and the radiotherapy strategy can subsequently be changed. We compared this technique vs. dedicated 18F-fluorodeoxyglucose positron emission tomography (PET) to determine which was the better tool for staging inguinal lymph nodes. Methods and Materials: In our department, 27 patients (9 men and 18 women) underwent both inguinal sentinel node biopsy and PET-CT. PET-CT was performed before treatment and then at 1 and 3 months after treatment. Results:more » PET-CT scans detected no inguinal metastases in 20 of 27 patients and metastases in the remaining 7. Histologic analysis of the sentinel lymph node detected metastases in only three patients (four PET-CT false positives). HIV status was not found to influence the results. None of the patients negative at sentinel node biopsy developed metastases during the follow-up period. PET-CT had a sensitivity of 100%, with a negative predictive value of 100%. Owing to the high number of false positives, PET-CT specificity was 83%, and positive predictive value was 43%. Conclusions: In this series of patients with anal cancer, inguinal sentinel node biopsy was superior to PET-CT for staging inguinal lymph nodes.« less

Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous melanoma.

PubMed

Korn, Jason M; Tellez-Diaz, Alejandra; Bartz-Kurycki, Marisa; Gastman, Brian

2014-04-01

Sentinel lymph node biopsy is the standard of care for intermediate-depth and high-risk thin melanomas. Recently, indocyanine green and near-infrared imaging have been used to aid in sentinel node biopsy. The present study aimed to determine the feasibility of sentinel lymph node biopsy with indocyanine green SPY Elite navigation and to critically evaluate the technique compared with the standard modalities. A retrospective review of 90 consecutive cutaneous melanoma patients who underwent sentinel lymph node biopsy was performed. Two cohorts were formed: group A, which had sentinel lymph node biopsy performed with blue dye and radioisotope; and group B, which had sentinel lymph node biopsy performed with radioisotope and indocyanine green SPY Elite navigation. The cohorts were compared to assess for differences in localization rates, sensitivity and specificity of sentinel node identification, and length of surgery. The sentinel lymph node localization rate was 79.4 percent using the blue dye method, 98.0 percent using the indocyanine green fluorescence method, and 97.8 percent using the radioisotope/handheld gamma probe method. Indocyanine green fluorescence detected more sentinel lymph nodes than the vital dye method alone (p = 0.020). A trend toward a reduction in length of surgery was noted in the SPY Elite cohort. Sentinel lymph node mapping and localization in cutaneous melanoma with the indocyanine green SPY Elite navigation system is technically feasible and may offer several advantages over current modalities, including higher sensitivity and specificity, decreased number of lymph nodes sampled, decreased operative time, and potentially lower false-negative rates. Diagnostic, II.

Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies

PubMed Central

Wang, Li; Guyatt, Gordon H.; Kennedy, Sean A.; Romerosa, Beatriz; Kwon, Henry Y.; Kaushal, Alka; Chang, Yaping; Craigie, Samantha; de Almeida, Carlos P.B.; Couban, Rachel J.; Parascandalo, Shawn R.; Izhar, Zain; Reid, Susan; Khan, James S.; McGillion, Michael; Busse, Jason W.

2016-01-01

Background: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. Methods: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case–control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. Results: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24–1.48), radiotherapy (OR 1.35, 95% CI 1.16–1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73–3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03–1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01–1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. Interpretation: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery. PMID:27402075

Involvement of chemokine receptors in breast cancer metastasis

NASA Astrophysics Data System (ADS)

Müller, Anja; Homey, Bernhard; Soto, Hortensia; Ge, Nianfeng; Catron, Daniel; Buchanan, Matthew E.; McClanahan, Terri; Murphy, Erin; Yuan, Wei; Wagner, Stephan N.; Barrera, Jose Luis; Mohar, Alejandro; Verástegui, Emma; Zlotnik, Albert

2001-03-01

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

Sonographic findings predictive of central lymph node metastasis in patients with papillary thyroid carcinoma: influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography.

PubMed

Yoo, Yeon Hwa; Kim, Jeong-Ah; Son, Eun Ju; Youk, Ji Hyun; Kwak, Jin Young; Kim, Eun-Kyung; Park, Cheong Soo

2013-12-01

To analyze sonographic findings suggesting central lymph node metastasis of papillary thyroid carcinoma and to evaluate the influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography for predicting central lymph node metastasis. A total of 124 patients (101 female and 23 male; mean age, 47.5 years; range, 21-74 years) underwent sonographically guided fine-needle aspiration in central lymph nodes from January 2008 to July 2011. Sonographic features of size, shape, margin, thickening of the cortex, cortical echogenicity, presence of a hilum, cystic changes, calcification, and vascularity of enlarged lymph nodes were analyzed before fine-needle aspiration and classified into 2 categories (probably benign and suspicious). Sonographic findings were correlated with the pathologic diagnosis and associated chronic lymphocytic thyroiditis. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of sonography for predicting central lymph node metastasis according to the associated thyroiditis. Fifty-one lymph nodes (39.5%) were malignant, and 73 (60.5%) were benign. On univariate analysis, size, shape, margin, cortical thickening, cortical echogenicity, cystic changes, calcification, and vascularity were significantly different between the benign and metastatic nodes (P < .05). On multivariate analysis, eccentric cortical thickening (odds ratio, 26.59; 95% confidence interval [CI], 3.26-216.66) and hyper echogenicity of the cortex (odds ratio, 18.46; 95% CI, 2.44-139.64) were significantly associated with malignant nodes (P < .05). The area under the curve values for sonography for predicting metastasis were 0.756 (95% CI, 0.618-0.894) in chronic lymphocytic thyroiditis-positive patients and 0.971 (95% CI, 0.938-1.000) in negative patients. Eccentric cortical thickening and cortical hyperechogenicity were the sonographic findings predictive of central lymph node metastasis from papillary thyroid carcinoma. The diagnostic performance of sonography for predicting metastasis was superior in chronic lymphocytic thyroiditis-negative patients than in positive patients.

Fine needle aspiration of toxoplasmic lymphadenitis in an intramammary lymph node. A case report.

PubMed

Shimizu, K; Ito, I; Sasaki, H; Takada, E; Sunagawa, M; Masawa, N

2001-01-01

Cytologic findings of toxoplasmic lymphadenitis (TL) have been only sporadically reported. Intramammary lymph node is an extremely rare site for TL. A 47-year-old, healthy, female presented with a breast tumor, which was aspirated. The cytomorphologic features were interpreted as suggestive of TL. Histopathology of the excisional biopsy specimen and subsequent serologic examination confirmed the diagnosis. We obtained several characteristic findings in aspiration of TL. Of these, epithelioid cell clusters and monocytoid cells were the most diagnostic.

Lower and reduced expression of EphA4 is associated with advanced TNM stage, lymph node metastasis, and poor survival in breast carcinoma.

PubMed

Sun, Yuejun; Qian, Jianzhong; Lu, Min; Xu, Hongming

2016-09-01

The expression of EphA4 has been well documented in the development of nerve and in certain types of human cancer. Few studies of EphA4, however, have focused on breast carcinoma. In this study, a set of breast carcinomas was subjected to immunohistochemical staining. In normal luminal cells, EphA4 was weakly detected in 11 (14.3 %), moderately detected in 15 (19.5 %) and highly detected in 51 out of 77 (66.2 %) samples, while in breast carcinoma cells, EphA4 was weakly detected in 42 (54.5 %), moderately detected in 19 (24.7 %) and highly detected in 16 out of 77 (20.8 %) samples (P < 0.001). The expression of EphA4 protein was significantly reduced in 68.8 % of breast carcinoma samples comparing with normal cells. The expression of EphA4 was significantly associated with tumor grade (P = 0.003), TNM stage (P = 0.034), lymph node metastasis (P = 0.034) and Ki-67 (P < 0.001). No significant relationship was found between the expression of EphA4 and age, molecular subtypes, and HER2 status. Survival analysis showed that significant association of low expression of EphA4 in tumor cells with short overall survival (P = 0.048) and disease-free survival (P = 0.051). Our data show that EphA4 was reduced in breast carcinoma, which is associated with high grade, advanced TNM stage, lymph node metastasis, and poor outcome of patients. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

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.

Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes

PubMed Central

2012-01-01

Introduction Signal transducer and activator of transcripton-5a (Stat5a) and its close homologue, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome. Methods Stat5a and Stat5b protein levels were quantified in situ in breast-cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data by using multivariate models. Results Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared with normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a- and Stat5b-modulated genes was found. In two cohorts of therapy-naïve, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with a more than fourfold risk of unfavorable outcome. Conclusions Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials. PMID:23036105

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

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.

Axillary silicone lymphadenopathy secondary to augmentation mammaplasty

PubMed Central

Dragoumis, Dimitrios M.; Assimaki, Anthoula S.; Vrizas, Triantafyllos I.; Tsiftsoglou, Aris P.

2010-01-01

We report a case involving a 45-year-old woman, who presented with an axillary mass 10 years after bilateral cosmetic augmentation mammaplasty. A lump was detected in the left axilla, and subsequent mammography and magnetic resonance imaging demonstrated intracapsular rupture of the left breast prosthesis. An excisional biopsy of the left axillary lesion and replacement of the ruptured implant was performed. Histological analysis showed that the axillary lump was lymph nodes containing large amounts of silicone. Silicone lymphadenopathy is an obscure complication of procedures involving the use of silicone. It is thought to occur following the transit of silicone droplets from breast implants to lymph nodes by macrophages and should always be considered as a differential diagnosis in patients in whom silicone prostheses are present. PMID:21217983

Prognostic Significance of the Location of Lymph Node Metastases in Patients With Adenocarcinoma of the Distal Esophagus or Gastroesophageal Junction.

PubMed

Anderegg, Maarten C J; Lagarde, Sjoerd M; Jagadesham, Vamshi P; Gisbertz, Suzanne S; Immanuel, Arul; Meijer, Sybren L; Hulshof, Maarten C C M; Bergman, Jacques J G H M; van Laarhoven, Hanneke W M; Griffin, S Michael; van Berge Henegouwen, Mark I

2016-11-01

To identify the prognostic significance of the location of lymph node metastases in patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma treated with neoadjuvant therapy followed by esophagectomy. Detection of lymph node metastases in the upper mediastinum and around the celiac trunk after neoadjuvant therapy and resection does not alter the TNM classification of esophageal carcinoma. The impact of these distant lymph node metastases on survival remains unclear. Between March 2003 and September 2013, 479 consecutive patients with adenocarcinoma of the distal esophagus or GEJ who underwent transthoracic esophagectomy with en bloc 2-field lymphadenectomy after neoadjuvant therapy were included, and survival was analyzed according to the location of positive lymph nodes in the resection specimen. Two hundred fifty-three patients had nodal metastases in the resection specimen. Of these patients, 92 patients had metastases in locoregional nodes, 114 patients in truncal nodes, 21 patients in the proximal field of the chest, and 26 patients had both positive truncal and proximal field nodes. Median disease-free survival was 170 months in the absence of nodal metastases, 35 months for metastases limited to locoregional nodes, 16 months for positive truncal nodes, 15 months for positive nodes in the proximal field, and 8 months for nodal metastases in both truncal and the proximal field. On multivariate analysis, location of lymph node metastases was independently associated with survival. Location of lymph node metastases is an independent predictor for survival. Relatively distant lymph node metastases along the celiac axis and/or the proximal field have a negative impact on survival. Location of lymph node metastases should therefore be considered in future staging systems of esophageal and GEJ adenocarcinoma.

