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Sample records for invasive ductal carcinomas

  1. Invasive Ductal Carcinoma Developing From Fibroadenoma

    PubMed Central

    Aydın, Oğuz Uğur; Soylu, Lütfi; Ercan, Aydan İlkme; Bilezikçi, Banu; Koçak, Savaş

    2015-01-01

    Fibroadenomas are the most common benign breast lesions in adolescent and young women. It is most frequently observed in the 3rd decade. Although it is considered benign, evidence of malignant transformation is available. Cancer development may be from ground of fibroadenoma or near breast tissue. A case of a fibroadenoma coexisting with an invasive ductal carcinoma of the breast in a 31-year-old female is presented. The patient presented with the chief complaint of having a palpable mass in her right breast for the last 10 years. Mammography revealed a mass with microcalcifications. Core biopsy was performed, and the results indicated an invasive carcinoma. Breast-conserving surgery with sentinel lymph node biopsy was performed. The pathological features revealed a fibroadenoma coexisting with an invasive ductal carcinoma. This case suggests that clinicians and radiologists should always pay attention to the associated malignant imaging characteristics whenever a mass was followed up as fibroadenoma.

  2. Monitoring the progression from intraductal carcinoma to invasive ductal carcinoma based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-09-01

    Intraductal carcinoma is a precancerous lesion of the breast and the immediate precursor of invasive ductal carcinoma. Multiphoton microscopy (MPM) was used to monitor the progression from intraductal carcinoma to invasive ductal carcinoma, which can improve early detection of precursor lesions and halt progression to invasive neoplastic disease. It was found that MPM has the capability to reveal the qualitative changes in features of cells, structure of basement membranes, and architecture of collagens during the development from intraductal carcinoma to invasive ductal carcinoma, as well as the quantitative alterations in nuclear area, circle length of basement membrane, and collagen density. Combined with intra-fiberoptic ductoscopy or transdermal biopsy needle, MPM has the potential to provide immediate histological diagnosis of tumor progression in the field of breast carcinoma.

  3. Mucinous subtype of invasive ductal carcinoma arising within a fibroadenoma.

    PubMed

    Monsefi, Nahid; Nikpour, Hossein; Safavi, Moienadin; Lashkarizadeh, Mohammad Reza; Dabiri, Shahriar

    2013-06-01

    Fibroadenoma is a common benign tumor observed during the second and third decades of life. Malignancy transformation in the epithelial component of a fibroadenoma is rare and can occur 20 years after its diagnosis. Mammographic findings in this phenomenon include indistinct margins and microcalcifications. Here we present a 58-year-old woman with a mobile, lateral upper quadrant mass that was rather firm when palpated. The mammography showed a lobulated mass without calcification suggestive of a benign process, most probably fibroadenoma. However the excisional biopsy contained both an intracanalicular fibroadenoma and invasive ductal carcinoma with mucinous components.

  4. Comparison of the clinicopathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast.

    PubMed

    Zengel, Baha; Yararbas, Ulkem; Duran, Ali; Uslu, Adam; Elıyatkın, Nukhet; Demırkıran, Mehmet Ali; Cengiz, Fevzi; Şimşek, Cenk; Postacı, Hakan; Vardar, Enver; Durusoy, Raika

    2015-07-01

    In this retrospective analysis, the clinicopathological features and pattern of metastatic spread of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed ductal/lobular carcinoma (MDLC), together with the type and outcome of surgical intervention, were comparatively evaluated. A total of 633 breast cancer patients with histopathological subtype IDC, ILC or MDLC were included in the study. The mean age was 52.6 ± 12.7 years. Follow-up period ranged between 0 and 33 (median 6.0) years. The groups were compared with respect to age, tumor size, nodal involvement, stage, hormonal therapy, multicentricity, multifocality, bilaterality, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, p53, and Ki67 expression, disease-free survival (DFS) and overall survival (OS) rates, and surgical approach. The distribution of patients was as follows: IDC 508 (80.3 %), ILC 78 (12.3 %), MDLC 47 (7.4 %). Among the parameters evaluated, statistically significant differences were observed in mean tumor size (IDC 2.5 ± 1.98 cm, ILC 3.0 ± 1.8 cm, MDLC 3.2 ± 2.4 cm), advanced T stage (T3 + T4) at diagnosis (IDC 14.7 %, ILC 21.4 %, MDLC 25.6 %), N stage (N0 was dominant in IDC and ILC; N3 was dominant in MDLC), tumor-node-metastasis (TNM) stage (stage II was dominant in IDC and ILC; stage III was dominant in MDLC), HER2/neu expression (IDC 23.8 %, ILC 11.8 %, MDLC 21.4 %), and frequency of bone metastasis (IDC 14.3 %, ILC 17.9 %, MDLC 25.5 %). MDLC-type tumors have different histopathological characteristics and are often diagnosed at advanced stage. However, their survival outcomes do not vary significantly from ILC and IDC.

  5. Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma

    PubMed Central

    Murakami, Eriko; Nakanishi, Yoko; Hirotani, Yukari; Ohni, Sumie; Tang, Xiaoyan; Masuda, Shinobu; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao; Yamada, Tsutomu; Nemoto, Norimichi

    2016-01-01

    Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC. PMID:27917007

  6. Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

    PubMed Central

    Aguiar, Fernando N.; Mendes, Henrique N.; Cirqueira, Cinthya S.; Bacchi, Carlos E.; Carvalho, Filomena M.

    2013-01-01

    OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. PMID:23778411

  7. [Triexponential diffusion analysis in invasive ductal carcinoma and fibroadenoma].

    PubMed

    Nakagawa, Masayuki; Miyati, Tosiaki; Hayashi, Tatsuya; Kanao, Syotaro; Taniguchi, Masahiro; Higashimura, Kyoji; Toi, Masakazu; Togashi, Kaori

    2014-03-01

    To simultaneously obtain information on diffusion and perfusion in breast lesions by diffusion-weighted magnetic resonance imaging (DWI), we analyzed three diffusion components using a triexponential function. Eighteen subjects [10 with invasive ductal carcinoma (IDC), 8 with fibroadenoma] were evaluated using DWI with multiple b-values. We derived perfusion-related diffusion, fast free diffusion, and slow restricted diffusion coefficients (Dp, Df, Ds) calculated from the triexponential function using the DWI data. Moreover, the triexponential analysis was compared with biexponential and monoexponential analyses. Each diffusion coefficient with a triexponential function was correlated to a relative enhancement ratio (RER) using dynamic contrast-enhanced MRI. In triexponential analysis, Dp and Ds in IDC were significantly higher than those for fibroadenoma. There was no correlation between each diffusion coefficient from the triexponential analysis in any of the groups (Dp, Df, and Ds), but biexponential analysis revealed a positive correlation between each diffusion coefficient in breast lesions. Strong correlations were found between Dp and RERs. Triexponential analysis thus makes it possible to obtain, in noninvasive fashion, more detailed diffusion and perfusion information in breast lesions.

  8. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma

    PubMed Central

    Cha, Yoon Jin; Kim, Hye Min; Koo, Ja Seung

    2017-01-01

    We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p < 0.001) differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001) and perilipin A in luminal A-type IDC (p = 0.007). Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004) and acyl-CoA oxidase 1 positivity (p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression. PMID:28124996

  9. Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.

    PubMed

    Kim, Shinn Young; Jung, Seung-Hyun; Kim, Min Sung; Baek, In-Pyo; Lee, Sung Hak; Kim, Tae-Min; Chung, Yeun-Jun; Lee, Sug Hyung

    2015-04-10

    Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.

  10. Differences and Relationships Between Normal and Atypical Ductal Hyperplasia, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma Tissues in the Breast Based on Raman Spectroscopy.

    PubMed

    Han, Bing; Du, Ye; Fu, Ton; Fan, Zhimin; Xu, Shuping; Hu, Chengxu; Bi, Lirong; Gao, Ting; Zhang, Haipeng; Xu, Weiqing

    2017-02-01

    The aim of this study was to find the differences and relationships between normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) lesions of the breast based on biochemical characteristics determined by Raman spectroscopy (RS). After collecting 39 frozen sections from patients who underwent surgical resection or mammotome biopsy, nine normal tissues, seven ADH, eight DCIS, and 15 IDC lesions were detected using confocal RS. We then used leave-one-out cross-validation (LOOCV) and radial basis function (RBF) to build a support vector machine (SVM) diagnosis model. Pronounced mean Raman spectra differences were observed between normal tissues, ADH, DCIS, and IDC tissues. Most noticeable was the increased protein and reduced lipid levels of ADH tissues compared to normal tissues. The major spectra differences in ADH, DCIS, and IDC spectrograms were evidenced by a red shift with a broad peak of CH2 (1301 cm(-1)), the intensity of the stretching vibration peak of carotenoids (1526 cm(-1)), a relatively strong band of amide-I (1656 cm(-1)), and the nuclear (882 cm(-1)) acid peak. Atypical ductal hyperplasia tissues had the largest constituent variations between subjects. During the disease progression, IDC tissues have smaller inter-subject constituent variations than DCIS and ADH tissues. The overall accuracy of SVM model is 74.39%. The sensitivities of normal tissue, ADH, DCIS, and IDC are 62.5%, 50%, 90%, and 66.7%, respectively. The specificities of normal tissue, ADH, DCIS, and IDC are 100%, 100%, 66.7%, and 89.06%, respectively. Atypical ductal hyperplasia shows significant differences and the relationship between normal tissue and malignant disease. Further study to explain the biochemical relationships between these differences will shed more light into a better understanding of the mechanism by which ADH converts to DCIS and to IDC.

  11. Inhibition of the Transition of Ductal Carcinoma In Situ to Invasive Ductal Carcinoma by a Gemini Vitamin D Analog

    PubMed Central

    Wahler, Joseph; So, Jae Young; Kim, Yeoun Chan; Liu, Fang; Maehr, Hubert; Uskokovic, Milan; Suh, Nanjoo

    2014-01-01

    Ductal carcinoma in situ (DCIS) is a non-malignant lesion of the breast with the potential to progress to invasive ductal carcinoma (IDC). The disappearance and breakdown of the myoepithelial cell layer and basement membrane in DCIS have been identified as major events in the development of breast cancer. The MCF10DCIS.com cell line is a well-established model which recapitulates the progression of breast cancer from DCIS to IDC. We have previously reported that a novel Gemini vitamin D analog, 1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-cholecalciferol (BXL0124) is a potent inhibitor of the growth of MCF10DCIS.com xenografted tumors without hypercalcemic toxicity. In the present study, we utilized the MCF10DCIS.com in vivo model to assess the effects of BXL0124 on breast cancer progression from weeks 1 to 4. Upon DCIS progression to IDC from weeks 3 to 4, tumors lost the myoepithelial cell layer and basement membrane as shown by immunofluorescence staining with smooth muscle actin (SMA) and laminin 5, respectively. Administration of BXL0124 maintained the critical myoepithelial cell layer as well as basement membrane, and animals treated with BXL0124 showed a 43% reduction in tumor volume by week 4. BXL0124 treatment decreased cell proliferation and maintained vitamin D receptor (VDR) levels in tumors. In addition, the BXL0124 treatment reduced the mRNA levels of matrix metalloproteinases (MMPs) starting at week 3, contributing to the inhibition of invasive transition. Our results suggest that the maintenance of DCIS plays a significant role in the cancer preventive action of the Gemini vitamin D BXL0124 during the progression of breast lesions. PMID:24691501

  12. Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report.

    PubMed

    Neto, Guerino Barbalaco; Rossetti, Claudia; Souza, Natalia A; LA Fonseca, Fernando; Azzalis, Ligia Ajaime; Junqueira, Virginia Berlanga Campos; Valenti, Vitor E; de Abreu, Luiz Carlos

    2012-04-25

    This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.