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

PubMed

Mahmood, Muhammad N; Lee, Min W; Linden, Michael D; Nathanson, S D; Hornyak, Thomas J; Zarbo, Richard J

2002-12-01

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.

Scanning elastic scattering spectroscopy detects metastatic breast cancer in sentinel lymph nodes

NASA Astrophysics Data System (ADS)

Austwick, Martin R.; Clark, Benjamin; Mosse, Charles A.; Johnson, Kristie; Chicken, D. Wayne; Somasundaram, Santosh K.; Calabro, Katherine W.; Zhu, Ying; Falzon, Mary; Kocjan, Gabrijela; Fearn, Tom; Bown, Stephen G.; Bigio, Irving J.; Keshtgar, Mohammed R. S.

2010-07-01

A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20×20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.

[Comparison of two quantitative methods of endobronchial ultrasound real-time elastography for evaluating intrathoracic lymph nodes].

PubMed

Mao, X W; Yang, J Y; Zheng, X X; Wang, L; Zhu, L; Li, Y; Xiong, H K; Sun, J Y

2017-06-12

Objective: To compare the clinical value of two quantitative methods in analyzing endobronchial ultrasound real-time elastography (EBUS-RTE) images for evaluating intrathoracic lymph nodes. Methods: From January 2014 to April 2014, EBUS-RTE examination was performed in patients who received EBUS-TBNA examination in Shanghai Chest Hospital. Each intrathoracic lymph node had a selected EBUS-RTE image. Stiff area ratio and mean hue value of region of interest (ROI) in each image were calculated respectively. The final diagnosis of lymph node was based on the pathologic/microbiologic results of EBUS-TBNA, pathologic/microbiologic results of other examinations and clinical following-up. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were evaluated for distinguishing malignant and benign lesions. Results: Fifty-six patients and 68 lymph nodes were enrolled in this study, of which 35 lymph nodes were malignant and 33 lymph nodes were benign. The stiff area ratio and mean hue value of benign and malignant lesions were 0.32±0.29, 0.62±0.20 and 109.99±28.13, 141.62±17.52, respectively, and statistical differences were found in both of those two methods ( t =-5.14, P <0.01; t =-5.53, P <0.01). The area under curves was 0.813, 0.814 in stiff area ratio and mean hue value, respectively. The optimal diagnostic cut-off value of stiff area ratio was 0.48, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 82.86%, 81.82%, 82.86%, 81.82% and 82.35%, respectively. The optimal diagnostic cut-off value of mean hue value was 126.28, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 85.71%, 75.76%, 78.95%, 83.33% and 80.88%, respectively. Conclusion: Both the stiff area ratio and mean hue value methods can be used for analyzing EBUS-RTE images quantitatively, having the value of differentiating benign and malignant intrathoracic lymph nodes, and the stiff area ratio is better than the mean hue value between the two methods.

[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.

Comparison of MUC4 expression in primary pancreatic cancer and paired lymph node metastases.

PubMed

Ansari, Daniel; Urey, Carlos; Gundewar, Chinmay; Bauden, Monika Posaric; Andersson, Roland

2013-10-01

OBJECTIVE. Mucin 4 (MUC4) is a transmembrane glycoprotein that is expressed in pancreatic ductal adenocarcinoma (PDAC), but not in normal pancreatic tissue. MUC4 has a proposed role in pancreatic tumor progression and metastasis. The purpose of this pilot study was to investigate MUC4 expression during PDAC metastasis by comparing the expression in the primary tumor and paired lymph node metastases from the same patient. MATERIAL AND METHODS. Surgical specimens from 17 cases of primary PDAC and paired lymph node metastases were immunohistochemically analyzed for MUC4 expression. The modified histochemical score (H-score) was used for staining assessment. RESULTS. Positive staining for MUC4 was detected in most primary and metastatic PDAC tumors (15/17 vs. 14/17). The concordance for MUC4 expression in primary tumors and corresponding lymph node metastases was 82%. In two cases, the primary tumor was MUC4-positive and the lymph node metastases were negative, while in one patient with a MUC4-negative primary tumor, the lymph node metastasis was positive. The distribution of H-score for expression of MUC4 significantly correlated (r = 0.615; p = 0.009) between primary tumors and paired metastatic lesions. MUC4 was observed in both primary and matched metastatic tumors with a high level of concordance, suggesting that MUC4 expression is retained following PDAC metastasis.

External ultrasonography of the neck does not add diagnostic value to integrated positron emission tomography-computed tomography (PET-CT) scanning in the diagnosis of cervical lymph node metastases in patients with esophageal carcinoma.

PubMed

Blom, R L G M; Vliegen, R F A; Schreurs, W M J; Belgers, H J; Stohr, I; Oostenbrug, L E; Sosef, M N

2012-08-01

One of the objectives of preoperative imaging in esophageal cancer patients is the detection of cervical lymph node metastases. Traditionally, external ultrasonography of the neck has been combined with computed tomography (CT) in order to improve the detection of cervical metastases. In general, integrated positron emission tomography-computed tomography (PET-CT) has been shown to be superior to CT or PET regarding staging and therefore may limit the role of external ultrasonography of the neck. The objective of this study was to determine the additional value of external ultrasonography of the neck to PET-CT. This study included all patients referred our center for treatment of esophageal carcinoma. Diagnostic staging was performed to determine treatment plan. Cervical lymph nodes were evaluated by external ultrasonography of the neck and PET-CT. In case of suspect lymph nodes on external ultrasonography or PET-CT, fine needle aspiration (FNA) was performed. Between 2008 and 2010, 170 out of 195 referred patients underwent both external ultrasonography of the neck and PET-CT. Of all patients, 84% were diagnosed with a tumor at or below the distal esophagus. In 140 of 170 patients, the cervical region was not suspect; no FNA was performed. Seven out of 170 patients had suspect nodes on both PET-CT and external ultrasonography. Five out of seven patients had cytologically confirmed malignant lymph nodes, one of seven had benign nodes, in one patient FNA was not performed; exclusion from esophagectomy was based on intra-abdominal metastases. In one out of 170 patients, PET-CT showed suspect nodes combined with a negative external ultrasonography; cytology of these nodes was benign. Twenty-two out of 170 patients had a negative PET-CT with suspect nodes on external ultrasonography. In 18 of 22 patients, cervical lymph nodes were cytologically confirmed benign; in four patients, FNA was not possible or inconclusive. At a median postoperative follow-up of 15 months, only 1% of patients developed cervical lymph node metastases. This study shows no additional value of external ultrasonography to a negative PET-CT. According to our results, it can be omitted in the primary workup. However, suspect lymph nodes on PET-CT should be confirmed by FNA to exclude false positives if it would change treatment plan. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Clinical applications of sentinel lymph-node biopsy for the staging and treatment of solid neoplasms.

PubMed

Gipponi, M

2005-08-01

A review of the clinical applications of sentinel lymph node (sN) biopsy has been performed with the aim of defining the rationale, the methods of detection, the accuracy, and the current indications to sN biopsy in different solid neoplasms. In melanoma patients, sN biopsy represents a standard procedure for staging purpose, although its therapeutic value is still under examination. The sN is an accurate method for the pathologic staging of the axilla in patients with early stage breast cancer, and it can be useful for the selection of patients with axillary metastasis who should undergo standard axillary dissection. In gynecologic malignancies, appreciable results are available in patients with vulvar and cervical cancer only. Patients with squamous cell vulvar cancer may benefit by sN biopsy because a complete bilateral inguino-femoral lymph-node dissection may be avoided whenever the sN is free of metastasis. As regards to cervical cancer, further studies are required with the combined technique (blue dye injection and gamma-probe guided surgery), which seems more promising, before abandoning pelvic lymphadenectomy in patients with histologically-negative sN. The experience in urologic cancer deals mainly with penile and prostate cancer; the modern procedures for the dynamic detection of sN are going to clarify its role in the surgical management of penile cancer; as regards to prostate cancer, very preliminary results suggest that the sN biopsy may enhance the pathologic staging of this neoplasm compared to modified pelvic lymphadenectomy, due to the individual variability of the lymphatic drainage of this cancer. In patients with clinically node-negative squamous head and neck cancer, the reliability of sN-guided neck lymph node dissection seems promising. The sN biopsy is also technically feasible in patients with differentiated thyroid cancer; however, the future role of this procedure in the clinical decision-making of these patients remains to be defined due to the questionable biological meaning of nodal metastases. Patients with non-small-cell lung cancer should be investigated by means of radiotracers injected at the time of thoracotomy or under CT-scan guidance in order to achieve a satisfactory identification rate (over 80%); the focused histopathologic staging of the sN improves current pathologic staging by conventional bi-valve assessment of all the lymph nodes of the surgical specimen; moreover, the prognostic role of isolated N2 metastasis can be better elucidated. In patients with gastrointestinal malignancies, the intraoperative lymphatic mapping with sN biopsy have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent. In patients with gastric cancer, current data show that it can be detected by means of peritumoral injection of indocyanine green; the detection of tumor positive lymph nodes beyond the perigastric area could select patients amenable to D2 lymphadenectomy. As regards to colorectal cancer patients, the focused analysis of the sN may reveal disease that might otherwise go undetected by conventional surgical and pathological methods, and those patients which are upstaged can benefit by adjuvant chemotherapy. Finally, in patients with Merkel cell carcinoma, notwithstanding the limited experiences with sN biopsy, sN histology seems to predict regional lymph node status and may aid in selecting which patients are amenable to therapeutic lymph node dissection.

Sentinel Lymphadenectomy in Vulvar Cancer Using Near-Infrared Fluorescence From Indocyanine Green Compared With Technetium 99m Nanocolloid.

PubMed

Soergel, Philipp; Hertel, Hermann; Nacke, Anna Kaarina; Klapdor, Rüdiger; Derlin, Thorsten; Hillemanns, Peter

2017-05-01

Nowadays, sentinel diagnostic is performed using technetium 99m (Tc) nanocolloid as a radioactive marker and sometimes patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule that emits a light signal in the near-infrared band after excitation. Our study aimed to evaluate indocyanine green compared with the criterion-standard Tc-nanocolloid. We included patients with primary, unifocal vulvar cancer of less than 4 cm with clinically node-negative groins in this prospective trial. Sentinel diagnostic was carried out using Tc-nanocolloid, indocyanine green, and patent blue. We examined each groin for light signals from the near-infrared band, for radioactivity, and for blue staining. A sentinel lymph node was defined as a Tc-nanocolloid-positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested and then sent for histologic examination. In all, 27 patients were included in whom we found 91 sentinel lymph nodes in 52 groins. All these lymph nodes were positive for indocyanine green, also giving a sensitivity of 100% (95% confidence interval [CI], 96.0%-100%) compared with Tc-nanocolloid. Eight additional lymph nodes showed indocyanine green fluorescence but no Tc positivity, so that the positive predictive value was 91.9% (95% confidence interval, 84.6%-96.5%). In 1 patient, a false-negative sentinel missed by all 3 modalities was found. Our results show that indocyanine green is a promising approach for inguinal sentinel identification in vulvar cancer with a similar sensitivity as radioactive Tc-nanocolloid and worth to be evaluated in further studies.

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

[Management of penile cancer patients: new aspects of a rare tumour entity].

PubMed

Roiner, M; Maurer, O; Lebentrau, S; Gilfrich, C; Schäfer, C; Haberl, C; Brookman-May, S D; Burger, M; May, M; Hakenberg, O W

2018-06-01

Over the past few decades, some principles in the treatment of penile cancer have changed fundamentally. While 15 years ago a negative surgical margin of at least 2 cm was considered mandatory, organ-sparing surgery permitting minimal negative surgical margins has a high priority nowadays. The current treatment principle requires as much organ preservation as possible and as much radicality as necessary. The implementation of organ-sparing and reconstructive surgical techniques has improved the quality of life of surviving patients. However, oncological and functional outcomes are still unsatisfactory. Alongside with adequate local treatment of the primary tumour, a consistent management of inguinal lymph nodes is of fundamental prognostic significance. In particular, clinically inconspicuous inguinal lymph nodes staged T1b and upwards need a surgical approach. Sentinel node biopsy, minimally-invasive surgical techniques and modified inguinal lymphadenectomy have reduced morbidity compared to conventional inguinal lymph node dissection. Multimodal treatment with surgery and chemotherapy is required in all patients with lymph node-positive disease; neoadjuvant chemotherapy has been established for patients with locally advanced lymph node disease, and adjuvant treatment after radical inguinal lymphadenectomy for lymph node-positive disease. An increasing understanding of the underlying tumour biology, in particular the role of the human papilloma virus (HPV) and epidermal growth factor receptor (EGFR) status, has led to a new pathological classification and may further enhance treatment options. This review summarises current aspects in the therapeutic management of penile cancer. © Georg Thieme Verlag KG Stuttgart · New York.

Sentinel lymph node biopsy does not change melanoma-specific survival among patients with Breslow thickness greater than four millimeters.

PubMed

Caracò, Corrado; Celentano, Egidio; Lastoria, Secondo; Botti, Gerardo; Ascierto, Paolo Antonio; Mozzillo, Nicola

2004-03-01

Management of patients with cutaneous melanoma in the absence of lymph node metastases is still controversial. The experience at the National Cancer Institute in Naples was analyzed to evaluate 3-year disease-free survival and overall survival for all patients who underwent sentinel lymph node biopsy (SLB) with Breslow thickness greater than 4 mm. Data from 359 sentinel biopsies performed in the past 5 years were reviewed to determine the effect of the treatment on disease-free survival and overall survival after stratifying patients for node status, tumor ulceration, and Breslow thickness. Statistical analysis showed a better 3-year survival for sentinel node-negative patients than for sentinel node-positive cases (88.4% and 72.9%, respectively; P <.05). Tumor ulceration retained its prognostic significance despite lymph node status, indicating a higher risk for development of distant metastases. Survival curves associated with thicker melanomas did not show significant differences between negative- and positive-SLB patients. SLB provides accurate staging of nodal status in melanoma patients who have no clinical evidence of metastases. Longer follow-up and final results from ongoing trials are necessary to definitively clarify the role of this procedure.

Difference between observed and expected number of involved lymph nodes reflects the metastatic potential of breast cancer independent to intrinsic subtype.

PubMed

Yu, Ke-Da; Jiang, Yi-Zhou; Shao, Zhi-Ming

2015-06-30

Poor prognosis associated with metastasis in breast cancer patients highlights the critical need to develop an effective evaluation model for metastatic potential (MP). We hypothesized that MP could be also indicated by primary tumor size and involved lymph nodes (LNs). The expected number of involved LNs is defined as tumor size (cm) divided by 1.5. The effect of the surrogate for MP (defined as difference between the number of observed and expected involved LNs) on breast cancer-specific survival (BCSS) was investigated in the first cohort from SEER (n = 108,814). Validation was performed in another SEER cohort (n = 50,414) and a third cohort (n = 3,755). MP is an independent predictor for BCSS in the overall population [hazard ratio (HR) for high MP: 2.92; 95% confidence interval (CI): 2.80-3.03] and in subgroups. The effect of surrogate for MP on survival was independent to intrinsic subtype, with adjusted HRs of 3.46 (95%CI, 2.02-5.93), 2.30 (95%CI, 1.64-3.24), 4.05 (95%CI, 2.85-5.76), and 1.45 (95%CI, 1.04-2.03) in luminal-A, luminal-B, triple-negative, and HER2-positive subtypes, respectively. Difference between the observed and expected number of involved LNs serves as an indicator for MP, which is independent to intrinsic subtype and could predict survival. Our findings need further validation.

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.

Long-term outcomes among breast cancer patients with extensive regional lymph node involvement: implications for locoregional management.

PubMed

Braunstein, Lior Z; Galland-Girodet, Sigolene; Goldberg, Saveli; Warren, Laura E G; Sadek, Betro T; Shenouda, Mina N; Abi-Raad, Rita F; MacDonald, Shannon M; Taghian, Alphonse G

2015-12-01

Extensive lymph node (LN) involvement portends significant risk for distant metastasis (DM) among breast cancer patients. As a result, local management may be of secondary import to systemic control in this population. We analyzed patients with ≥10 involved LNs (N3) to evaluate the feasibility of breast conserving therapy (BCT) vs modified radical mastectomy (MRM) in this high-risk cohort. Among 98 women with N3 disease 46 (46.9%) underwent BCT and 52 (53.1%) received MRM. Nearly all patients (92%) received comprehensive radiotherapy (RT) including axillary and supraclavicular fields. The Kaplan-Meier method and Cox regression analyses were used to analyze time-to-event outcomes. Median follow-up was 76 months, with a 5-year DFS of 64.9% and OS of 71.9% among the cohort. Poorly differentiated (p = 0.007), ER-negative tumors (p = 0.015) had adverse DFS outcomes. Treatment groups did not differ with regard to 10-year DFS (45.4% for MRM vs. 57.6% for BCT; p = 0.31), or OS (61.4 vs. 63.7%; p = 0.79). DM-free survival was 48.9% following MRM and 60.6% following BCT (p = 0.19). Patients with ≥10 involved LNs have similar outcomes following BCT or MRM, suggesting that RT may obviate the need for more-extensive surgery. While local control is comparably favorable regardless of surgical approach, systemic control remains a challenge in this population.

Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.

PubMed

Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Persson, Jan

2018-03-01

To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer. Copyright © 2017. Published by Elsevier Inc.

Sentinel Lymph Node Biopsy: Quantification of Lymphedema Risk Reduction

DTIC Science & Technology

2006-10-01

dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J Radiat Oncol Biol Phys...techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast. Radiother Oncol. Feb...Harris JR. Three-dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J

Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer.

PubMed

Bains, S K; Peters, A M; Zammit, C; Ryan, N; Ballinger, J; Glass, D M; Allen, S; Stanton, A W B; Mortimer, P S; Purushotham, A D

2015-04-01

Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL. Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. ISRCTN84866416 ( http://www.isrctn.com). © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Anti-Heat Shock Protein-27 Antibody Levels in Women with Breast Cancer: Association with Disease Complications and Two-Year Disease-Free Survival

PubMed Central

Homaei-Shandiz, Fatemeh; Mehrad-Majd, Hassan; Tasbandi, Mojtaba; Aledavood, Amir; Afshari, Jalil Tavakol; Ghavami, Vahid; Ghayour-Mobarhan, Majid

2016-01-01

Background and Aim: Breast cancer is a major healthcare problem in women. There are many reports about up-regulation of Hsp27 in cancer tissues but less is known about the potential relationship between Hsp27 antibody levels and breast cancer complications. We here investigated concentrations of serum Hsp27 antigen and antibodies in subjects with and without breast cancer and assessed potential associations with two-year disease-free survival, histological grade and number of lymph nodes. Materials and Methods: Specifically, serum Hsp27 antigen and antibody levels from 97 patients with breast cancer, and 65 healthy controls were determined by enzyme-linkedimmunosorbent assays (ELISAs). Results: Serum Hsp27 and antibody levels were significantly (p<0.001) higher in patients with breast cancer compared to the control group, but no relationship were found with two-year disease free survival, histological grade or number of lymph nodes (p> 0.6, 0.2 and 0.9 respectively). Conclusions: Elevated levels of Hsp27 antibody occur with women with breast cancer but do not appear to be associated with the presence of disease clinical complications. PMID:27892679

[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.

Effectiveness of the Benign and Malignant Diagnosis of Mediastinal and Hilar Lymph Nodes by Endobronchial Ultrasound Elastography.

PubMed

Huang, Haidong; Huang, Zhiang; Wang, Qin; Wang, Xinan; Dong, Yuchao; Zhang, Wei; Zarogoulidis, Paul; Man, Yan-Gao; Schmidt, Wolfgang Hohenforst; Bai, Chong

2017-01-01

Background and Objectives: Endobronchial ultrasound elastography is a new technique for describing the stiffness of tissue during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The aims of this study were to investigate the diagnostic value of Endobronchial ultrasound (EBUS) elastography for distinguishing the difference between benign and malignant lymph nodes among mediastinal and hilar lymph node. Materials and Methods: From June 2015 to August 2015, 47 patients confirmed of mediastinal and hilar lymph node enlargement through examination of Computed tomography (CT) were enrolled, and a total of 78 lymph nodes were evaluated by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). EBUS-guided elastography of lymph nodes was performed prior to EBUS-TBNA. A convex probe EBUS was used with a new EBUS processor to assess elastographic patterns that were classified based on color distribution as follows: Type 1, predominantly non-blue (green, yellow and red); Type 2, part blue, part non-blue (green, yellow and red); Type 3, predominantly blue. Pathological determination of malignant or benign lymph nodes was used as the gold standard for this study. The elastographic patterns were compared with the final pathologic results from EBUS-TBNA. Results: On pathological evaluation of the lymph nodes, 45 were benign and 33 were malignant. The lymph nodes that were classified as Type 1 on endobronchial ultrasound elastography were benign in 26/27 (96.3%) and malignant in 1/27 (3.7%); for Type 2 lymph nodes, 15/20 (75.0%) were benign and 5/20 (25.0%) were malignant; Type 3 lymph nodes were benign in 4/31 (12.9%) and malignant in 27/31 (87.1%). In classifying Type 1 as 'benign' and Type 3 as 'malignant,' the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rates were 96.43%, 86.67%, 87.10%, 96.30%, 91.38%, respectively. Conclusion: EBUS elastography of mediastinal and hilar lymph nodes is a noninvasive technique that can be performed reliably and may be helpful in the prediction of benign and malignant lymph nodes among mediastinal and hilar lymph node during EBUS-TBNA.