  13. Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

    PubMed Central

    2012-01-01

    This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional. PMID:22534285

  14. Left adrenal gland metastasis of breast invasive ductal carcinoma: A case report.

    PubMed

    He, Tao; Liu, Jiaju; Li, Yifan; Jin, L U; Sun, Shuolei; Ni, Liangchao; Mao, Xiangming; Yang, Shangqi; Lai, Yongqing

    2016-05-01

    The majority of the metastatic lesions of the adrenal gland normally originate from lung cancer, colon malignant tumor, renal cell carcinoma and melanoma. However, adrenal gland metastasis that metastasize from breast invasive ductal carcinoma are extremely rare. The present study reported a rare case of left adrenal gland metastasis in a 35-year-old female who was diagnosed as breast carcinoma 5 years ago with a mass located on the left adrenal gland, which was detected during a routine examination. The patient was asymptomatic and adrenal gland computed tomography revealed a mass in the left adrenal gland. Definitive preoperative diagnosis failed to be established. Left adrenal gland laparoscopic adrenalectomy was performed and the diagnosis of adrenal gland metastasis of breast invasive ductal carcinoma was confirmed by pathological and immunohistochemical examination. The patient remained in good condition by the time of writing.

  15. Rare coexistence of invasive papillary carcinoma with infiltrating ductal carcinoma in male breast: report of a case.

    PubMed

    Bhatia, Alka; Uma Nahar Saikia; Kumar, Yashwant

    2008-07-01

    Invasive papillary breast carcinoma is a subtype of breast cancer that is more frequent in males. An intraductal carcinoma can coexist with it but association of an infiltrating carcinoma has not been described. This report presents a rare case of a 35-year-old man with dual malignancy in the same breast. The patient had two separate nodules, one with the morphology of invasive papillary carcinoma and the other having features of an infiltrating ductal carcinoma. To the best of our knowledge this is the first case report describing the coexistence of these two entities.

  16. Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.

    PubMed

    Lacroix-Triki, Magali; Suarez, Paula H; MacKay, Alan; Lambros, Maryou B; Natrajan, Rachael; Savage, Kay; Geyer, Felipe C; Weigelt, Britta; Ashworth, Alan; Reis-Filho, Jorge S

    2010-11-01

    Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the

  17. Invasive Ductal Breast Carcinoma Underneath a Lipoma in a Male Patient

    PubMed Central

    Landero, James; Glick, Bradley P.

    2012-01-01

    Male breast cancer is a rare malignancy and accounts for less than one percent of all cancers in men. The authors describe the case of a 76-year-old Caucasian man with invasive ductal breast carcinoma who presented with a common lipoma. This paper reviews the current literature on epidemiology, risk factors, etiology, different types of breast cancer, clinical presentation, imaging, diagnostic workup, and treatment. PMID:23125888

  18. Myiasis associated with an invasive ductal carcinoma of the left breast: case study

    PubMed Central

    Rodrigues, Felipe Tavares; Klemig, Larissa Raquel; Cardozo, Marcos Roberto Pereira; Alves, Paulo Cesar; Aguiar, Valéria Magalhães; Lessa, Claudia Soares

    2017-01-01

    ABSTRACT Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis. PMID:28591263

  19. Comparison of invasive micropapillary and triple negative invasive ductal carcinoma of the breast.

    PubMed

    Chen, Hong-liang; Ding, Ang

    2015-12-01

    Invasive micropapillary carcinoma (IMPC) of the breast and triple negative breast cancer (TNBC) are both aggressive subtypes, but little information is available on their comparison. Retrospective analysis of 95 IMPC and 200 TNBC-IDC (invasive ductal carcinoma) was conducted to compare the clinicopathologic characteristics and survivals. For IMPC, pN was the independent prognostic factor of local-regional recurrence free survival (LRRFS) (P = 0.045) and metastasis free survival (MFS) (P = 0.048), but not of overall survival (OS) (P = 0.165). For TNBC, pT and lymphovascular invasion (LVI) were both independent prognostic factors of MFS (pT: P = 0.006, LVI: P = 0.010) and OS (pT: P = 0.006, LVI: P = 0.001), but not for LRRFS (pT: P = 0.060, LVI: P = 0.503). IMPC exhibited more aggressive features than TNBC, including larger tumor size, a greater proportion of nodal involvement, and an increased incidence of LVI. After a median follow-up duration of 61 months, 5y-LRRFS rate was lower in IMPC than in TNBC, in entire cohort (71.4 ± 4.8% vs. 89.8 ± 2.2%, P < 0.001) and in node positive cases (64.2 ± 5.9% vs. 81.7 ± 4.4%, P = 0.048). A tendency of lower 5y-MFS rate was observed in TNBC compared with in IMPC, in node positive cases (63.8 ± 5.5% vs. 74.8 ± 5.5%, P = 0.053) and in node negative cases (80.1 ± 3.6% vs. 96.2 ± 3.8%, P = 0.052), but it did not reach significance. 5y-OS was similar between IMPC and TNBC (81.9 ± 4.7% vs. 79.8 ± 3.1%, P = 0.475). IMPC is featured with high rate of lymph node involvement which is strongly associated with high rate of LRR. TNBC is featured with high rate of early distant metastasis without increase of nodal metastases. The survival is still relatively poor even in node negative cases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Expression of DNA methylation-related proteins in invasive lobular carcinoma of breast: comparison to invasive ductal carcinoma.

    PubMed

    Cha, Yoon Jin; Kim, Hye Min; Koo, Ja Seung

    2017-11-01

    We aimed to compare the expression of DNA methylation-related proteins in invasive lobular carcinoma (ILC) of breast with those of invasive ductal carcinoma (IDC) of breast and to assess its potential clinical application. Immunohistochemical staining of DNS methylation-related proteins (5-meC, DNMT1, DNMT3B and ISL-1) was applied to tissue microarrays generated from 108 ILCs and 203 IDCs. Protein expression and its correlation with clinicopatholgic variables were statistically analyzed. ISL-1 and DNMT3B were highly expressed in ILC (p<0.001) and tumoral 5-meC was highly expressed in IDC (p=0.006). DNMT1 (p<0.001) showed higher expression rate in luminal A type ILC. ISL-1 and DNMT3B showed higher expression rate in both luminal A type and luminal B type of ILC (p<0.05). In IDC, tumoral 5-meC commonly showed high positive (p=0.039). On univariate analysis, shorter disease free survival of ILC was associated with DNMT1 high positivity (p=0.001) and ISL-1 positivity (p=0.018). DNA methylation-related proteins are differentially expressed in ILC and IDC, and DNMT1, DNMT3B and ISL-1 show high expression rate in ILC.

  1. Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

    PubMed

    Dobbs, Jessica L; Shin, Dongsuk; Krishnamurthy, Savitri; Kuerer, Henry; Yang, Wei; Richards-Kortum, Rebecca

    2016-09-01

    Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions. © 2016 UICC.

  2. Morphologic, molecular and microenvironment factors associated with stromal invasion in breast ductal carcinoma in situ: Role of myoepithelial cells.

    PubMed

    Aguiar, Fernando N; Cirqueira, Cinthya S; Bacchi, Carlos E; Carvalho, Filomena M

    2015-01-01

    Ductal carcinoma in situ is the last step preceding invasive ductal carcinoma in breast carcinogenesis. We investigated the role of myoepithelial cells and epithelium characteristics as predictors of the risk of stromal invasion. We selected 236 cases with initial diagnosis of DCIS followed by surgical ressection distributed in groups 1 (without invasion) and 2 (with invasive carcinoma). The risk of stromal invasion after a DCIS diagnosis in biopsy was associated to triple-negative profile and loss of CD10 expression by myoepithelial cells, and inversely associated with CK5/6 expression by neoplastic cells and high expression of Smooth Muscle Myosin Heavy Chain (SMMHC) by myoepithelial cells. A combination of characteristics of epithelial and myoepithelial cells in DCIS in biopsy specimens is related to the risk of stromal invasion.

  3. Squamoid eccrine ductal carcinoma.

    PubMed

    Saraiva, Maria Isabel Ramos; Vieira, Marcella Amaral Horta Barbosa; Portocarrero, Larissa Karine Leite; Fraga, Rafael Cavanellas; Kakizaki, Priscila; Valente, Neusa Yuriko Sakai

    2016-01-01

    Squamoid eccrine ductal carcinoma is an eccrine carcinoma subtype, and only twelve cases have been reported until now. It is a rare tumor and its histopathological diagnosis is difficult. Almost half of patients are misdiagnosed as squamous cell carcinoma by the incisional biopsy. We report the thirteenth case of squamoid eccrine ductal carcinoma. Female patient, 72 years old, in the last 6 months presenting erythematous, keratotic and ulcerated papules on the nose. The incisional biopsy diagnosed squamoid eccrine ductal carcinoma. After excision, histopathology revealed positive margins. A wideningmargins surgery and grafting were performed, which again resulted in positive margins. The patient was then referred for radiotherapy. After 25 sessions, the injury reappeared. After another surgery, although the intraoperative biopsy showed free surgical margins, the product of resection revealed persistent lesion. Distinction between squamoid eccrine ductal carcinoma and squamous cell carcinoma is important because of the more aggressive nature of the first, which requires wider margins surgery to avoid recurrence.

  4. Squamoid eccrine ductal carcinoma*

    PubMed Central

    Saraiva, Maria Isabel Ramos; Vieira, Marcella Amaral Horta Barbosa; Portocarrero, Larissa Karine Leite; Fraga, Rafael Cavanellas; Kakizaki, Priscila; Valente, Neusa Yuriko Sakai

    2016-01-01

    Squamoid eccrine ductal carcinoma is an eccrine carcinoma subtype, and only twelve cases have been reported until now. It is a rare tumor and its histopathological diagnosis is difficult. Almost half of patients are misdiagnosed as squamous cell carcinoma by the incisional biopsy. We report the thirteenth case of squamoid eccrine ductal carcinoma. Female patient, 72 years old, in the last 6 months presenting erythematous, keratotic and ulcerated papules on the nose. The incisional biopsy diagnosed squamoid eccrine ductal carcinoma. After excision, histopathology revealed positive margins. A wideningmargins surgery and grafting were performed, which again resulted in positive margins. The patient was then referred for radiotherapy. After 25 sessions, the injury reappeared. After another surgery, although the intraoperative biopsy showed free surgical margins, the product of resection revealed persistent lesion. Distinction between squamoid eccrine ductal carcinoma and squamous cell carcinoma is important because of the more aggressive nature of the first, which requires wider margins surgery to avoid recurrence. PMID:28099603

  5. Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma.

    PubMed

    Johnson, Clint E; Gorringe, Kylie L; Thompson, Ella R; Opeskin, Ken; Boyle, Samantha E; Wang, Yuker; Hill, Prue; Mann, G Bruce; Campbell, Ian G

    2012-06-01

    Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma (IDC). Annotation of the genetic differences between the two lesions may assist in the identification of genes that promote the invasive phenotype. Synchronous DCIS and IDC cells were microdissected from FFPE tissue and analysed by molecular inversion probe (MIP) copy number arrays. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared) indicating a common clonal origin although there is evidence that the DCIS continues to evolve in parallel with the co-existing IDC. Four chromosomal regions of loss (3q, 6q, 8p and 11q) and four regions of gain (5q, 16p, 19q and 20) were recurrently affected in IDC but not in DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. IDC-specific regions include genes with previous links to breast cancer progression and potential therapeutic targets such as AXL, SPHK1 and PLAUR.