The added value of a portable gamma camera for intraoperative detection of sentinel lymph node in squamous cell carcinoma of the oral cavity: A case report.

PubMed

Mayoral, M; Paredes, P; Sieira, R; Vidal-Sicart, S; Marti, C; Pons, F

2014-01-01

The use of sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity is still subject to debate although some studies have reported its feasibility. The main reason for this debate is probably due to the high false-negative rate for floor-of-mouth tumors per se. We report the case of a 54-year-old man with a T1N0 floor-of-mouth squamous cell carcinoma who underwent the sentinel lymph node procedure. Lymphoscintigraphy and SPECT/CT imaging were performed for lymphatic mapping with a conventional gamma camera. Sentinel lymph nodes were identified at right Ib, left IIa and Ia levels. However, these sentinel lymph nodes were difficult to detect intraoperatively with a gamma probe owing to the activity originating from the injection site. The use of a portable gamma camera made it possible to localize and excise all the sentinel lymph nodes. This case demonstrates the usefulness of this tool to improve sentinel lymph node detecting in floor-of-mouth tumors, especially those close to the injection area. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

[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.

[Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report].

PubMed

Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Alonso-Briones, Marco Vinicio; Trujillo-de Anda, Ana Patricia

2013-01-01

breast metaplastic carcinomas are a heterogeneous group of neoplasms that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond less than 1% of all malignant neoplasms of the mammary gland. They usually present as high-grade tumors with a lower rate of lymph node metastases and decreased expression of estrogen and progesterone receptors and Her2 and increased expression of Her1 and Ki-67. we report a 52 year old woman with a breast carcinosarcoma presented with a left breast tumor fungated, ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at diagnosis. She received multimodal management with neoadjuvant chemotherapy, followed by mastectomy and adjuvant chemotherapy; she presented progression of the disease with lung metastases and local massive recurrence, eventually died from complications associated to the disease. metaplastic carcinomas of the breast are extremely rare entities. Due the nature of disease and presentation, the prognosis is poor in these patients. There are several histologic subtypes based on studies of hematoxylin and eosin and immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy and chemotherapy) for best results.

One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer.

PubMed

Fanfani, Francesco; Monterossi, Giorgia; Ghizzoni, Viola; Rossi, Esther D; Dinoi, Giorgia; Inzani, Frediano; Fagotti, Anna; Gueli Alletti, Salvatore; Scarpellini, Francesca; Nero, Camilla; Santoro, Angela; Scambia, Giovanni; Zannoni, Gian F

2018-01-01

The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC). From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides. Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found. The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.

Case report of metastatic invasive breast lobular carcinoma to the urinary bladder.

PubMed

Al Ibraheemi, Ahmed A

2016-01-01

Breast cancer is the most common cancer in women except skin cancer. The common metastatic sites include lymph node, lung, liver and bone. However, metastasis to the bladder is extremely rare. To our knowledge, this is the first case of breast cancer metastasis to urinary bladder in Jordan which is reported. Nine years after the initial diagnosis of lobular breast carcinoma, the patient suffered from left side leg edema; Ultrasonography and Computed tomography scanning showed thickening of posterior bladder wall and bilateral hydronephrosis. The biopsy of the bladder confirmed metastatic lesion from the breast. In contrast to the primary tumor, bladder metastasis showed negative expression of estrogen (ER) and progesterone (PR) receptors. However, Her2neu test was negative in both. The reported case confirms that bladder metastasis from breast cancer tend to occur late after the diagnosis of the primary tumor. Furthermore, bladder metastasis can be asymptomatic and heterogeneous in ER and PR expression in comparison with the primary tumor. This report supports the need for careful follow-up and early intervention whenever such clinical situation is suspected. This report supports further evaluation of receptor status at time of metastasis.

[18F]FDG imaging of head and neck tumours: comparison of hybrid PET and morphological methods.

PubMed

Dresel, S; Grammerstorff, J; Schwenzer, K; Brinkbäumer, K; Schmid, R; Pfluger, T; Hahn, K

2003-07-01

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose ([(18)F]FDG) imaging of head and neck tumours using a second- or third-generation hybrid PET device. Results were compared with the findings of spiral computed tomography (CT) and magnetic resonance imaging (MRI), and, as regards lymph node metastasis, the ultrasound findings. A total of 116 patients with head and neck tumours (83 males and 33 females aged 27-88 years) were examined using a hybrid PET scanner after injection of 185-350 MBq of [(18)F]FDG (Picker Prism 2000 XP-PCD, Marconi Axis gamma-PET(2) AZ). Hybrid PET examinations were performed in list mode using an axial filter. Reconstruction of data was performed iteratively. Ninety-six patients underwent CT using a multislice technique (Siemens Somatom Plus 4, Marconi MX 8000), 18 patients underwent MRI and 100 patients were examined by ultrasound. All findings were verified by histology, which was considered the gold standard, or, in the event of negative histology, by follow-up. Correct diagnosis of the primary or recurrent lesion was made in 73 of 85 patients using the hybrid PET scanner, in 50 of 76 patients on CT and in 7 of 10 patients on MRI. Hybrid PET successfully visualised metastatic disease in cervical lymph nodes in 28 of 34 patients, while 23 of 31 were correctly diagnosed with CT, 3 of 4 with MRI and 30 of 33 with ultrasound. False positive results regarding lymph node metastasis were seen in three patients with hybrid PET, in 14 patients with CT and in 13 patients with ultrasound. MRI yielded no false positive results concerning lymph node metastasis. In one patient, unrecognised metastatic lesions were seen on hybrid PET elsewhere in the body (lung: n=1; bone: n=1). Additional malignant lesions at sites other than the head and neck tumour were found in three patients (one patient with lung cancer, one patient with pelvic metastasis due to a carcinoma of the prostate and one patient with pulmonary metastasis due to breast cancer). It is concluded that [(18)F]FDG PET with hybrid PET scanners is superior to CT and MRI in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement, whereas it is inferior to ultrasound in the detection of cervical lymph node metastasis.

Optical biopsy of lymph node morphology using optical coherence tomography.

PubMed

Luo, Wei; Nguyen, Freddy T; Zysk, Adam M; Ralston, Tyler S; Brockenbrough, John; Marks, Daniel L; Oldenburg, Amy L; Boppart, Stephen A

2005-10-01

Optical diagnostic imaging techniques are increasingly being used in the clinical environment, allowing for improved screening and diagnosis while minimizing the number of invasive procedures. Diffuse optical tomography, for example, is capable of whole-breast imaging and is being developed as an alternative to traditional X-ray mammography. While this may eventually be a very effective screening method, other optical techniques are better suited for imaging on the cellular and molecular scale. Optical Coherence Tomography (OCT), for instance, is capable of high-resolution cross-sectional imaging of tissue morphology. In a manner analogous to ultrasound imaging except using optics, pulses of near-infrared light are sent into the tissue while coherence-gated reflections are measured interferometrically to form a cross-sectional image of tissue. In this paper we apply OCT techniques for the high-resolution three-dimensional visualization of lymph node morphology. We present the first reported OCT images showing detailed morphological structure and corresponding histological features of lymph nodes from a carcinogen-induced rat mammary tumor model, as well as from a human lymph node containing late stage metastatic disease. The results illustrate the potential for OCT to visualize detailed lymph node structures on the scale of micrometastases and the potential for the detection of metastatic nodal disease intraoperatively.

Magnetic Resonance Lymphography Findings in Patients With Biochemical Recurrence After Prostatectomy and the Relation With the Stephenson Nomogram

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

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Debats, Oscar A.; Roach, Mack

2012-12-01

Purpose: To estimate the occurrence of positive lymph nodes on magnetic resonance lymphography (MRL) in patients with a prostate-specific antigen (PSA) recurrence after prostatectomy and to investigate the relation between score on the Stephenson nomogram and lymph node involvement on MRL. Methods and Materials: Sixty-five candidates for salvage radiation therapy were referred for an MRL to determine their lymph node status. Clinical and histopathologic features were recorded. For 49 patients, data were complete to calculate the Stephenson nomogram score. Receiver operating characteristic (ROC) analysis was performed to determine how well this nomogram related to the MRL result. Analysis was donemore » for the whole group and separately for patients with a PSA <1.0 ng/mL to determine the situation in candidates for early salvage radiation therapy, and for patients without pathologic lymph nodes at initial lymph node dissection. Results: MRL detected positive lymph nodes in 47 patients. ROC analysis for the Stephenson nomogram yielded an area under the curve (AUC) of 0.78 (95% confidence interval, 0.61-0.93). Of 29 patients with a PSA <1.0 ng/mL, 18 had a positive MRL. Of 37 patients without lymph node involvement at initial lymph node dissection, 25 had a positive MRL. ROC analysis for the Stephenson nomogram showed AUCs of 0.84 and 0.74, respectively, for these latter groups. Conclusion: MRL detected positive lymph nodes in 72% of candidates for salvage radiation therapy, in 62% of candidates for early salvage radiation therapy, and in 68% of initially node-negative patients. The Stephenson nomogram showed a good correlation with the MRL result and may thus be useful for identifying patients with a PSA recurrence who are at high risk for lymph node involvement.« less

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

Sentinel lymph node mapping in melanoma: the issue of false-negative findings.