  6. Multiphoton microscopic imaging of fibrotic focus in invasive ductal carcinoma of the breast

    NASA Astrophysics Data System (ADS)

    Chen, Sijia; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    During the proliferation of breast cancer, the desmoplastic can evoke a fibrosis response by invading healthy tissue. Fibrotic focus (FF) in invasive ductal carcinoma (IDC) of the breast had been reported to be associated with significantly poorer survival rate than IDC without FF. As an important prognosis indicator, it's difficult to obtain the exact fibrotic information from traditional detection method such as mammography. Multiphoton imaging based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) has been recently employed for microscopic examination of unstained tissue. In this study, multiphoton microscopy (MPM) was used to image the fibrotic focus in invasive ductal carcinoma tissue. The morphology and distribution of collagen in fibrotic focus can be demonstrated by the SHG signal. Variation of collagen between IDC with and without FF will be examined and further characterized, which may be greatly related to the metastasis of breast cancer. Our result suggested that the MPM can be efficient in identifying and locating the fibrotic focus in IDC. Combining with the pathology analysis and other detecting methods, MPM owns potential in becoming an advanced histological tool for detecting the fibrotic focus in IDC and collecting prognosis information, which may guide the subsequent surgery option and therapy procedure for patients.

  7. Comparison of Clinicopathological Features and Treatment Results between Invasive Lobular Carcinoma and Ductal Carcinoma of the Breast.

    PubMed

    Park, Jun Su; Choi, Doo Ho; Huh, Seung Jae; Park, Won; Kim, Young Il; Nam, Seok Jin; Lee, Jeong Eon; Kil, Won Ho

    2015-09-01

    The purpose of this study was to assess the incidence of invasive lobular carcinoma (ILC) and to compare the clinicopathological features and treatment results after breast conserving surgery (BCS) followed by radiotherapy between ILC and invasive ductal carcinoma (IDC). A total of 1,071 patients who underwent BCS followed by radiotherapy were included in the study. Medical records and pathological reports were retrospectively reviewed. The incidence of ILC was 5.2% (n=56). Bilateral breast cancer, lower nuclear grade, and hormone receptor-positive breast cancer were more frequent in patients with ILC than in those with IDC. There were no cases of lymphovascular invasion or the basal-like subtype in patients with ILC. There were no statistically significant differences in patterns of failure or treatment outcomes between patients with ILC and those with IDC. The development of metachronous contralateral breast cancer was more frequent in patients with IDC (n=27). Only one patient with ILC developed contralateral breast cancer, with a case of ductal carcinoma in situ. The incidence of ILC was slightly higher in our study than in previous Korean studies, but was lower than the incidences reported in Western studies. The differences we observed in clinico pathological features between ILC and IDC were similar to those described elsewhere in the literature. Although there were no statistically significant differences, there was a trend toward better disease-specific survival and disease-free survival rates in patients with ILC than in those with IDC.

  8. Synchronous presentation of invasive ductal carcinoma and mantle cell lymphoma: a diagnostic challenge in menopausal patients.

    PubMed

    Woo, Edward J; Baugh, Aaron D; Ching, Karen

    2016-01-22

    Synchronous presentation of breast carcinoma and non-Hodgkin lymphoma (NHL) is a rare occurrence (Bradford PT, Freedman DM, Goldstein AM, Tucker MA. Increased risk of second primary cancers after a diagnosis of melanoma. Arch Dermatol 2010; 146: :265-72; Dutta Roy S, Stafford JA, Scally J, Selvachandran SN. A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma. World J Surg Oncol 2003; 1: :27; Suresh Attili VS, Dadhich HK, Rao CR, Bapsy PP, Batra U, Anupama G et al. A case of breast cancer coexisting with B-cell follicular lymphoma. Austral Asian J Cancer 2007; 6: :155-6). In particular, only two reported cases on synchronous presentation of invasive ductal carcinoma (IDC) and mantle cell lymphoma (MCL) exist in the English literature. Owing to the rarity, there is a lack of consensus about underlying mechanism as well as optimal treatment strategy, and diagnosing both malignancies together without a delay remains a complex clinical challenge. We report a case of synchronous presentation of IDC and MCL in a 67-year-old female patient whose MCL diagnosis was delayed due to a misinterpretation of her B symptoms as postmenopausal, with a review of the literature on concurrently occurring breast carcinoma and NHL.

  9. Multiple Intraglandular Metastases in a Patient with Invasive Ductal Carcinoma of the Pancreas.

    PubMed

    Morita, Shinichi; Onaya, Hiroaki; Kishi, Yoji; Hiraoka, Nobuyoshi; Arai, Yasuaki

    2015-01-01

    A 56-year-old man was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas, with three other tumors detected in the body and tail. Magnetic resonance imaging showed similar enhancement patterns and signal intensities in all four lesions. The patient underwent total pancreatectomy based on a preoperative diagnosis of multiple invasive ductal carcinomas. Histopathologically, the lesion in the pancreatic head was considered to be the primary lesion, while the others were diagnosed as metastases. This is a rare case of pancreatic cancer with intraglandular metastases. The possibility of this differential diagnosis should thus be considered when imaging shows multiple hypovascular lesions in the pancreas.

  10. [A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].

    PubMed

    Toyoda, Yasuhiro; Hojo, Shigeyuki; Yoshioka, Setsuko; Kojima, Fumiyoshi; Matsunaga, Hiroki; Fujie, Yujiro; Fukunaga, Hiroki; Ota, Hirofumi; Endo, Wakio; Maeura, Yoshiichi

    2013-11-01

    A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.

  11. High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma.

    PubMed

    Abdel-Fatah, Tarek M A; Powe, Desmond G; Hodi, Zsolt; Lee, Andrew H S; Reis-Filho, Jorge S; Ellis, Ian O

    2007-03-01

    This study was undertaken to determine the morphologic features and frequency of putative precursor lesions involved in the development of some pure forms of special types and low grade breast carcinoma. We reviewed 147 successive tumor cases, comprising tubular carcinoma (TC); pure type (n=56) and mixed type (n=20), invasive lobular carcinoma (ILC); classic type (n=57), and tubulolobular carcinoma (TLC; n=14). The presence of preinvasive lesions including columnar cell lesions (CCLs), usual epithelial hyperplasia, ductal carcinoma in situ (DCIS), and lobular neoplasia (LN) was determined. Estrogen receptor and E-cadherin immunohistochemistry was performed. Ninety-five percent (95%) of pure TCs had associated CCLs with the majority showing flat epithelial atypia. Atypical ductal hyperplasia (ADH)/DCIS was present in 89% patients. Colocalization of CCL, ADH/DCIS, and TC was seen in 85% patients, all displaying the same cytologic-nuclear morphology in most cases. LN was seen in 16%. In ILC, 91% cases showed LN. CCL and ADH/DCIS were seen in 60% and 42% cases, respectively. E-cadherin was positive in TLC but reduced in TC and completely absent in ILC. In conclusion, our findings support the hypothesis that CCLs are associated with pure and mixed forms of TC, and that LN is involved in ILC development. Our observations suggest that these lesions represent family members of low grade precursor, in situ and invasive neoplastic lesions of the breast. Molecular studies are being performed to substantiate the hypothesis that tubular and lobular carcinomas have direct evolutionary links to CCLs and flat epithelial atypia.

  12. Mass Spectrometric Characterization of Protein Structure Details Refines the Proteome Signature for Invasive Ductal Breast Carcinoma

    NASA Astrophysics Data System (ADS)

    Röwer, Claudia; Koy, Cornelia; Hecker, Michael; Reimer, Toralf; Gerber, Bernd; Thiesen, Hans-Jürgen; Glocker, Michael O.

    2011-03-01

    Early diagnosis as well as individualized therapies are necessary to reduce the mortality of breast cancer, and personalized patient care strategies rely on novel prognostic or predictive factors. In this study, with six breast cancer patients, 2D gel analysis was applied for studying protein expression differences in order to distinguish invasive ductal breast carcinoma, the most frequent breast tumor subtype, from control samples. In total, 1203 protein spots were assembled in a 2D reference gel. Differentially abundant spots were subjected to peptide mass fingerprinting for protein identification. Twenty proteins with their corresponding 38 differentially expressed 2D gel spots were contained in our previously reported proteome signature, suggesting that distinct protein forms were contributing. In-depth MS/MS measurements enabled analyses of protein structure details of selected proteins. In protein spots that significantly contributed to our signature, we found that glyceraldehyde-3-phosphate dehydrogenase was N-terminally truncated, pyruvate kinase M2 and nucleoside diphosphate kinase A but not other isoforms of these proteins were of importance, and nucleophosmin phosphorylation at serine residues 106 and 125 were clearly identified. Principle component analysis and hierarchical clustering with normalized quantitative data from the 38 spots resulted in accurate separation of tumor from control samples. Thus, separation of tissue samples as in our initial proteome signature could be confirmed even with a different proteome analysis platform. In addition, detailed protein structure investigations enabled refining our proteome signature for invasive ductal breast carcinoma, opening the way to structure-/function studies with respect to disease processes and/or therapeutic intervention.

  13. Neuroendocrine carcinoma of the pancreas with similar genetic alterations to invasive ductal adenocarcinoma.

    PubMed

    Kimura, Tetsuo; Miyamoto, Hiroshi; Fukuya, Akira; Kitamura, Shinji; Okamoto, Koichi; Kimura, Masako; Muguruma, Naoki; Ikemoto, Tetsuya; Shimada, Mitsuo; Yoneda, Akiko; Bando, Yoshimi; Takishita, Makoto; Takayama, Tetsuji

    2016-08-01

    Neuroendocrine carcinoma (NEC) of the pancreas is very rare, and its origin is not fully elucidated. Here, we present a case of a small-size NEC of the pancreas that is genetically similar to invasive ductal adenocarcinoma (IDA). A 65-year-old man was referred to our hospital due to obstructive jaundice and found to have a 12-mm solid tumor in the pancreas head. The tumor exhibited low vascularity on enhanced computed tomography, and endoscopic retrograde pancreatographic imaging revealed an irregular obstruction in a branch duct of the pancreas. The patient was thereby diagnosed with a pancreatic ductal cancer, and stomach-preserving pancreaticoduodenectomy with regional lymph node resection was performed. Histochemical analysis of the resected tumor showed that the neoplastic cells with scanty cytoplasm and hyperchromatic nuclei strongly expressed chromogranin A and synaptophysin. The Ki-67 index was 40 % in the most proliferative tumor regions, and the tumor was diagnosed as a NEC of the pancreas. However, in the analysis of genetic alterations of the tumor tissue, the neoplastic cells showed altered KRAS, TP53, and SMAD4/DPC4, suggesting that the NEC in our case is genetically related to IDA. Our data suggest that poorly differentiated IDAs may transform into NECs.

  14. [A Case of Invasive Ductal Carcinoma in the Fat Replacement of the Pancreatic Body and Tail].

    PubMed

    Ebihara, Takeshi; Yamamoto, Tameyoshi; Hoshino, Hiromitsu; Yoshimura, Jumpei; Sasamatsu, Shingo; Hiraki, Yoko; Nishi, Hidemi; Shimizu, Katsushu; Kawada, Masahiro; Inoue, Toshiya; Kato, Fumitaka; Amano, Koji; Mikami, Jota; Yamamura, Jun; Makari, Yoichi; Nakata, Ken; Ikeda, Naoki; Kamigaki, Shunji; Tsujie, Masaki; Kimura, Yutaka; Nakata, Yasuki; Munakata, Satoru; Ohzato, Hiroki

    2015-11-01

    A 56 year-old woman with obesity (BMI3 2) and diabetes mellitus was diagnosed with right renal cell carcinoma. She underwent right nephrectomy 1 year ago. Seven months after surgery, CT revealed a rapidly growing mass near the spleen. The mass showed slight accumulation of FDG (SUVmax=2.4) on PET-CT. Since the lesion grew rapidly and was not enhanced in the early phase of enhanced CT, we diagnosed pancreatic cancer. Distal pancreatectomy and splenectomy were performed. The final pathological diagnosis was invasive ductal carcinoma in the fat replacement of the pancreatic body and tail. Postoperatively, the patient had no complications such as pancreatic fistula or aggravation of glucose intolerance. She received postoperative chemotherapy with gemcitabine. Since she developed pulmonary artery thrombosis, postoperative chemotherapy was interrupted after 8 courses. Thirty-two months after the surgery, she was still living without any recurrence. Acinar cells were absent in the fat replacement of the pancreas, but the pancreatic duct cells were still present. There was carcinoma in situ in the main pancreatic duct surrounding chronic inflammation. Fat replacement itself could be potentially precursor of the pancreatic cancer.

  15. Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer.

    PubMed

    Pang, Jia-Min B; Savas, Peter; Fellowes, Andrew P; Mir Arnau, Gisela; Kader, Tanjina; Vedururu, Ravikiran; Hewitt, Chelsee; Takano, Elena A; Byrne, David J; Choong, David Yh; Millar, Ewan Ka; Lee, C Soon; O'Toole, Sandra A; Lakhani, Sunil R; Cummings, Margaret C; Mann, G Bruce; Campbell, Ian G; Dobrovic, Alexander; Loi, Sherene; Gorringe, Kylie L; Fox, Stephen B

    2017-07-01

    The spectrum of genomic alterations in ductal carcinoma in situ (DCIS) is relatively unexplored, but is likely to provide useful insights into its biology, its progression to invasive carcinoma and the risk of recurrence. DCIS (n=20) with a range of phenotypes was assessed by massively parallel sequencing for mutations and copy number alterations and variants validated by Sanger sequencing. PIK3CA mutations were identified in 11/20 (55%), TP53 mutations in 6/20 (30%), and GATA3 mutations in 9/20 (45%). Screening an additional 91 cases for GATA3 mutations identified a final frequency of 27% (30/111), with a high proportion of missense variants (8/30). TP53 mutations were exclusive to high grade DCIS and more frequent in PR-negative tumors compared with PR-positive tumors (P=0.037). TP53 mutant tumors also had a significantly higher fraction of the genome altered by copy number than wild-type tumors (P=0.005), including a significant positive association with amplification or gain of ERBB2 (P<0.05). The association between TP53 mutation and ERBB2 amplification was confirmed in a wider DCIS cohort using p53 immunohistochemistry as a surrogate marker for TP53 mutations (P=0.03). RUNX1 mutations and MAP2K4 copy number loss were novel findings in DCIS. Frequent copy number alterations included gains on 1q, 8q, 17q, and 20q and losses on 8p, 11q, 16q, and 17p. Patterns of genomic alterations observed in DCIS were similar to those previously reported for invasive breast cancers, with all DCIS having at least one bona fide breast cancer driver event. However, an increase in GATA3 mutations and fewer copy number changes were noted in DCIS compared with invasive carcinomas. The role of such alterations as prognostic and predictive biomarkers in DCIS is an avenue for further investigation.

  16. Prediction of occult invasive disease in ductal carcinoma in situ using computer-extracted mammographic features

    NASA Astrophysics Data System (ADS)

    Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

    2017-03-01

    Predicting the risk of occult invasive disease in ductal carcinoma in situ (DCIS) is an important task to help address the overdiagnosis and overtreatment problems associated with breast cancer. In this work, we investigated the feasibility of using computer-extracted mammographic features to predict occult invasive disease in patients with biopsy proven DCIS. We proposed a computer-vision algorithm based approach to extract mammographic features from magnification views of full field digital mammography (FFDM) for patients with DCIS. After an expert breast radiologist provided a region of interest (ROI) mask for the DCIS lesion, the proposed approach is able to segment individual microcalcifications (MCs), detect the boundary of the MC cluster (MCC), and extract 113 mammographic features from MCs and MCC within the ROI. In this study, we extracted mammographic features from 99 patients with DCIS (74 pure DCIS; 25 DCIS plus invasive disease). The predictive power of the mammographic features was demonstrated through binary classifications between pure DCIS and DCIS with invasive disease using linear discriminant analysis (LDA). Before classification, the minimum redundancy Maximum Relevance (mRMR) feature selection method was first applied to choose subsets of useful features. The generalization performance was assessed using Leave-One-Out Cross-Validation and Receiver Operating Characteristic (ROC) curve analysis. Using the computer-extracted mammographic features, the proposed model was able to distinguish DCIS with invasive disease from pure DCIS, with an average classification performance of AUC = 0.61 +/- 0.05. Overall, the proposed computer-extracted mammographic features are promising for predicting occult invasive disease in DCIS.

  17. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    SciTech Connect

    Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

    2007-11-01

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

  18. An atypical presentation of infiltrating ductal carcinoma

    PubMed Central

    Jha, Kunal Kishor; Gupta, Suresh Kumar

    2016-01-01

    A 64-year-old African-American female presented with nonbloody nipple discharge. Clinical and cytological examination of the discharge was normal. The mammography suggested pleomorphic calcification in the left breast. A stereotactic biopsy showed ductal carcinoma in situ and her estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2-neu receptor were negative. We removed the tumor tissue through lumpectomy and found that the mass was invasive ductal carcinoma. This case report highlights invasive ductal carcinoma, presenting with unilateral nipple discharge.

  19. Low-grade ductal carcinoma in situ and invasive mammary carcinoma with columnar cell morphology arising in a complex fibroadenoma in continuity with columnar cell change and flat epithelial atypia.

    PubMed

    Petersson, Fredrik; Tan, Puay Hoon; Putti, Thomas Choudary

    2010-10-01

    We describe the clinicopathologic features of a small low-grade invasive mammary carcinoma with cytomorphological columnar cell features arising in a complex fibroadenoma that in addition to sclerosing adenosis, apocrine metaplasia, and usual ductal hyperplasia also displayed columnar cell change with flat epithelial atypia and low-grade ductal carcinoma in situ merging with the invasive carcinoma. There were strong cytomorphological similarities between the invasive carcinoma and the low-grade ductal carcinoma in situ, which also showed significant overlap in the immunohistochemical findings.

  20. Invasive ductal breast carcinoma detector that is robust to image magnification in whole digital slides

    PubMed Central

    Balazsi, Matthew; Blanco, Paula; Zoroquiain, Pablo; Levine, Martin D.; Burnier, Miguel N.

    2016-01-01

    Abstract. Invasive ductal breast carcinomas (IDBCs) are the most frequent and aggressive subtypes of breast cancer, affecting a large number of Canadian women every year. Part of the diagnostic process includes grading the cancerous tissue at the microscopic level according to the Nottingham modification of the Scarff-Bloom-Richardson system. Although reliable, there exists a growing interest in automating the grading process, which will provide consistent care for all patients. This paper presents a solution for automatically detecting regions expressing IDBC in images of microscopic tissue, or whole digital slides. This represents the first stage in a larger solution designed to automatically grade IDBC. The detector first tessellated whole digital slides, and image features were extracted, such as color information, local binary patterns, and histograms of oriented gradients. These were presented to a random forest classifier, which was trained and tested using a database of 66 cases diagnosed with IDBC. When properly tuned, the detector balanced accuracy, F1 score, and Dice’s similarity coefficient were 88.7%, 79.5%, and 0.69, respectively. Overall, the results seemed strong enough to integrate our detector into a larger solution equipped with components that analyze the cancerous tissue at higher magnification, automatically producing the histopathological grade. PMID:27226977

  1. [Synchronous and ipsilateral invasive ductal carcinoma of the breast occurring near a phyllodes tumor - a case report].

    PubMed

    Nagashima, Saki; Sakurai, Kenichi; Suzuki, Shuhei; Sakagami, Masashi; Enomoto, Katsuhisa; Amano, Sadao; Koshinaga, Tsugumichi

    2014-11-01

    We report 2 cases of invasive ductal carcinoma of the breast occurring near a phyllodes tumor. The first case was ofa 58- year-old woman who had a tumor in her right breast and visited our hospital. Following a core needle biopsy (CNB), a malignant phyllodes tumor was diagnosed. We performed a lumpectomy for the phyllodes tumor, with 1.5-cm surgical margins. Pathological diagnosis of the resected specimen confirmed the malignant phyllodes tumor. A ductal carcinoma in situ (DCIS) was also discovered near the phyllodes tumor. The second case was of another 58-year-old woman who had a big tumor in her right breast and visited our hospital. CNB resulted in pathological diagnosis ofa benign phyllodes tumor. The tumor was removed by a lumpectomy with 1.5-cm surgical margins. The pathological diagnosis from the resected specimen was borderline phyllodes tumor with invasive ductal carcinoma in the proximity. In both cases, DCIS could not have been diagnosed preoperatively.

  2. 1H MR spectroscopy of invasive ductal carcinoma: correlations with FDG PET and histologic prognostic factors.

    PubMed

    Tozaki, Mitsuhiro; Hoshi, Kazuei

    2010-05-01

    The purpose of this article is to assess the histologic prognostic relevance of choline levels obtained using (1)H MR spectroscopy with a 1.5-T MR unit in patients with invasive breast cancer and to compare the observed choline levels with the standardized uptake value obtained using FDG PET. Single-voxel (1)H MR spectroscopy and PET/CT were performed for 50 patients with invasive ductal carcinoma (1.5-3 cm in size). The normalized choline signal was calculated using an external standard method. Proton MR spectroscopy detected the presence of choline in 44 cases. The average normalized choline signal was 1.1 (range, 0-3.9). The average standardized uptake value was 6.5 (range, 1.1-23). The correlation (r) between the normalized choline signal and the standardized uptake value was 0.52 (p < 0.0001). The normalized choline signal was significantly correlated with nuclear grade (p = 0.0002), triple-negative breast cancer status (p = 0.0009), and estrogen receptor negativity (p = 0.007). The standardized uptake value was significantly correlated with nuclear grade (p = 0.0002), estrogen receptor negativity (p = 0.002), and triple-negative breast cancer status (p = 0.009). No significant differences were found between the progesterone receptor-positive and negative groups or between the human epidermal growth factor receptor 2-positive and negative groups. The choline levels obtained using (1)H MR spectroscopy with a 1.5-T unit were well correlated with the standardized uptake value obtained using PET/CT and with the histologic prognostic parameters (nuclear grade, estrogen receptor status, and triple-negative lesion status).

  3. A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population

    PubMed Central

    2014-01-01

    Background To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma (ILC) patients compared to invasive ductal carcinoma (IDC) patients according to their molecular subtype. Methods We compared the clinicopathological characteristics, breast cancer-specific survival (BCSS) and overall survival (OS) between patients with IDC (n = 14,547) and ILC (n = 528). Results The ILC presented with a larger tumor size, more advanced cancer stage, increased rate of hormonal receptor positivity, human epidermal growth factor 2 (HER2) negativity and mastectomy than the IDC. The ILC patients more frequently presented with the luminal A subtype, whereas the IDC patients more frequently presented with the luminal B, HER2-overexpression, or triple negative subtype. The BCSS and OS were not significantly different between the IDC and ILC for each molecular subtype. Conclusions Similar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients. PMID:24621330

  4. Correlation between Ultrasound Findings of Tumor Margin and Clinicopathological Findings in Patients with Invasive Ductal Carcinoma of the Breast

    PubMed Central

    Sannomiya, Naoko; Hattori, Yuiko; Ueda, Naoyuki; Kamida, Akira; Koyanagi, Yuki; Nagira, Haruki; Ikunishi, Saeko; Shimabayashi, Kenta; Hashimoto, Yuki; Murata, Aya; Sato, Kengo; Hirooka, Yumi; Hosoya, Keiko; Ishiguro, Kiyosuke; Murata, Yoko; Hirooka, Yasuaki

    2016-01-01

    Background Breast ultrasound findings regarding tumor margins are crucial in judging whether a tumor is malignant or benign. However, the relationships between the margins and clinicopathological characteristics remain largely unknown. In this study, we examined the clinicopathological characteristics of patients with invasive ductal carcinoma whose ultrasound images showed either well-defined and rough or indistinct margins. Methods Of all consecutive patients diagnosed with invasive ductal carcinoma at the Division of Breast and Endocrine Surgery of Tottori University Hospital from January 2012 to December 2014, 122 patients whose ultrasound images showed either “well-defined and rough” or “indistinct” tumor margins were included in this study. Mammography and ultrasound images taken at the initial examination were reviewed. Patients were divided into two groups based on ultrasound findings of the tumor margins: the “well-defined and rough group” and the “indistinct group.” The relationships among ultrasound findings, mammography findings and clinicopathological findings were investigated in the two groups. Results The well-defined and rough group was more likely to contain solid-tubular carcinoma, while the indistinct group was more likely to contain scirrhous carcinoma. The MIB-1 index was higher in the well-defined and rough group than in the indistinct group. Additionally, the proportion of patients with nuclear grade 3, estrogen receptor-negative/progesterone receptor-negative, and triple-negative breast cancer was greater in the well-defined and rough group than in the indistinct group. Conclusion Invasive ductal carcinomas with well-defined and rough margins on ultrasound were likely to be malignant and proliferative than those with indistinct margins. PMID:27493488

  5. Differential ezrin and phosphorylated ezrin expression profiles between pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and invasive ductal carcinoma of the pancreas.