PubMed

Manca, Gianpiero; Rubello, Domenico; Romanini, Antonella; Boni, Giuseppe; Chiacchio, Serena; Tredici, Manuel; Mazzarri, Sara; Duce, Valerio; Colletti, Patrick M; Volterrani, Duccio; Mariani, Giuliano

2014-07-01

Management of cutaneous melanoma has changed after introduction in the clinical routine of sentinel lymph node biopsy (SLNB) for nodal staging. By defining the nodal basin status, SLNB provides a powerful prognostic information. Nevertheless, some debate still surrounds the accuracy of this procedure in terms of false-negative rate. Several large-scale studies have reported a relatively high false-negative rate (5.6%-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. In this review, we identified all the technical aspects that the nuclear medicine physician, the surgeon, and the pathologist should take into account to improve accuracy of the procedure and minimize the false-negative rate. In particular, SPECT/CT imaging detects more SLNs than those found by planar lymphoscintigraphy. Furthermore, the nuclear medicine community should reach a consensus on the radioactive counting rate threshold to better guide the surgeon in identifying the lymph nodes with the highest likelihood of housing metastases ("true biologic SLNs"). Analysis of the harvested SLNs by conventional techniques is also a further potential source for error. More accurate SLN analysis (eg, molecular analysis by reverse transcriptase-polymerase chain reaction) and more extensive SLN sampling identify more positive nodes, thus reducing the false-negative rate.The clinical factors identifying patients at higher-risk local recurrence after a negative SLNB include older age at diagnosis, deeper lesions, histological ulceration, and head-neck anatomic location of the primary lesion.The clinical impact of a false-negative SLNB on the prognosis of melanoma patients remains controversial, because the majority of studies have failed to demonstrate overall statistically significant disadvantage in melanoma-specific survival for false-negative SLNB patients compared with true-positive SLNB patients.When new more effective drugs will be available in the adjuvant setting for stage III melanoma patients, the implication of an accurate staging procedure for the sentinel lymph nodes will be crucial for both patients and clinicians. Standardization and accuracy of SLN identification, removal, and analysis are required.

A critical reappraisal of false negative sentinel lymph node biopsy in melanoma.

PubMed

Manca, G; Romanini, A; Rubello, D; Mazzarri, S; Boni, G; Chiacchio, S; Tredici, M; Duce, V; Tardelli, E; Volterrani, D; Mariani, G

2014-06-01

Lymphatic mapping and sentinel lymph node biopsy (SLNB) have completely changed the clinical management of cutaneous melanoma. This procedure has been accepted worldwide as a recognized method for nodal staging. SLNB is able to accurately determine nodal basin status, providing the most useful prognostic information. However, SLNB is not a perfect diagnostic test. Several large-scale studies have reported a relatively high false-negative rate (5.6-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. The main purpose of this review is to address the technical issues that nuclear physicians, surgeons, and pathologists should carefully consider to improve the accuracy of SLNB by minimizing its false-negative rate. In particular, SPECT/CT imaging has demonstrated to be able to identify a greater number of sentinel lymph nodes (SLNs) than those found by planar lymphoscintigraphy. Furthermore, a unique definition in the international guidelines is missing for the operational identification of SLNs, which may be partly responsible for this relatively high false-negative rate of SLNB. Therefore, it is recommended for the scientific community to agree on the radioactive counting rate threshold so that the surgeon can be better radioguided to detect all the lymph nodes which are most likely to harbor metastases. Another possible source of error may be linked to the examination of the harvested SLNs by conventional histopathological methods. A more careful and extensive SLN analysis (e.g. molecular analysis by RT-PCR) is able to find more positive nodes, so that the false-negative rate is reduced. Older age at diagnosis, deeper lesions, histologic ulceration, head-neck anatomical location of primary lesions are the clinical factors associated with false-negative SLNBs in melanoma patients. There is still much controversy about the clinical significance of a false-negative SLNB on the prognosis of melanoma patients. Indeed, most studies have failed to show that there is worse melanoma-specific survival for false-negative compared to true-positive SLNB patients.

Sentinel lymph node mapping in breast cancer: a critical reappraisal of the internal mammary chain issue.

PubMed

Manca, G; Volterrani, D; Mazzarri, S; Duce, V; Svirydenka, A; Giuliano, A; Mariani, G

2014-06-01

Although, like the axilla, the internal mammary nodes (IMNs) are a first-echelon nodal drainage site in breast cancer, the importance of their treatment has long been debated. Seminal randomized trials have failed to demonstrate a survival benefit from surgical IMN dissection, and several retrospective studies have shown that IMNs are rarely the first site of recurrence. However, the recent widespread adoption of sentinel lymph node (SLN) biopsy has stimulated a critical reappraisal of such early results. Furthermore, the higher proportion of screening-detected cancers, improved imaging and techniques (i.e., lymphoscintigraphy for radioguided SLN biopsy) make it possible to visualize lymphatic drainage to the IMNs. The virtually systematic application of adjuvant systemic and/or loco-regional radiotherapy encourages re-examination of the significance of IMN metastases. Moreover, randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic chemotherapy, which was not routinely administered in the earlier studies. However, the contribution from IMN treatment is unclear. Lymphoscintigraphic studies have shown that a significant proportion of breast cancers have primary drainage to the IMNs, including approximately 30% of medial tumors and 15% of lateral tumors. In the few studies where IMN biopsy was performed, 20% of sentinel IMNs were metastatic. The risk of IMN involvement is higher in patients with medial tumors and positive axillary nodes. IMN metastasis has prognostic significance, as recognized by its inclusion in the American Joint Committee on Cancer staging criteria, and seems to have similar prognostic importance as axillary nodal involvement. Although routine IMN evaluation might be indicated, it has not been routinely performed, perhaps because IMN drainage with lymphoscintigraphy is more difficult to demonstrate than axillary drainage. This difference is due to technical reasons and not the absence of lymphatics to the IMN. Recent anatomical studies have confirmed a model of breast lymphatic drainage that comprises superficial, deep and perforating systems. The superficial system drains to the axilla, usually to a lymph node posterior to the pectoralis minor muscle. The deep system drains to the axilla and also anastomoses with the perforating system which drains to the IMNs. The perforating system does not connect with the superficial system. The prevalence of IMN drainage tends to reflect the method of lymphoscintigraphy, where peritumoral (deep lymphatic system) injections have a much higher likelihood of IMN drainage than subareolar or subdermal (superficial lymphatic system) injections. The fused SPECT/CT images represent a further technical solution to increase the identification of IMNs and consequently can significantly reduce the false negative rate of sentinel lymph node biopsy. Before mature results from current and future randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy and IMNs biopsy may be used to guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity.

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

Gentile, Michelle S.; Usman, Asad A.; Neuschler, Erin I.

Purpose: The purpose of this study was to identify the axillary lymph nodes on pretreatment diagnostic computed tomography (CT) of the chest to determine their position relative to the anatomic axillary borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Methods and Materials: Pretreatment diagnostic CT chest scans available for 30 breast cancer patients with clinically involved lymph nodes were fused with simulation CT. Contouring of axillary levels I, II, and III according to the RTOG guidelines was performed. Measurements were made from the area of distal tumor to the anatomic bordersmore » in 6 dimensions for each level. Results: Of the 30 patients, 100%, 93%, and 37% had clinical involvement of levels I, II, and III, respectively. The mean number of lymph nodes dissected was 13.6. The mean size of the largest lymph node was 2.4 cm. Extracapsular extension was seen in 23% of patients. In 97% of patients, an aspect of the involved lymph node lay outside of the anatomic border of a level. In 80% and 83% of patients, tumor extension was seen outside the cranial (1.78 ± 1.0 cm; range, 0.28-3.58 cm) and anterior (1.27 ± 0.92 cm; range, 0.24-3.58 cm) borders of level I, respectively. In 80% of patients, tumor extension was seen outside the caudal border of level II (1.36 ± 1.0 cm, range, 0.27-3.86 cm), and 0% to 33% of patients had tumor extension outside the remaining borders of all levels. Conclusions: To cover 95% of lymph nodes at the cranial and anterior borders of level I, an additional clinical target volume margin of 3.78 cm and 3.11 cm, respectively, is necessary. The RTOG guidelines may be insufficient for coverage of axillary disease in patients with clinical nodal involvement who are undergoing neoadjuvant chemotherapy, incomplete axillary dissection, or treatment with intensity modulated radiation therapy. In patients with pretreatment diagnostic CT chest scans, fusion with simulation CT should be considered for tumor delineation.« less

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.

Photo-guided sentinel node mapping in breast cancer using marker-free photo-gamma fusion lymphoscintigraphy.

PubMed

Lee, Eun Seong; Chun, In Kook; Ha, Seunggyun; Yoon, Hai-Jeon; Jung, So-Youn; Lee, Seeyoun; Kim, Seok Won; Lee, Eun Sook; Kim, Taeyoon; Kim, Kwang Gi; Lee, Byung Il; Kim, Tae Sung; Kim, Seok-Ki

2013-03-01

Photo-gamma fusion lymphoscintigraphy (PGFLS) was developed by overlying a conventional planar gamma image on a photograph for the guidance of sentinel node biopsy. The feasibility and accuracy of PGFLS was assessed in breast cancer patients. A digital camera and a gamma camera were coordinated to obtain photograph and gamma images from the same angle. Using the distance to the object and calibration acquisition with a flat phantom and radioactive markers, PGFLS was performed both in phantom and in patients without fiducial markers. Marker-free PGFLS was verified using flat phantom, anthropomorphic phantom with markers simulating sentinel nodes and breast cancer patients. In addition, the depth of the radioactive marker or sentinel node was calculated using two gamma images taken at right angles. The feasibility and accuracy of PGFLS were assessed in terms of mismatch errors of co-registration and depth with reference to the data from SPECT/CT. The mismatch error was less than 6 mm in the flat phantom image at a distance from 50 to 62 cm without misalignment. In the anthropomorphic phantom study, co-registration error was 0.42 ± 0.29 cm; depth error was 0.51 ± 0.37 cm, which was well correlated with the reference value on SPECT/CT (x scale: R(2) = 0.99, p < 0.01; y scale: R(2) = 0.99, p < 0.01; depth: R(2) = 0.99, p < 0.01). In ten patients with breast cancer referred for lympho-SPECT/CT, PGFSL enabled photo-guided sentinel lymph node mapping with acceptable accuracy (co-registration error, 0.47 ± 0.24 cm; depth error, 1.20 ±0.41 cm). The results from PGFSL showed close correlation with those from SPECT/CT (x scale: R(2) = 0.99, p < 0.01; y scale: R(2) = 0.98, p < 0.01; depth: R(2) = 0.77, p < 0.01). The novel and convenient PGFLS technique is clinically feasible, showing acceptable accuracy and providing additional visual and quantitative information for sentinel lymph node mapping. This approach will facilitate photo-guided sentinel lymph node dissection in breast cancer.

[The clinical value of sentinel lymph node detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck by methylene blue method and radiolabeled tracer method].