    PubMed

    Oda, Yasunori; Aishima, Shinichi; Morimatsu, Katsuya; Hayashi, Akifumi; Shindo, Koji; Fujino, Minoru; Mizuuchi, Yusuke; Hattori, Masami; Tanaka, Masao; Oda, Yoshinao

    2013-08-01

    Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanINs) are important premalignant lesions of pancreatic cancer. Ezrin is a member of the ezrin, radixin, and moesin protein family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton. We investigated the roles of ezrin during carcinogenesis in IPMN and invasive ductal carcinoma and examined whether ezrin was a prognostic factor. We examined ezrin and phosphorylated ezrin (p-ezrin) expression in 131 IPMNs, 47 PanINs, and 59 invasive ductal carcinomas by immunohistochemical staining. Ezrin and p-ezrin (tyr354) expressions were significantly higher in IPMN with an associated invasive carcinoma, compared with those in IPMN with high-grade dysplasia (P = .03 and P = .0007, respectively). In all grades of PanINs, ezrin and p-ezrin (tyr353) were highly expressed. In patients with invasive ductal carcinoma, the presence of PanIN-2 or PanIN-3 was significantly correlated with positive ezrin and p-ezrin (tyr353) expression of the invasive ductal carcinoma component (P = .01 and P = .0004). The negative p-ezrin (tyr353) expression group of invasive ductal carcinoma showed a significantly worse prognosis than did the positive p-ezrin (tyr353) expression group by survival analysis (P = .04) and was a statistically significant adverse prognostic factor by both univariate and multivariate analyses (P = .048 and P = .015). Ezrin phosphorylation sites differ between the developments of IPMN and PanIN. Although p-ezrin (tyr354) expression in IPMNs is associated with tumor invasion, p-ezrin (tyr353) expression in invasive ductal carcinoma plays an important role not in tumor invasion and metastasis but in the early development of PanINs.

  6. Clinicopathological characteristics of mucinous carcinoma of the breast in Korea: comparison with invasive ductal carcinoma-not otherwise specified.

    PubMed

    Park, Seho; Koo, Jaseung; Kim, Joo-Hee; Yang, Woo Ick; Park, Byeong-Woo; Lee, Kyong Sik

    2010-03-01

    Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.

  7. Automatic detection of invasive ductal carcinoma in whole slide images with convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Cruz-Roa, Angel; Basavanhally, Ajay; González, Fabio; Gilmore, Hannah; Feldman, Michael; Ganesan, Shridar; Shih, Natalie; Tomaszewski, John; Madabhushi, Anant

    2014-03-01

    This paper presents a deep learning approach for automatic detection and visual analysis of invasive ductal carcinoma (IDC) tissue regions in whole slide images (WSI) of breast cancer (BCa). Deep learning approaches are learn-from-data methods involving computational modeling of the learning process. This approach is similar to how human brain works using different interpretation levels or layers of most representative and useful features resulting into a hierarchical learned representation. These methods have been shown to outpace traditional approaches of most challenging problems in several areas such as speech recognition and object detection. Invasive breast cancer detection is a time consuming and challenging task primarily because it involves a pathologist scanning large swathes of benign regions to ultimately identify the areas of malignancy. Precise delineation of IDC in WSI is crucial to the subsequent estimation of grading tumor aggressiveness and predicting patient outcome. DL approaches are particularly adept at handling these types of problems, especially if a large number of samples are available for training, which would also ensure the generalizability of the learned features and classifier. The DL framework in this paper extends a number of convolutional neural networks (CNN) for visual semantic analysis of tumor regions for diagnosis support. The CNN is trained over a large amount of image patches (tissue regions) from WSI to learn a hierarchical part-based representation. The method was evaluated over a WSI dataset from 162 patients diagnosed with IDC. 113 slides were selected for training and 49 slides were held out for independent testing. Ground truth for quantitative evaluation was provided via expert delineation of the region of cancer by an expert pathologist on the digitized slides. The experimental evaluation was designed to measure classifier accuracy in detecting IDC tissue regions in WSI. Our method yielded the best quantitative

  8. Epithelial cells captured from ductal carcinoma in situ reveal a gene expression signature associated with progression to invasive breast cancer

    PubMed Central

    Abuázar, Carolina Sens; de Toledo Osorio, Cynthia Aparecida Bueno; Pinilla, Mabel Gigliola; da Silva, Sabrina Daniela; Camargo, Anamaria Aranha; Silva, Wilson Araujo; e Ferreira, Elisa Napolitano; Brentani, Helena Paula; Carraro, Dirce Maria

    2016-01-01

    Breast cancer biomarkers that can precisely predict the risk of progression of non-invasive ductal carcinoma in situ (DCIS) lesions to invasive disease are lacking. The identification of molecular alterations that occur during the invasion process is crucial for the discovery of drivers of transition to invasive disease and, consequently, biomarkers with clinical utility. In this study, we explored differences in gene expression in mammary epithelial cells before and after the morphological manifestation of invasion, i.e., early and late stages, respectively. In the early stage, epithelial cells were captured from both pre-invasive lesions with distinct malignant potential [pure DCIS as well as the in situ component that co-exists with invasive breast carcinoma lesions (DCIS-IBC)]; in the late stage, epithelial cells were captured from the two distinct morphological components of the same sample (in situ and invasive components). Candidate genes were identified using cDNA microarray and rapid subtractive hybridization (RaSH) cDNA libraries and validated by RT-qPCR assay using new samples from each group. These analyses revealed 26 genes, including 20 from the early and 6 from the late stage. The expression profile based on the 20 genes, marked by a preferential decrease in expression level towards invasive phenotype, discriminated the majority of DCIS samples. Thus, this study revealed a gene expression signature with the potential to predict DCIS progression and, consequently, provides opportunities to tailor treatments for DCIS patients. PMID:27708222

  9. Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

    PubMed

    Hamada, Yoshihiro; Nakayama, Yoshifuku

    2017-08-19

    Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters <2 cm. The follow-up period of the 20 patients with smaller tumors was 1-24 years. The small-tumor group (n = 20) included 11 men and 9 women, aged 51-80 years. Five died of liver metastasis (LM group, n = 5) and 15 patients (non-LM group, n = 15) were either alive without recurrence (n = 11) or died of peritonitis carcinomatosa following local recurrence, subarachnoid hemorrhage, primary lung cancer, or old age (n = 1 for each cause of death). The LM and non-LM groups did not significantly differ in numbers of venous invasion by the carcinoma in IDCP and non-IDCP area of the pancreas. However, median numbers of invaded veins in the area of IDCP and percentage of invaded vein/total number of vein in IDCP area were significantly higher in the LM group. Among patients with small IDCP tumors, the LM group showed more aggressive venous invasion by IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  10. Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases.

    PubMed

    Aquino, Ranniere Gurgel Furtado DE; Vasques, Paulo Henrique Diógenes; Cavalcante, Diane Isabelle Magno; Oliveira, Ayane Layne DE Sousa; Oliveira, Bruno Masato Kitagawa DE; Pinheiro, Luiz Gonzaga Porto

    2017-01-01

    to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma. this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Ceará, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases. the mean patients'age was 56.81 years ± 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm ± 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001). elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases. analisar a relação das características anatomopatológicas com o comprometimento axilar em casos de carcinoma ductal invasor. estudo transversal de 220 pacientes com câncer de mama, submetidas à mastectomia radical ou quadrantectomia com esvaziamento axilar, oriundos do Serviço de Mastologia da Maternidade Escola Assis Chateaubriand, Ceará, Brasil. Os tumores foram submetidos a processamento histol

  11. Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast.

    PubMed

    Li, Zhenling; Liu, Qixiang; Piao, Junjie; Hua, Fenjian; Wang, Jing; Jin, Guang; Lin, Zhenhua; Zhang, Yan

    2016-08-25

    T-lymphoma invasion and metastasis-inducing protein 1 (Tiam1) has been implicated in tumor occurrence and progression. Recent studies have shown that high expression levels of Tiam1 protein appear to be associated with the progression of numerous human tumors. This study attempted to explore the role of Tiam1 protein in tumor progression and the prognostic evaluation of breast cancer. The localization of the Tiam1 protein was determined in the MDA-MB-231 breast cancer cell line using immunofluorescence (IF) staining. In addition, a total of 283 breast tissue samples, including 153 breast cancer tissues, 67 ductal carcinoma in situ (DCIS) and 63 adjacent non-tumor breast tissues, were analyzed by immunohistochemical (IHC) staining of the Tiam1 protein. The correlation between Tiam1 expression and clinicopathological characteristics was evaluated by Chi-square test and Fisher's exact tests. Disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier method. Additionally, univariate and multivariate analyses were performed by the Cox proportional hazards regression models. Tiam1 protein showed a mainly cytoplasmic staining pattern in breast cancer cells; however, nuclear staining was also observed. Tiam1 protein expression was significantly higher in breast cancers (42.5 %, 65/153) and DCIS (40.3 %, 27/67) than in adjacent non-tumor tissues (12.7 %, 8/63). In addition, Tiam1 associated with tumor stage and Ki-67 expression, but negatively correlated with receptor tyrosine-protein kinase erbB-2 (Her2) expression. Moreover, survival analyses showed that DFS and 10-year OS rates were significantly lower in breast cancer patients with high Tiam1 expression than those with low Tiam1 expression. Univariate analysis suggested that molecular types, clinical stage, Her2 expression levels and Tiam1 expression levels were also significantly associated with DFS and 10-year OS rates of breast cancer patients. Furthermore, multivariate

  12. Correlation of HER2 overexpression with gene amplification and its relation to chromosome 17 aneuploidy: a 5-year experience with invasive ductal and lobular carcinomas.

    PubMed

    Nassar, Aziza; Khoor, Andras; Radhakrishnan, Reshmitha; Radhakrishnan, Anu; Cohen, Cynthia

    2014-01-01

    The HER2 oncogene shows expression or amplification, or both, in approximately 15% to 20% of breast cancers and has been associated with poor prognosis and a response to trastuzumab therapy. HER2 gene status determines the eligibility of breast cancer patients for trastuzumab therapy and a large fraction (41-56%) of these patients respond to targeted therapy. Several studies have related the increased expression of HER2 to an increased copy number of chromosome 17, rather than amplification of the HER2 gene. We compared the results of immunohistochemistry and fluorescence in situ hybridization in both invasive ductal and invasive lobular carcinomas, to determine the frequency of chromosome 17 aneuploidy associated with discordant results. In total, 390 invasive ductal carcinomas and 180 invasive lobular carcinomas diagnosed from January 2000 to December 2005 were included in the study only if results were available for immunohistochemistry (HercepTest; DAKO, Carpinteria, California) and fluorescence in situ hybridization (PathVysion HER2 DNA Probe Kit; Abbott Laboratories, Des Plaines, Illinois). Tumors classified as invasive ductal carcinomas were graded according to the Bloom-Richardson grading system. Correlation between the results of immunohistochemistry and fluorescence in situ hybridization was performed for all categories. Among invasive ductal carcinomas, 29% (115/390) showed chromosome 17 aneuploidy, mostly associated with grade 3/HER2 2+ (45%) or grade 2/HER2 3+ (55%) that were not amplified. Also, 34% (12/35) of invasive lobular carcinomas showed chromosome 17 aneuploidy; approximately one-third of these cases were HER2 2+ (33%) and HER2 3+ (37%) that were not amplified. Discordance between the results of immunohistochemistry and fluorescence in situ hybridization in both ductal and lobular carcinomas is largely associated with chromosome 17 aneuploidy.

  13. Necrotizing granulomatous inflammation in an ipsilateral axillary lymph node in a patient with invasive ductal carcinoma of the breast.

    PubMed

    Yang, Limin; Park, Jeong Mi; Askeland, Ryan W; Fajardo, Laurie L

    2012-01-01

    A patient presented with flu-like symptoms and a warm, tender area in the left axilla after working with an ancient piece of Cyprus wood. Antibiotics prescribed failed to improve symptoms. Followup physical examination and subsequent ultrasound found suspicious left-breast mass and an enlarged lymph node in the left axilla. Biopsy and lumpectomy of the left-breast mass revealed invasive ductal carcinoma. Biopsy and excision of the enlarged lymph node in the left axilla revealed necrotizing granulomatous inflammation without evidence of metastatic breast carcinoma. To our knowledge, this is the first case report to show the coexistence of breast cancer with necrotizing granulomatous inflammation in the ipsilateral axillary lymph node, likely due to exposure to ancient wood.

  14. Preoperative clinicopathologic factors and breast magnetic resonance imaging features can predict ductal carcinoma in situ with invasive components.

    PubMed

    Lee, Chih-Wei; Wu, Hwa-Koon; Lai, Hung-Wen; Wu, Wen-Pei; Chen, Shou-Tung; Chen, Dar-Ren; Chen, Chih-Jung; Kuo, Shou-Jen

    2016-04-01

    Ductal carcinoma in situ (DCIS) is a non-invasive cancerous breast lesion; however, from 10% to 50% of patients with DCIS diagnosed by core needle biopsy (CNB) or vacuum-assisted core biopsy (VACB) are shown to have invasive carcinoma after surgical excision. In this study, we evaluated whether preoperative clinicopathologic factors and breast magnetic resonance image (MRI) features are predictive of DCIS with invasive components before surgery. Patients comprised 128 adult women with a diagnosis of DCIS as determined by pathological analysis of CNB or VACB specimens and positive MRI findings who underwent breast surgery during the period January 2011 to December 2013 at the Changhua Christian Hospital. Clinicopathologic and breast MRI factors were compared between patients with postoperative pathology indicative of true DCIS and those with postoperative pathology showing DCIS with invasive components. Of the 128 patients with a preoperative diagnosis of DCIS, 73 (57.0%) had postoperative histopathologic evidence of true DCIS and 55 (43.0%) showed evidence of DCIS with invasive components. Results of statistical analyses revealed that MRI evidence of a mass-like lesion (P=0.025), nipple-areolar complex (NAC) invasion (P=0.029), larger tumor volume (P=0.010), larger maximum measurable apparent diffusion coefficient (ADC) area (P=0.039), heterogenous or rim enhancement pattern (P=0.010), as well as immunohistochemical evidence of human epidermal growth factor receptor 2 (HER-2) overexpression (P=0.010) were predictive of DCIS with an invasive component in postoperative surgical specimens. Invasive component should be considered in biopsy proven DCIS patients with preoperative MRI evidence of a mass-like lesion, nipple-areolar complex invasion, large tumor volume, a larger maximum measurable ADC area, or a rim or heterogenous enhancement pattern, as well as in patients with immunohistochemical evidence of HER-2 overexpression. Copyright © 2016 Elsevier Ireland Ltd

  15. Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis

    PubMed Central

    Zucchi, I.; Mento, E.; Kuznetsov, V. A.; Scotti, M.; Valsecchi, V.; Simionati, B.; Vicinanza, E.; Valle, G.; Pilotti, S.; Reinbold, R.; Vezzoni, P.; Albertini, A.; Dulbecco, R.

    2004-01-01

    Expression profiles of breast carcinomas are difficult to interpret when they are obtained from tissue in toto, which may contain a large proportion of non-cancer cells. To avoid this problem, we microscopically isolated cells from a primary invasive ductal carcinoma of the breast and from an axillary node harboring a metastatic breast carcinoma, to obtain pure populations of carcinoma cells (≈500) and used them for serial analysis of gene expression. The expression profiles generated from both populations of cells were compared with the profile of a disease-free mammary epithelium. We showed that the expression profiles obtained are exclusive of carcinoma cells with no contribution of non-epithelial cells. From a total of 16,939 unique tags analyzed, we detected 559 statistically significant changes in gene expression; some of these genes have not been previously associated with breast cancer. We observed that many of the down-regulated genes are the same in both cancers, whereas the up-regulated genes are completely different, suggesting that the down-regulation of a set of genes may be the basic mechanism of cancer formation, while the up-regulation may characterize and possibly control the state of evolution of individual cancers. The results obtained may help in characterizing the neoplastic process of breast cancer. PMID:15608061

  16. Psychosocial distress affecting patients with ductal carcinoma in situ compared to patients with early invasive breast cancer.

    PubMed

    Sanders, Judith Brown; Loftin, Adam; Seda, Julia S; Ehlenbeck, Chris

    2014-12-01

    Psychological distress in patients with a diagnosis of ductal carcinoma in situ (DCIS) or early invasive breast cancer (EIBC) can emanate from perceived risk of recurrence and is accompanied by perceived risk of death from the diseases. These factors can impart a lower quality of life that can result in poorer health outcomes. In addition, inaccurate risk perceptions can have an effect on decision making, psychosocial outcomes, and subsequent health behaviors. The purpose of this study is to assess patients with DCIS and EIBC and their perceived risk of recurrence and perceived risk of dying, and evaluate their outlook for the future, the degree of social support from spouses and significant others of patients who have been diagnosed with DCIS and EIBC, and the relationship to the patient's perceived risk perception of recurrence and dying from the diseases.

  17. Methylation status and overexpression of COX-2 in Tunisian patients with ductal invasive breast carcinoma.

    PubMed

    Karray-Chouayekh, Sondes; Trifa, Fatma; Khabir, Abdelmajid; Boujelbene, Noureddine; Sellami-Boudawara, Tahia; Daoud, Jamel; Frikha, Mounir; Gargouri, Ali; Mokdad-Gargouri, Raja

    2011-06-01

    Inflammation and hormonal signalling induce the cyclooxygenase-2 (COX-2) expression in solid tumours including breast cancer, which in turn affects cell proliferation, apoptosis and metastasis. The aim of this study was to investigate the expression of COX-2 and its association with clinical parameters, patient's survival, hormones receptors (oestrogen, progesterone), ERBB2 and TP53 expression in 83 cases of infiltrating ductal breast carcinomas. Moreover, the methylation status at the CpG islands of the COX-2 gene promoter was also explored in 70 specimens. We showed that tumours exhibiting moderate to intense COX-2 immunostaining were significantly more frequent in patients over 45 years old (p = 0.027). Moreover, a high level of COX-2 expression correlated with a shorter survival time (p log-rank = 0.04) and was an independent prognostic factor (p = 0.022; HR 6.4; 95% CI = 1.3-31.4). On the other hand, hypermethylation of the COX-2 gene promoter was observed in 27% of cases and strongly associated with smaller tumours (<5 cm, p = 0.011). Furthermore, patients with methylated COX-2 pattern have a better 4-year disease-free survival (p = 0.022) as well as a prolonged overall survival (p log-rank test = 0.034). In conclusion, we showed that high COX-2 expression was associated with reduced survival and was an independent prognostic factor. However, hypermethylation of the COX-2 promoter correlated with a better overall survival in Tunisian patients with breast carcinoma.

  18. Distinction of Invasive Carcinoma Derived From Intraductal Papillary Mucinous Neoplasms From Concomitant Ductal Adenocarcinoma of the Pancreas Using Molecular Biomarkers.

    PubMed

    Tamura, Koji; Ohtsuka, Takao; Date, Kenjiro; Fujimoto, Takaaki; Matsunaga, Taketo; Kimura, Hideyo; Watanabe, Yusuke; Miyazaki, Tetsuyuki; Ohuchida, Kenoki; Takahata, Shunichi; Ishigami, Kousei; Oda, Yoshinao; Mizumoto, Kazuhiro; Nakamura, Masafumi; Tanaka, Masao

    2016-07-01

    To clarify the usefulness of molecular biomarkers for distinguishing invasive carcinoma derived from intraductal papillary mucinous neoplasms (IPMNs [Inv-IPMN]) from concomitant pancreatic ductal adenocarcinoma (PDAC). Data from 19 patients with resected concomitant PDAC were retrospectively reviewed. KRAS/GNAS mutations and immunohistochemical (IHC) expression of p53 and p16/CDKN2A were assessed in both IPMN and distinct PDAC. As controls, KRAS/GNAS mutations and IHC labeling were assessed between invasive and noninvasive components in 1 lesion of 22 independent patients. KRAS/GNAS mutation status of invasive and noninvasive components in Inv-IPMN was consistent in 18 (86%) of 21 patients. Conversely, mutational patterns in IPMN and distinct PDAC in the same pancreas differed from each other in 17 (89%) of 19. There were 10 (53%) and 8 (42%) of 19 patients who showed the same p53 and p16/CDKN2A staining between concomitant PDAC and distinct IPMN. In the Inv-IPMN cohort, 19 (86%) of 22 patients showed the same IHC expression pattern between the noninvasive and invasive components. It may be possible to distinguish Inv-IPMN from concomitant PDAC by assessing these molecular biomarkers. More precise distinction of Inv-IPMN and concomitant PDAC will lead to adequate recognition of the natural history of IPMNs and hence optimal management.

  19. Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.

    PubMed

    Yagmurdur, M C; Atac, F B; Tutar, N U; Verdi, H; Isiklar, I; Ozdemir, B H; Ozbek, N; Karakayali, H; Haberal, M

    2008-01-01

    The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.

  20. High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression.

    PubMed

    Sun, Xian-Fu; Shao, Ying-Bo; Liu, Ming-Ge; Chen, Qi; Liu, Zhao-Jun; Xu, Bin; Luo, Su-Xia; Liu, Hui

    2017-05-01

    Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

  1. The First Case of HER2+ Invasive Ductal Carcinoma Arising From a Breast Hamartoma and Literature Review.

    PubMed

    Baer, Lea; Rogers, Sherise Chantell; Farrelly, Patricia; Tornos, Carmen; Sweeney, Keith

    2017-01-01

    Carcinomas arising from breast hamartomas are exceedingly rare. We present the first reported case of an African-American female presenting with a right breast lump and a subsequent mammogram suggestive of a hamartoma. She later underwent lumpectomy and was found to have HER2+ invasive ductal carcinoma (IDC) arising from a hamartoma. She was amenable to HER2-targeted trastuzumab, hormone therapy and adjuvant radiation but declined chemotherapy. In a review of the literature, IDC is the predominant neoplastic type found in hamartomas. The average hamartoma size at time of neoplasm diagnosis is 6.0 cm. Patients with hamartomas greater than 6.0 cm, with changes in calcification pattern; new nodules or asymmetry should be considered for additional evaluation with ultrasound, MRI and/or biopsy. HER2 status is under-reported among cases and should be evaluated in any malignancy found within hamartomas as HER-2 therapy has improved overall survival and recurrence free survival in HER2+breast cancer patients.

  2. SPARC (osteonectin) in breast tumors of different histologic types and its role in the outcome of invasive ductal carcinoma.