PubMed

Zhao, Xin; Xiao, Dajiang; Ni, Jianming; Zhu, Guochen; Yuan, Yuan; Xu, Ting; Zhang, Yongsheng

2014-11-01

To investigate the clinical value of sentinel lymph node (SLN) detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck (cN0) by methylene blue method, radiolabeled tracer method and combination of these two methods. Thirty-three patients with cN0 laryngeal carcinoma and six patients with cN0 hypopharyngeal carcinoma underwent SLN detection using both of methylene blue and radiolabeled tracer method. All these patients were accepted received the injection of radioactive isotope 99 Tc(m)-sulfur colloid (SC) and methylene blue into the carcinoma before surgery, then all these patients underwent intraopertive lymphatic mapping with a handheld gamma-detecting probe and blue-dyed SLN. After the mapping of SLN, selected neck dissections and tumor resections were peformed. The results of SLN detection by radiolabeled tracer, dye and combination of both methods were compared. The detection rate of SLN by radiolabeled tracer, methylene blue and combined method were 89.7%, 79.5%, 92.3% respectively. The number of detected SLN was significantly different between radiolabeled tracer method and combined method, and also between methylene blue method and combined method. The detection rate of methylene blue and radiolabeled tracer method were significantly different from combined method (P < 0.05). Nine patients were found to have lymph node metastasis by final pathological examination. The accuracy and negative rate of SLN detection of the combined method were 97.2% and 11.1%. The combined method using radiolabeled tracer and methylene blue can improve the detection rate and accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately represent the cervical lymph node status in cN0 laryngeal and hypopharyngeal carcinoma.

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.

Radiographic findings after treatment with balloon brachytherapy accelerated partial breast irradiation.

PubMed

Ibrahim, Nafisa B; Anandan, Srividya; Hartman, Audrey L; McSweeney, Michelle; Chun, Jeanette; McKee, Andrea; Yang, Rebecca; Kim, Cathleen

2015-01-01

The use of accelerated partial breast irradiation (APBI) following breast-conserving surgery is rapidly gaining popularity as an alternative to whole-breast irradiation (WBI) in selected patients with early-stage breast cancer. Although data on the long-term effectiveness and safety of APBI accelerated partial breast irradiation are still being gathered, the shorter treatment course and narrowed radiation target of APBI accelerated partial breast irradiation provide an attractive alternative for carefully selected patients. These patients include those with relatively small tumors (≤3 cm), negative or close margins, and negative sentinel lymph nodes. Possible long-term complications include telangiectasia and the development of a palpable mass at the lumpectomy site. Mammographic findings in patients who have undergone APBI accelerated partial breast irradiation are distinct from those in patients who have undergone conventional WBI whole-breast irradiation . The most common post-APBI accelerated partial breast irradiation radiographic findings include formation of seromas at the lumpectomy site, focal parenchymal changes such as increased trabeculation and parenchymal distortion, fat necrosis, and skin changes such as thickening or retraction. Given the continued evolution of breast cancer treatment, it is important that radiologists have a comprehensive understanding of APBI accelerated partial breast irradiation in terms of rationale, patient selection criteria, common postprocedural radiographic findings (and how they differ from post-WBI whole-breast irradiation findings), and advantages and potential complications. RSNA, 2015

Cat scratch disease and lymph node tuberculosis in a colon patient with cancer.

PubMed

Matias, M; Marques, T; Ferreira, M A; Ribeiro, L

2013-12-12

A 71-year-old man operated for a sigmoid tumour remained in the surveillance after adjuvant chemotherapy. After 3 years, a left axillary lymph node was visible on CT scan. The biopsy revealed a necrotising and abscessed granulomatous lymphadenitis, suggestive of cat scratch disease. The patient confirmed having been scratched by a cat and the serology for Bartonella henselae was IgM+/IgG-. Direct and culture examinations for tuberculosis were negative. The patient was treated for cat scratch disease. One year later, the CT scan showed increased left axillary lymph nodes and a left pleural effusion. Direct and cultural examinations to exclude tuberculosis were again negative. Interferon-γ release assay testing for tuberculosis was undetermined and then positive. Lymph node and pleural tuberculosis were diagnosed and treated with a good radiological response. This article has provides evidence of the importance of continued search for the right diagnosis and that two diagnoses can happen in the same patient.

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

Portable real-time optical coherence tomography system for intraoperative imaging and staging of breast cancer

NASA Astrophysics Data System (ADS)

Nguyen, Freddy T.; Zysk, Adam M.; Kotynek, Jan G.; Bellafiore, Frank J.; Rowland, Kendrith M.; Johnson, Patricia A.; Chaney, J. Eric; Boppart, Stephen A.

2007-02-01

Breast cancer continues to be one of the most widely diagnosed forms of cancer amongst women and the second leading type of cancer deaths amongst women. The recurrence rate of breast cancer is highly dependent on several factors including the complete removal of the primary tumor and the presence of cancer cells in involved lymph nodes. The metastatic spread and staging of breast cancer is also evaluated through the nodal assessment of the regional lymphatic system. A portable real-time spectral domain optical coherence tomography system is being presented as a clinical diagnostic tool in the intraoperative delineation of tumor margins as well as for real time lymph node assessment. The system employs a super luminescent diode centered at 1310 nm with a bandwidth of 92 nm. Using a spectral domain detection system, the data is acquired at a rate of 5 KHz / axial scan. The sample arm is a galvanometer scanning telecentric probe with an objective lens (f = 60 mm, confocal parameter = 1.5 mm) yielding an axial resolution of 8.3 μm and a transverse resolution of 35.0 μm. Images of tumor margins are acquired in the operating room ex vivo on freshly excised human tissue specimen. This data shows the potential of the use of OCT in defining the structural tumor margins in breast cancer. Images taken from ex-vivo samples on the bench system clearly delineate the differences between clusters of tumor cells and nearby adipose cells. In addition, the data shows the potential for OCT as a diagnostic tool in the staging of cancer metastasis through locoregional lymph node assessment.

The efficacy of physiotherapy upon shoulder function following axillary dissection in breast cancer, a randomized controlled study

PubMed Central

Beurskens, Carien HG; van Uden, Caro JT; Strobbe, Luc JA; Oostendorp, Rob AB; Wobbes, Theo

2007-01-01

Background Many patients suffer from severe shoulder complaints after breast cancer surgery and axillary lymph node dissection. Physiotherapy has been clinically observed to improve treatment of these patients. However, it is not a standard treatment regime. The purpose of this study is to investigate the efficacy of physiotherapy treatment of shoulder function, pain and quality of life in patients who have undergone breast cancer surgery and axillary lymph node dissection. Methods Thirty patients following breast cancer surgery and axillary lymph node dissection were included in a randomised controlled study. Assessments were made at baseline and after three and six months. The treatment group received standardised physiotherapy treatment of advice and exercises for the arm and shoulder for three months; the control group received a leaflet containing advice and exercises. If necessary soft tissue massage to the surgical scar was applied. Primary outcome variables were amount of pain in the shoulder/arm recorded on the Visual Analogue Scale, and shoulder mobility (flexion, abduction) measured using a digital inclinometer under standardized conditions. Secondary outcome measures were shoulder disabilities during daily activities, edema, grip strength of both hands and quality of life. The researcher was blinded to treatment allocation. Results All thirty patients completed the trial. After three and six months the treatment group showed a significant improvement in shoulder mobility and had significantly less pain than the control group. Quality of life improved significantly, however, handgrip strength and arm volume did not alter significantly. Conclusion Physiotherapy reduces pain and improves shoulder function and quality of life following axillary dissection after breast cancer. Trial registration ISRCTN31186536 PMID:17760981

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

The use of artificial intelligence technology to predict lymph node spread in men with clinically localized prostate carcinoma.

PubMed

Crawford, E D; Batuello, J T; Snow, P; Gamito, E J; McLeod, D G; Partin, A W; Stone, N; Montie, J; Stock, R; Lynch, J; Brandt, J

2000-05-01

The current study assesses artificial intelligence methods to identify prostate carcinoma patients at low risk for lymph node spread. If patients can be assigned accurately to a low risk group, unnecessary lymph node dissections can be avoided, thereby reducing morbidity and costs. A rule-derivation technology for simple decision-tree analysis was trained and validated using patient data from a large database (4,133 patients) to derive low risk cutoff values for Gleason sum and prostate specific antigen (PSA) level. An empiric analysis was used to derive a low risk cutoff value for clinical TNM stage. These cutoff values then were applied to 2 additional, smaller databases (227 and 330 patients, respectively) from separate institutions. The decision-tree protocol derived cutoff values of < or = 6 for Gleason sum and < or = 10.6 ng/mL for PSA. The empiric analysis yielded a clinical TNM stage low risk cutoff value of < or = T2a. When these cutoff values were applied to the larger database, 44% of patients were classified as being at low risk for lymph node metastases (0.8% false-negative rate). When the same cutoff values were applied to the smaller databases, between 11 and 43% of patients were classified as low risk with a false-negative rate of between 0.0 and 0.7%. The results of the current study indicate that a population of prostate carcinoma patients at low risk for lymph node metastases can be identified accurately using a simple decision algorithm that considers preoperative PSA, Gleason sum, and clinical TNM stage. The risk of lymph node metastases in these patients is < or = 1%; therefore, pelvic lymph node dissection may be avoided safely. The implications of these findings in surgical and nonsurgical treatment are significant.

Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping

NASA Astrophysics Data System (ADS)

B. Mondal, Suman; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P.; Liang, Kexian; Som, Avik; Akers, Walter J.; Fields, Ryan C.; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

2015-07-01

The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging.

Prognostic Value of Occult Isolated Tumour Cells within Regional Lymph Nodes of Dogs with Malignant Mammary Tumours.

PubMed

Coleto, A F; Wilson, T M; Soares, N P; Gundim, L F; Castro, I P; Guimarães, E C; Bandarra, M B; Medeiros-Ronchi, A A

2018-01-01

Canine mammary tumours (CMTs) are the most common type of neoplasm in bitches. As in women, the presence of metastasis in regional lymph nodes is an important prognostic factor in bitches with mammary carcinomas, but the clinical significance of occult isolated tumour cells (ITCs) within lymph nodes is still undefined in this species. The effectiveness of immunohistochemistry (IHC) in identifying occult ITCs and micrometastasis (MIC) was compared with that of the conventional haematoxylin and eosin staining technique. The relationship between tumour size, histological type, histological grade and the presence of metastasis was evaluated. The overall survival (OS) of female dogs with occult mammary carcinomas and ITCs within lymph nodes was analysed. Fragments of mammary carcinoma and regional lymph nodes of 59 female dogs were also evaluated. Histological sections of mammary carcinoma and lymph node samples were studied for tumour diagnosis and lymph node samples were tested by IHC using a pan-cytokeratin antibody. It was found that 35.2% of occult ITCs and 2.8% of hidden MIC were detected when IHC was used. There was a good correlation between the size of the tumour and metastasis to the lymph nodes (P = 0.77). ITCs were observed more frequently in the medullary region (60.7%) and metastases in the cortical region (44.4%). There was no significant difference in the OS between female dogs with occult ITCs and lymph nodes without ITCs. IHC can detect occult tumour cells in lymph nodes that are negative by histopathological examination. Female dogs with nodal ITCs do not have lower survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

Technique for reliable sentinel node biopsy in squamous cell carcinomas of the floor of mouth.