    PubMed

    Hsiao, Yi-Hsuan; Lien, Huang-Chun; Hwa, Hsiao-Lin; Kuo, Wen-Hung; Chang, King-Jen; Hsieh, Fon-Jou

    2010-01-01

    The purpose of this study was to characterize the immunohistochemical distribution of secreted protein acidic and rich in cystein (SPARC) in benign and malignant breast tumors of different histologic types and define its association with the outcome of invasive ductal carcinoma (IDC) patients. A total of 286 samples of benign and malignant breast lesions between 1994 and 2005 were retrieved from National Taiwan University Hospital. Up to 11 years clinical follow-up data were available for 185 patients with IDC. Immunohistochemistry staining with SPARC was performed in tissue microarray or whole section. The association of expression of SPARC and cumulative overall survival of IDC patients were analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Secreted protein acidic and rich in cystein was not expressed in benign breast phylloides and all benign breast tumors, while expressed in 17.2% of IDC, 85% of metaplastic carcinoma of the breast (MCB), and all malignant breast phylloides. Secreted protein acidic and rich in cystein was strongly expressed in mesenchymal components of MCB and expression levels in epithelial components were variable. The correlation of positive expression of SPARC and poor long-term survival in IDC is significant (p = 0.004). Individuals with positive SPARC expression had 2.34 times higher hazard of death compared with those with negative SPARC expression after adjusting for factors including positive lymph node, TNM tumor stage, estrogen receptor, and progesterone receptor. Secreted protein acidic and rich in cystein may be useful as a prognostic indicator for IDC.

  3. Synchronous bilateral non-Hodgkin’s diffuse large B-cell lymphoma of the breast and left breast invasive ductal carcinoma: a case report and review of literature

    PubMed Central

    Liu, Weihua; Zhu, Hong; Zhou, Xiaoge

    2014-01-01

    Lymphoma of the breast is unusual, and synchronous bilateral lymphoma and carcinoma of the breast is extremely rare. We present the case of a 51-year-old woman who found a mass in her left breast. Ultrasound scan findings revealed nodules at the 2 o’clock position in her left breast and focal dilation of the duct at the 8-9 o’clock and 10 o’clock position in her right and left breasts, respectively. A left breast ultrasound-guided core needle biopsy and right breast segmental excisional biopsy were performed. Pathological and immunohistochemical examination revealed left breast invasive ductal carcinoma and right breast diffuse large B-cell lymphoma of the non-germinal center type. Pathological examination of the left breast modified radical mastectomy specimen revealed synchronous invasive ductal carcinoma (grade III) and diffuse large B-cell lymphoma. The patient received chemotherapy and bone marrow transplantation in another hospital. Based on a review of the relevant literature, we discuss the diagnosis, clinical features, treatment, and prognosis of synchronous breast lymphoma and invasive ductal carcinoma. PMID:25400793

  4. Significance of HER2 protein examination in ductal carcinoma in situ.

    PubMed

    Horimoto, Yoshiya; Tokuda, Emi; Arakawa, Atsushi; Kosaka, Taijiro; Saito, Mitsue; Kasumi, Fujio

    2011-05-15

    HER2 expression is routinely checked in ductal carcinoma in situ, as in invasive ductal carcinoma. However, the effect of HER2 status in ductal carcinoma in situ on the development of malignancy and the significance of overexpression of HER2 are still not clear. We experienced 103 cases that were diagnosed as pure ductal carcinoma in situ from operative specimens in the 2-y period from 2006 to 2007. We examined their HER2 status and other markers. We added 38 cases of ductal carcinoma in situ with small invasive disease 5mm or less in diameter as subjects. We also examined how accurately HER2 status in biopsy specimens predicted the existence of an invasive component. In pure ductal carcinoma in situ, tumors that were comedo type, high grade, or ER negative showed a high frequency of HER2 overexpression. In cases with small invasion, HER2 expression was higher than that in pure ductal carcinoma in situ. Among cases that were diagnosed as ductal carcinoma in situ by biopsy, 28% had invasive disease in operative specimens. In tumors that were palpable, large, or expressed HER2 3+ in biopsy samples, invasive disease was frequently observed in operative specimens. Overexpression of HER2 in ductal carcinoma in situ might not always be necessary for progression to invasive ductal carcinoma. To clarify the significance of HER2 examination in DCIS, further investigations of the potential for invasive ductal carcinoma and the prognosis are still needed. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Evaluation of Apparent Diffusion Coefficient to Predict Grade, Microinvasion, and Invasion in Ductal Carcinoma In Situ of the Breast.

    PubMed

    Hussein, Heba; Chung, Caroline; Moshonov, Hadas; Miller, Naomi; Kulkarni, Supriya R; Scaranelo, Anabel M

    2015-12-01

    To evaluate the role of apparent diffusion coefficient (ADC) in distinguishing ductal carcinoma in situ (DCIS) grades and identifying microinvasive and/or invasive disease in the preoperative evaluation of patients with core biopsy-proven DCIS. Research Ethics Board-approved study with informed consent from 81 women (age, 36-84 years) scheduled for core-biopsy with results of 82 noninvasive breast carcinomas. All patients were assessed preoperatively by diffusion sequence in addition to contrast magnetic resonance imaging (MRI). Lesion morphology and ADC values were recorded. The Kruskal-Wallis or one-way analysis of variance test and Pearson correlation coefficient were used to study the association between ADC and MRI lesion characteristics. Logistic regression analysis was used to evaluate the ability of ADC to predict the presence of invasion. Surgical pathology demonstrated associated invasive cancer in 26.8%, microinvasion in 14.6%, and pure DCIS in 58.5%. The minimum regions of interest (ROI)-based ADC was significantly different among the following three groups (P < .001, Kruskal-Wallis test): 0.98 × 10(-3) mm(2)/s ± 0.25 for pure DCIS, 0.82 × 10(-3) mm(2)/s ± 0.20 for DCIS with microinvasion, and 0.71 × 10(-3) mm(2)/s ± 0.27 for DCIS with invasive disease. Based on logistic regression analysis, the minimum ROI-based ADC of 0.56 × 10(-3) mm(2)/s was a significant predictor for invasive disease (odds ratio = 0.02, 95% confidence interval [0.002, 0.207], P = .001). Regardless of the field strength (1.5 vs. 3.0 T) ADC values of high-grade and non-high-grade DCIS were not significantly different. Pure DCIS had the highest "ROI-based" ADC measured using 1.5 T or 3.0 T. The ADC was able to identify microinvasion or invasive cancer in biopsy-proven DCIS lesions but not to distinguish the DCIS grades. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

  6. Sentinel node procedure is warranted in ductal carcinoma in situ with high risk of occult invasive carcinoma and microinvasive carcinoma treated by mastectomy.

    PubMed

    Tunon-de-Lara, Christine; Giard, Sylvia; Buttarelli, Max; Blanchot, Jérome; Classe, Jean-Marc; Baron, Marc; Monnier, Brice; Houvenaeghel, Gilles

    2008-01-01

    Axillary lymph node dissection in patients with ductal carcinoma in situ (DCIS) of the breast is not warranted because DCIS has no metastatic potential. However, the risk of microinvasive carcinoma (MIC) exists in large DCIS treated by mastectomy. The aim of this series is to evaluate the incidence of lymph node metastases in DCIS and DCIS-MIC. We analyzed retrospectively patients treated in six French cancer centers for pure DCIS or DCIS-MIC. Surgical procedures were lumpectomy or mastectomy associated with an axillary sentinel node (SN) procedure. We included 161 patients suffering from pure DCIS (116/161, 72%) or DCIS-MIC (45/161, 28%). Mean age was 56 years (32-78). We observed underestimation between core biopsy and histological result in 43/142 cases (30%). These data show an association between lesion size, solid subtype, high-grade DCIS, and underestimation. Forty-eight breast conservative procedures were performed and 113 mastectomies (70%). SN procedure was performed using blue dye, technetium, or both. In our series, we selected patients with a high risk of occult invasive carcinoma: high grade (55%), mean size (27 mm), and mastectomy (112). Six SN were found positive (3.7%). In the five patients treated with complete axillary dissection, the SN was the only positive node. SN in DCIS is an interesting procedure but not necessary for all patients. We need to focus on the subgroup with or a high risk of occult MIC: extensive calcifications or palpable mass, DCIS diagnosed by core biopsy and underestimation, multifocality, high grade, large tumor size, MIC, and mastectomy.

  7. Comparison of 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma

    PubMed Central

    Hogan, Molly P.; Goldman, Debra A.; Dashevsky, Brittany; Riedl, Christopher C.; Gönen, Mithat; Osborne, Joseph R.; Jochelson, Maxine; Hudis, Clifford; Morrow, Monica; Ulaner, Gary A.

    2016-01-01

    Although guidelines such as those of the National Comprehensive Cancer Network consider 18F-FDG PET/CT for systemic staging of newly diagnosed stage III breast cancer patients, factors in addition to stage may influence the utility of PET/CT. Because invasive lobular carcinoma (ILC) is less conspicuous than invasive ductal carcinoma (IDC) on 18F-FDG PET, we hypothesized that tumor histology may be one such factor. We evaluated PET/CT systemic staging of patients newly diagnosed with ILC compared with IDC. Methods In this Institutional Review Board–approved retrospective study, our Hospital Information System was screened for ILC patients who underwent PET/CT in 2006–2013 before systemic or radiation therapy. Initial stage was determined from examination, mammography, ultrasound, MR, or surgery. PET/CT was performed to identify unsuspected distant metastases. A sequential cohort of stage III IDC patients was evaluated for comparison. Upstaging rates were compared using the Pearson χ2 test. Results The study criteria were fulfilled by 146 ILC patients. PET/CT revealed unsuspected distant metastases in 12 (8%): 0 of 8 with initial stage I, 2 of 50 (4%) stage II, and 10 of 88 (11%) stage III. Upstaging to IV by PET/CT was confirmed by biopsy in all cases. Three of 12 upstaged patients were upstaged only by the CT component of the PET/CT, as the metastases were not 18F-FDG–avid. In the comparison stage III IDC cohort, 22% (20/89) of patients were upstaged to IV by PET/CT. All 20 demonstrated 18F-FDG–avid metastases. The relative risk of PET/CT revealing unsuspected distant metastases in stage III IDC patients was 1.98 times (95% confidence interval, 0.98–3.98) that of stage III ILC patients (P = 0.049). For 18F-FDG–avid metastases, the relative risk of PET/CT revealing unsuspected 18F-FDG–avid distant metastases in stage III IDC patients was 2.82 times (95% confidence interval, 1.26–6.34) that of stage III ILC patients (P = 0.007). Conclusion 18F

  8. Histological differences between invasive ductal carcinoma with a large central acellular zone and matrix-producing carcinoma of the breast.

    PubMed

    Sasaki, Yuka; Tsuda, Hitoshi; Ueda, Shigeto; Asakawa, Hideki; Seki, Kunihiko; Murata, Tetsuya; Kuriki, Ken; Tamai, Seiichi; Matsubara, Osamu

    2009-06-01

    Carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrix-producing carcinoma (MPC) have been recently noted as basal-like-type breast cancers, but the two entities are often confused. To clarify their histological differences, the histopathological sections of 15 CAC and seven MPC were examined and the following features were compared by reviewing slides: (i) mode of invasion; (ii) alteration of cancer cell adhesion in the transitional area between cellular and acellular zones; (iii) staining of the stromal matrix; (iv) lymphocyte infiltration; and (v) tumor grade. Complete agreement was required between two observers for the assessments of these features. All CAC had relatively sharp margins but showed infiltrative growth accompanied by eosinophilic intercellular matrix. In CAC there was abrupt transition between peripheral cellular and central acellular zones without alteration of cancer cell adhesion. In contrast, all MPC showed expansive growth with a well circumscribed margin, accompanied by basophilic and myxoid intercellular matrix. In MPC there was gradual transition from cellular to acellular areas with gradual loss of cancer cell adhesion. Histological grade 3 and peripheral lymphocyte infiltration were common features. It is suggested that CAC and MPC are histologically distinct entities, and that the aforementioned features are helpful for differential diagnosis.