PubMed

Stoeckli, Sandro J; Huebner, Thomas; Huber, Gerhard F; Broglie, Martina A

2016-09-01

Applicability of sentinel node biopsy (SNB) for tumors of the floor of mouth (FOM) is controversial. Prospective evaluation of the accuracy of gamma-probe-guided superselective neck dissection of the preglandular triangle of level I for SNB in FOM squamous cell carcinoma (SCC) after preoperative lymphoscintigraphy and single photon emission CT (SPECT)/CT. In total, 22 sentinel lymph nodes were harvested in level I. Eight of 22 (36%) were seen on lymphoscintigraphy and 11 (50%) on SPECT/CT. Eleven sentinel lymph nodes (50%) were only detected intraoperatively. In unilateral tumors, 20% were contralateral, and, in midline tumors, 93% showed bilateral level I sentinel lymph nodes. The false-negative rate was 8.3%, the negative predictive value was 96.4%, and the false-omission rate was 3.6%. The ultimate neck control rate, including salvage treatment, was 100%. SNB in FOM can be reliably performed using the presented surgical technique. Level I exploration, bilaterally in midline tumors, is mandatory irrespective of the visualization of sentinel lymph nodes in other levels. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1367-1372, 2016. © 2016 Wiley Periodicals, Inc.

Time to Redefine the Intramammary Lymph Node as a Separate Entity?

PubMed

Green, M; Tafazal, H; Swati, B; Vidya, R

2018-04-17

The lymphatic drainage for the majority of primary breast tumours is to the axillary lymph nodes (ALNs). Some, however drain to the so-called extra-axillary basins, namely the internal mammary, supra- and infraclavicular regions. Another potential drainage route includes the intramammary lymph nodes (IMLNs). Current guidance suggests IMLNs should be considered as part of the axillary group, potentially affecting axillary management. However, due to evolution in imaging and advancement in technology, IMLNs may now be distinguished more accurately pre-operatively. There are currently no published guidelines for the management of IMLNs in the United Kingdom. The authors suggest that it is time to reclassify IMLNs as a separate focus of cancer and treat it as a separate entity. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer.

PubMed

Costa, C; Soares, R; Reis-Filho, J S; Leitão, D; Amendoeira, I; Schmitt, F C

2002-06-01

Cyclo-oxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis. COX-2 is induced by a wide variety of stimuli, and present during inflammation. COX-2 overexpression has been observed in colon, head and neck, lung, prostate, stomach, and breast cancer. In colon and gastric cancer, COX-2 expression was associated with angiogenesis. The aim of this study was to determine the relation between COX-2 expression and angiogenesis in breast cancer, and to correlate the expression of this enzyme with classic clinicopathological parameters. COX-2 expression was investigated by immunohistochemistry and western blotting analysis. The expression of COX-2 was then related to age, histological grade, nodal status, oestrogen receptor status, p53 expression,c-erb-B2 overexpression, mitotic counts, MIB-1 labelling index, apoptotic index, sialyl-Tn expression, transforming growth factor alpha expression, microvessel density, and disease free survival in 46 patients with invasive ductal breast carcinoma. By means of immunohistochemistry, COX-2 expression was detected in eight of the 46 carcinomas studied. Western blotting showed COX-2 protein expression in the same breast tumours, but not in normal adjacent tissues. The density of microvessels immunostained with anti-F-VIII related antigen was significantly higher in patients with COX-2 expression than in those without expression (p = 0.03). In addition, COX-2 was significantly associated with the presence of sialyl-Tn expression (p = 0.02), lymph node metastasis (p = 0.03), a high apoptotic index (p = 0.03), and a short disease free survival (p = 0.03) in univariate analyses. These data suggest that COX-2 expression is associated with angiogenesis, lymph node metastasis, and apoptosis in human breast cancer. Moreover, these results warrant further studies with larger series of patients to confirm the association with short disease free survival in patients with breast cancer.

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.

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.

Vascular Alterations in Axillary and Brachial Vessels in Patients with Axillary Web Syndrome After Breast Cancer Surgery.

PubMed

Furlan, Cintia; Matheus, Carolina Nascimben; Jales, Rodrigo Menezes; Derchain, Sophie; Sarian, Luís Otávio

2018-06-01

Surgical manipulations of the axilla may cause a condition known as Axillary Web Syndrome (AWS). The systems compromised and the sequence of events leading to this syndrome remains unknown. This study evaluated clinical, surgical, and vascular factors associated with onset and duration of AWS after breast cancer surgery. In this prospective study, 155 women were included. They were submitted to a physical examination that consisted of ultrasound Doppler of axillary and brachial vessels and the evaluation of AWS in 1, 3, and 6 months after breast cancer surgery. Women with advanced disease had a significantly higher incidence of AWS than those with early stage breast cancer (p = 0.02). In addition, women who underwent mastectomy or axillary lymph node dissection (ALND) had a significantly higher incidence of AWS in the 1-month (p < 0.01; p < 0.01) and 3-months (p < 0.01; p = 0.02) assessment rounds, respectively. The cross-sectional area of brachial artery was significantly smaller (p = 0.04) in women with AWS at the 3-months postoperative visit. The peak systolic velocity and the blood flow of the axillary artery was significantly higher in women with AWS 6 months after surgery (p < 0.03 and p = 0.02 respectively). Our study confirm the combined changes of lymphatic and vascular systems in woman with AWS, since AWS was associated with more extensive dissection of axillary lymph nodes, compromised lymph nodes, and with abnormalities of the vascular parameters.

Computational lymphatic node models in pediatric and adult hybrid phantoms for radiation dosimetry

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lamart, Stephanie; Moroz, Brian E.

2013-03-01

We developed models of lymphatic nodes for six pediatric and two adult hybrid computational phantoms to calculate the lymphatic node dose estimates from external and internal radiation exposures. We derived the number of lymphatic nodes from the recommendations in International Commission on Radiological Protection (ICRP) Publications 23 and 89 at 16 cluster locations for the lymphatic nodes: extrathoracic, cervical, thoracic (upper and lower), breast (left and right), mesentery (left and right), axillary (left and right), cubital (left and right), inguinal (left and right) and popliteal (left and right), for different ages (newborn, 1-, 5-, 10-, 15-year-old and adult). We modeled each lymphatic node within the voxel format of the hybrid phantoms by assuming that all nodes have identical size derived from published data except narrow cluster sites. The lymph nodes were generated by the following algorithm: (1) selection of the lymph node site among the 16 cluster sites; (2) random sampling of the location of the lymph node within a spherical space centered at the chosen cluster site; (3) creation of the sphere or ovoid of tissue representing the node based on lymphatic node characteristics defined in ICRP Publications 23 and 89. We created lymph nodes until the pre-defined number of lymphatic nodes at the selected cluster site was reached. This algorithm was applied to pediatric (newborn, 1-, 5-and 10-year-old male, and 15-year-old males) and adult male and female ICRP-compliant hybrid phantoms after voxelization. To assess the performance of our models for internal dosimetry, we calculated dose conversion coefficients, called S values, for selected organs and tissues with Iodine-131 distributed in six lymphatic node cluster sites using MCNPX2.6, a well validated Monte Carlo radiation transport code. Our analysis of the calculations indicates that the S values were significantly affected by the location of the lymph node clusters and that the values increased for smaller phantoms due to the shorter inter-organ distances compared to the bigger phantoms. By testing sensitivity of S values to random sampling and voxel resolution, we confirmed that the lymph node model is reasonably stable and consistent for different random samplings and voxel resolutions.

Sparse feature selection for classification and prediction of metastasis in endometrial cancer.

PubMed

Ahsen, Mehmet Eren; Boren, Todd P; Singh, Nitin K; Misganaw, Burook; Mutch, David G; Moore, Kathleen N; Backes, Floor J; McCourt, Carolyn K; Lea, Jayanthi S; Miller, David S; White, Michael A; Vidyasagar, Mathukumalli

2017-03-27

Metastasis via pelvic and/or para-aortic lymph nodes is a major risk factor for endometrial cancer. Lymph-node resection ameliorates risk but is associated with significant co-morbidities. Incidence in patients with stage I disease is 4-22% but no mechanism exists to accurately predict it. Therefore, national guidelines for primary staging surgery include pelvic and para-aortic lymph node dissection for all patients whose tumor exceeds 2cm in diameter. We sought to identify a robust molecular signature that can accurately classify risk of lymph node metastasis in endometrial cancer patients. 86 tumors matched for age and race, and evenly distributed between lymph node-positive and lymph node-negative cases, were selected as a training cohort. Genomic micro-RNA expression was profiled for each sample to serve as the predictive feature matrix. An independent set of 28 tumor samples was collected and similarly characterized to serve as a test cohort. A feature selection algorithm was designed for applications where the number of samples is far smaller than the number of measured features per sample. A predictive miRNA expression signature was developed using this algorithm, which was then used to predict the metastatic status of the independent test cohort. A weighted classifier, using 18 micro-RNAs, achieved 100% accuracy on the training cohort. When applied to the testing cohort, the classifier correctly predicted 90% of node-positive cases, and 80% of node-negative cases (FDR = 6.25%). Results indicate that the evaluation of the quantitative sparse-feature classifier proposed here in clinical trials may lead to significant improvement in the prediction of lymphatic metastases in endometrial cancer patients.

The potential of liquid-based cytology in lymph node cytological evaluation: the role of morphology and the aid of ancillary techniques.

PubMed

Rossi, E D; Martini, M; Straccia, P; Bizzarro, T; Fadda, G; Larocca, L M

2016-02-01

Our aim was to evaluate the feasibility and diagnostic accuracy of liquid-based cytology (LBC) on lymph node fine needle aspiration (FNA). FNA may fulfil a challenging role in the evaluation of the majority of primary (benign and malignant) diagnoses as well as metastatic lymph node lesions. Although the morphological features may be quite easily recognized, cytological samples with a scant cellular component may raise some issues. We appraised 263 cytological lymph nodes from different body regions analysed between January and December 2013, including 137 male and 126 female patients, and processed with LBC. The cytological diagnoses included 160 benign and 103 malignant lesions. We reported 35 benign and 73 malignant lesions from 108 with surgical follow-up. The latter malignant series included 68 metastatic lesions, four suspicious for malignancy and one inadequate sample. The cytological diagnoses were supported by 62 conclusive immunocytochemical and 28 molecular analyses. Of the 108 cases, we documented 35 true negatives, 72 true positives, one false negative and no false positives, resulting in 98.6% sensitivity, 100% specificity, 99% diagnostic accuracy, 97.2% negative predictive value and 100% positive predictive value. FNA represents the first diagnostic tool in lymph node management and a reliable approach in order to avoid an excision biopsy. Furthermore, LBC is a feasible method for ancillary tests for which methanol-fixed samples are suitable, such as immunocytochemistry and molecular analysis. © 2014 John Wiley & Sons Ltd.

Splenic hilar lymph node metastasis independently predicts poor survival for patients with gastric cancers in the upper and/or the middle third of the stomach.

PubMed

Zhu, Guo-Lian; Sun, Zhe; Wang, Zhen-Ning; Xu, Ying-Ying; Huang, Bao-Jun; Xu, Yan; Zhu, Zhi; Xu, Hui-Mian

2012-06-15

Effectiveness of splenectomy for advanced gastric cancers occupying the upper and/or the middle third of the stomach is still in debate. The aim of the present study is to elucidate the impact of splenectomy on patient survival by investigating the pathological characteristics and prognostic significance of splenic hilar lymph node metastasis. Clinicopathologic and prognostic data of 265 patients with gastric cancer in the upper and/or the middle third of the stomach who underwent the operation of en bloc resection of primary cancer and D2/D3 lymphadenectomy combined with splenectomy were retrospectively reviewed. Multivariate analysis revealed pT category, pN category, and distant lymph node metastasis independently correlated with the presence of splenic hilar lymph node metastasis. Prognoses of patients with positive splenic hilar lymph nodes were significantly poorer than that of patients with negative splenic hilar lymph nodes for the entire study population and for those who underwent R0 resection, but not for those who underwent R1-2 resection. There was no significant difference in survival between patients who underwent R0 resection with positive splenic hilar lymph nodes and those who underwent R1-2 resection. Splenic hilar lymph node metastasis was one of independent indicators predicting worse prognosis and the presence of distant metastasis after surgery. Subset analysis according to the TNM stage revealed there were significant differences in survival between patients with and without splenic hilar lymph node metastasis. Splenic hilar lymph node metastasis should be considered as one of incurable factors. Consequently, the efficiency of splenectomy aiming at prolonging survival for patients with high risk of splenic hilar lymph nodes metastasis should be questioned, although resection of invasive organs form gastric cancers has been recommended if R0 surgery could be achieved. Copyright © 2011 Wiley Periodicals, Inc.

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.

The efficacy of sentinel lymph node mapping with indocyanine green in cervical cancer.

PubMed

Kim, Ju-Hyun; Kim, Dae-Yeon; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

2018-03-09

Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients. Given the importance of lymph node metastasis, it is imperative that patients harboring metastasis are identified and can undergo appropriate treatment. Sentinel lymph node (SLN) mapping has drawn attention as a lymph node mapping technique. We evaluated the feasibility and efficacy of (SLN) mapping using indocyanine green (ICG) in cervical cancer. We performed a single-center, retrospective study of 103 surgically treated cervical cancer patients who underwent SLN mapping. After using ICG to detect SLN during surgery, we removed the SLNs followed by laparoscopic or robotic-assisted radical surgery and bilateral pelvic lymphadenectomy. Stage IB1 was the most common (61.17%). At least one SLN was detected in all cases. Eighty-eight patients (85.44%) had bilateral pelvic SLNs. The mean number of SLN per patient was 2.34. The side-specific sensitivity was 71.43%, the specificity was 100%, the negative predictive value (NPV) was 93.98%, and the false negative rate (FNR) was 28.57%. In cases of tumors smaller than 2 cm with negative lymph node metastasis on imaging, the study revealed a side-specific sensitivity of 100%, a specificity of 100%, a NPV of 100%, and a FNR of 0%. Large tumor size (≥ 4 cm), a previous history of a loop electrosurgical excision procedure (LEEP), depth of invasion (≥ 50%), the microscopic parametrial (PM) invasion, and vaginal extension were significantly associated with the false-negative detection of SLN. Moreover, the microscopic PM invasion was the only risk factor of the false-negative detection of SLN in multivariate analysis. SLN mapping with ICG in cervical cancer is feasible and has high detection rate. The sensitivity of 100% was high enough to perform SLN biopsy alone in an early stage in which the tumor is less than 2 cm, with no lymphadenopathy on image examination. However, for large or invasive tumors, we would have to be cautious about performing SLN biopsy alone. Retrospectively registered 2017-0600.

[Numbers of lymph nodes in large intestinal resections for colorectal carcinoma].

PubMed

Motycka, V; Ferko, A; Tycová, V; Nikolov, Hadzi; Sotona, O; Cecka, F; Dusek, T; Chobola, M; Pospísil, I

2010-03-01

Precise evaluation of lymph nodes in the surgical specimen is crucial for the staging and subsequent decision about the adjuvant therapy in colorectal cancer. Prognosis of the patients can be assessed only in cases when at least 12 lymph nodes in the surgical specimen are examined. To evaluate the radicalism of resections for colorectal carcinoma after introducing laparoscopic approach. We compared all resections for primary colorectal cancer and rectal cancer (C 18-C20) performed in the Department of Surgery in University Hospital Hradec Králové in the years 2005 and 2008 and we evaluated numbers of examined lymph nodes in the surgical specimens. The patients with recurrent tumours and the patients with complete pathological response (negative histology) after neoadjuvant therapy were excluded from the study. 117 patients were included in the study in 2005, 2 of them were operated laparoscopically. 155 patients (more by 32.5%) were included in the study in 2008, 53 of them (34.2%) were operated laparoscopically. In tumours of the right part of the colon (C180-C184) treated by right hemicolectomy: on an average 7.9 (+/- 5.3) lymph nodes were examined in the specimens in 2005, and 15.3 (+/- 7.0) lymph nodes in 2008. In tumours of the left part of the colon (C185-C186) treated by left hemicolectomy: 6.5 (+/- 5.1) lymph nodes were examined in 2005, and 19.6 (+/- 15.6) in 2008. In tumours of the sigmoid colon (C187) 9.1 (+/- 6.9) lymph nodes were examined in 2005,and 15.4 (+/- 7.9) in 2008. In tumours of the rectosigmoid junction (C19) 8.0 (+/- 6.9) lymph nodes were examined in 2005, and 17.8 (+/- 11.2) in 2008. In rectal cancer (C20) 5.2 (+/- 4.5) lymph nodes were examined in 2005, and 13.6 (+/- 12.5) in 2008. There is a significant difference in a number of examined lymph nodes in patients without neodadjuvant treatment compared to those with neoadjuvant chemoradiotherapy and neoadjuvant radiotherapy. In 2005, in an average 3.7 (+/- 3.3) lymph nodes were removed in rectal resections after neoadjuvant chemoradiotherapy, in 2008 in an average 7.6 (+/- 6.1) lymph nodes were removed. In 2005, in an average 5.1 (+/- 3.7) lymph nodes in rectal resections after neoadjuvant radiotherapy were removed, in 2008 6.3 (+/- 4.3) lymph nodes were removed. In 2005, in an average 7.0 (+/- 5.5) lymph nodes in rectal resections without neoadjuvant therapy were removed, in 2008 20.9 (+/- 14.1) lymph nodes were removed. Laparoscopic resections were comparable with open resections regarding the number of examined lymph nodes in our group of patients. Introducing the laparoscopic approach to resections of colorectal carcinomas did not decrease radicalism of the operation as to the number of removed lymph nodes.

Lymphatics and the breast

MedlinePlus Videos and Cool Tools

... lymphatic system called lymph nodes are distributed at specific locations throughout the body. There is also an ... result in the formation of a secondary cancer mass in a different location of the body. Regular ...

Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission

ClinicalTrials.gov

2017-12-07

HER2/Neu Negative; No Evidence of Disease; One or More Positive Axillary Nodes; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Starry sky sign: A prevalent sonographic finding in mediastinal tuberculous lymph nodes.

PubMed

Alici, Ibrahim Onur; Demirci, Nilg N Yilmaz; Yilmaz, Aydin; Karakaya, Jale; Erdogan, Yurdanur

2015-01-01

We report a prevalent finding in tuberculous lymphadenitis (TL): Starry sky sign, hyperechoic foci without acoustic shadows over a hypoechoic background. We retrospectively searched the database for a possible relationship of starry sky sign with a specific diagnosis and also the prevalence and accuracy of the finding. Starry sky sign was found in 16 of 31 tuberculous lymph nodes, while none of other lymph nodes (1,015 lymph nodes) exhibited this finding; giving a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 51.6%, 100%, 100%, 98.5%, and 98.5%, respectively. Bacteriologic and histologic findings are gold standard in the diagnosis of tuberculosis, but this finding may guide the bronchoscopist in choosing the more pathologic node within a station and increase the diagnostic yield as it may relate to actively dividing mycobacteria.

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

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.

Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

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

Goldsmith, Benjamin; Baumann, Brian C.; He, Jiwei

2014-03-01

Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, andmore » external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended coverage of pelvic lymph nodes up to the level of the common iliac nodes may be warranted in subsets of patients.« less

Discrimination of benign and malignant lymph nodes at 7.0T compared to 1.5T magnetic resonance imaging using ultrasmall particles of iron oxide: a feasibility preclinical study.

PubMed

Kinner, Sonja; Maderwald, Stefan; Albert, Juliane; Parohl, Nina; Corot, Claire; Robert, Philippe; Baba, Hideo A; Barkhausen, Jörg

2013-12-01

To investigate the feasibility and performance of 7T magnetic resonance imaging compared to 1.5T imaging to discriminate benign (normal and inflammatory changed) from tumor-bearing lymph nodes in rabbits using ultrasmall particles of iron oxide (USPIO)-based contrast agents. Six New Zealand White rabbits were inoculated with either complete Freund's adjuvant cell suspension (n = 3) to induce reactively enlarged lymph nodes or with VX2 tumor cells to produce metastatic lymph nodes (n = 3). Image acquisition was performed before and 24 hours after bolus injection of an USPIO contrast agent at 1.5T and afterward at 7T using T1-weighted and T2*-weighted sequences. Sensitivities, specificities, and negative and positive predictive values for the detection of lymph node metastases were calculated for both field strengths with histopathology serving as reference standard. Sizes of lymph nodes with no, inflammatory, and malignant changes were compared using a Mann-Whitney U-test. All 24 lymph nodes were detected at 1.5T as well as at 7T. At 1.5T, sensitivity amounted to 0.67, while specificity reached a value of 1. At the higher field strength (7T), imaging was able to reach sensitivity and specificity values of 1. No statistical differences were detected concerning lymph node sizes. Magnetic resonance lymphography with USPIO contrast agents allows for differentiation of normal and reactively enlarged lymph nodes compared to metastatic nodes. First experiments at 7T show promising results compared to 1.5T, which have to be evaluated in further trials. Copyright © 2013. Published by Elsevier Inc.

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.

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.