  9. Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

    PubMed

    Papantoniou, Vassilios; Valsamaki, Pipitsa; Sotiropoulou, Evangelia; Tsaroucha, Angeliki; Tsiouris, Spyridon; Sotiropoulou, Maria; Marinopoulos, Spyridon; Kounadi, Evangelia; Karianos, Theodore; Fothiadaki, Athina; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Ptohis, Nikolaos; Makris, Nikolaos; Limouris, Georgios; Antsaklis, Aris

    2011-10-01

    The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

  10. Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast.

    PubMed

    Dallol, Ashraf; Buhmeida, Abdelbaset; Merdad, Adnan; Al-Maghrabi, Jaudah; Gari, Mamdooh A; Abu-Elmagd, Muhammad M; Elaimi, Aisha; Assidi, Mourad; Chaudhary, Adeel G; Abuzenadah, Adel M; Nedjadi, Taoufik; Ermiah, Eramah; Alkhayyat, Shadi S; Al-Qahtani, Mohammed H

    2015-12-01

    Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context.

  11. Investigation of telomerase activity and apoptosis on invasive ductal carcinoma of the breast using immunohistochemical and Western blot methods.

    PubMed

    Simsek, B C; Turk, B A; Ozen, F; Tuzcu, M; Kanter, M

    2015-08-01

    Invasive ductal carcinoma (IDC) comprises the largest group of breast cancers. This study aimed to investigate telomerase activity and apoptosis using immunohistochemical and Western blot methods. In total, 75 cases that had been diagnosed as IDC and 20 cases that had undergone a freezing procedure were included. The histological sections were stained with Bax, Bcl-2, hTERT and BNIP3. The ages of the patients, as well as their hormonal status and tumour sizes and grades were evaluated, as well as the staining characteristics of the antibodies in question. A decrease in Bcl-2 positivity and an increase in Bax positivity were found immunohistochemically with increasing tumour grades. The data obtained by western blot method showed that Bcl-2 was highest in grade 1 tumours although these results were not statistically significant. The relationship between estrogen and progesterone receptor positivity and Bcl-2 was statistically significant, suggesting there is hormonal control through apoptosis. BNIP3 was found to be decreased with increasing tumour grades. Similarly, BNIP3 was found to be having the lowest value in grade 3 tumours by western blot method. Furthermore, hTERT was found to be increased with increasing tumour grades. In the western blot method, hTERT increased nearly four-fold compared to the control. In addition, hTERT, which was seen in very high levels in tumours, may be a helpful cancer marker. Both hTERT and BNIP3 are important markers that can provide information about prognosis. Big improvements can be achieved in tumour progression control with new treatment modalities that stop telomerase activity and hypoxic cell death.

  12. High Levels of BCOX1 Expression Are Associated with Poor Prognosis in Patients with Invasive Ductal Carcinomas of the Breast

    PubMed Central

    Liu, Tong; Zhang, Xian-Yu; He, Xiao-Hui; Geng, Jing-Shu; Liu, Yang; Kong, De-Jia; Shi, Qing-Yu; Liu, Feng; Wei, Wei; Pang, Da

    2014-01-01

    This study was to examine the breast cancer-overexpressed gene 1 (BCOX1) expression in invasive ductal carcinomas (IDC) of the breast and its value in the prognosis of the disease. The levels of BCOX1 expression in 491 paired IDC and surrounding non-tumor breast tissues as well as 40 paired fresh specimens were evaluated by tissue microarray, immunohistochemistry and quantitative RT-PCR. The potential associations of high BCOX1 expression with clinicopathological variables and the overall survival of these patients were analyzed. The relative levels of BCOX1 mRNA transcripts in the IDC breast tissues were significantly higher than that in the corresponding non-tumor tissues (P = 0.005). The anti-BCOX1 was predominantly stained in the cytoplasm of breast tissue cells and the levels of BCOX1 expression in the majority of breast cancer tissues were obviously higher than that in the corresponding non-tumor breast tissues. High levels of BCOX1 expression were found in 59.5% (292/491) of breast cancer tissues. The high BCOX1 expression was significantly associated with high histological grade (P = 0.037), positive expression of human epidermal growth factor receptor 2 (HER2, P = 0.031) and triple negative breast cancer (P = 0.027). The high BCOX1 expression in breast cancers was significantly associated with a shorter overall survival of these patients (P = 0.023), particularly in patients with triple negative breast cancer (P = 0.005). Therefore, the high BCOX1 expression may serve as a novel marker of poor prognosis and a potential therapeutic target for patients with IDC of the breast. PMID:24489812

  13. Collision tumor: invasive ductal carcinoma in association with mucosa-associated lymphoid tissue (MALT) lymphoma in the same breast.

    PubMed

    Quilon, Joanne M; Gaskin, Thomas A; Ludwig, Arthur S; Alley, Catherine

    2006-02-01

    Synchronous occurrence of multiple neoplastic processes is uncommon and the relationship between breast cancer with lymphoproliferative diseases is unusual as well. Furthermore, breast involvement by malignant lymphoma is a rare event and primary breast mucosa-associated lymphoid tissue (MALT) lymphoma is even rarer. We report a patient with synchronous occurrence of malignant lymphoma of MALT type and ductal carcinoma of the breast, presenting as "collision tumor," invading each other and occurring as a single mass in the breast. Involvement of the sentinel lymph node by MALT lymphoma was demonstrated with no evidence of metastatic carcinoma. Staging bone marrow biopsy did not show involvement by malignant lymphoma or carcinoma. Our patient was treated with chemotherapy for the lymphoma. She also received radiotherapy and aromatase inhibitor as adjuvant therapy for the breast carcinoma.

  14. Id-1 overexpression in invasive ductal carcinoma cells is significantly associated with intratumoral microvessel density in ER-negative/node-positive breast cancer.

    PubMed

    Jang, Ki-Seok; Han, Hong Xiu; Paik, Seung Sam; Brown, Powel H; Kong, Gu

    2006-12-08

    The aim of this study is to investigate the possible role of inhibitor of DNA binding (Id-1) overexpression in human breast cancer. We examined Id-1 expression by immunohistochemistry in 263 human breast cancers, 15 in situ lesions and 248 invasive cancers to investigate the relationship between its expression and various clinicopathological factors. Id-1 expression was significantly higher in invasive ductal carcinoma than in in situ ductal carcinoma or other invasive cancer subtypes (P=0.029 and 0.006, respectively). We also examined the association between Id-1 expression and tumor angiogenesis by measuring microvessel densities (MVD). Regarding the endothelial cells of microvessels showed negative or very weak Id-1 expression, Id-1 overexpression was found to be significantly related to MVD (P=0.014). Furthermore, Id-1 overexpression was found to be significantly associated with higher MVD in the ER-negative and node-involved subgroups of breast cancer (P=0.040 and 0.046, respectively). These data indicate that Id-1 overexpression is significantly associated with tumor angiogenesis, especially in the ER-negative and node-positive subtypes of invasive breast cancer. Thus, Id-1 presents a possible therapeutic antitumor target molecule in ER-negative and node-positive breast cancer.

  15. Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database

    PubMed Central

    Li, Jun-Jing; Song, Chuan-Gui; Shao, Zhi-Ming

    2016-01-01

    Medullary breast carcinoma (MBC) is a unique histological subtype of breast cancer. Our study was designed to identify difference in characteristics and outcomes between MBC and invasive ductal carcinoma (IDC), and further confirm the prognostic factors of MBC. Utilizing Surveillance, Epidemiology, and End Results (SEER), we identified 84,764 eligible patients, including 309 MBC and 84,455 IDC. Compared with the IDC group, the MBC group was associated with younger age at diagnosis, higher grade, more advanced stage, larger tumor size, and higher proportion of triple-negative breast cancer (TNBC). Kaplan-Meier analysis and univariate Cox proportional hazard regression model showed that patients with IDC had significantly better breast cancer-specific survival (BCSS) compared to MBC, but they had similar overall survival (OS). However, MBC histology was no longer a surrogate for worse BCSS or OS after 1:1 matching by age, American Joint Committee on Cancer (AJCC) stage, grade and breast subtype. In addition, it was exposed that not married status, high grade, large tumor size, positive nodal status, the subtype of TNBC and no receipt of radiation therapy were significantly associated with poor BCSS and OS. In conclusion, MBC demonstrated more aggressive behavior but similar outcomes compared to IDC, which may be determined by prognostic factors such as breast subtype. These results not only confer deeper insight into MBC but contribute to individualized and tailored therapy, and thereby may improve clinical management and outcomes. PMID:27009810

  16. High Expression of Urokinase-Type Plasminogen Activator Is Associated with Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast

    PubMed Central

    Kim, Eun Young; Do, Sung-Im; Hyun, Keehoon; Park, Yong Lai; Kim, Dong-Hoon; Chae, Seoung Wan; Sohn, Jin Hee

    2016-01-01

    Purpose In the present study, we evaluated the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) by performing immunohistochemical staining to determine whether they were reliable prognostic markers in patients with breast cancer. Methods Demographic and clinicopathological parameters of 214 patients with invasive ductal carcinoma (IDC) and 80 patients with ductal carcinoma in situ (DCIS) who were diagnosed and treated from 2006 to 2010 were analyzed. Tissue microarray was constructed and immunohistochemical staining was performed for each specimen. Results Univariate analyses showed that age at diagnosis, history of hormone replacement therapy, radiation therapy, skin and chest wall invasion, Paget disease, lymphovascular invasion, estrogen receptor positivity, and triple-negative subtype were significantly associated with patient prognosis (p<0.005). Patients with DCIS showed higher PAI-1 expression than patients with IDC (82.5% and 36.2%, respectively; p=0.012). Lymph node metastasis was more frequent in patients with high uPA levels than in patients with low uPA levels (p=0.001). Conclusion Our results suggested that PAI-1 was involved in tumor progression in the early stages of breast cancer, such as DCIS. In addition, our results suggested that high uPA levels were associated with the lymph node metastasis of IDC. PMID:27382391

  17. Distribution of cancer stem cells in ductal invasive carcinoma of breast (review).

    PubMed

    Gudadze, M; Kankava, K; Mariamidze, A; Burkadze, G

    2013-09-01

    Despite advances in detection and treatment of breast cancer, mortality from this disease remains high. According to contemporary point of view the reason for this lies in fact, that in addition to intertumor heterogeneity, there is also a high degree of intratumor diversity in cancer cell population. For most cancers it is less clear which cells within the tumor clone possess tumor-initiating cell function. During studying oncogenesis and maligniяation processes a pool of cancer cells with stem characteristics - cancer stem cells (CSC) was identified. Indeed, the specifications of them let us conclude, that exactly these cells comprise the leading substrate for cancer initiation and self-renewal. Breast carcinomas have been reported to contain a subpopulation of CD44(+)/CD24(-)/low cancer cells, which are capable of generating tumors even when implanted in very low numbers. Exactly these cells are considered to be CSCs in different subtypes of breast cancer and cancers with CD44(+)/CD24(-)/low phenotype are confirmed to have a poor prognosis (but some controversies remain concerning this issue). The aim of the review was to assess the current literature published on the breast cancer stem cells. There are not so many studies, revealing the diversity of cancer stem cells in different types, different sizes and different grade of breast cancers. CSC distribution in breast cancer with lymph node involvement, metastasizing and chemoresistant cases, existence of circulating tumor cells in not studied precisely. So the concept of cancer stem cells in breast cancer is still a topic for discussions. This can bring light to a better understanding of the pathological process in breast cancer and ways to target it.

  18. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  19. Characteristics of invasive breast ductal carcinoma, NOS, diagnosed in a tertiary institution in the East Coast of Malaysia with a focus on tumor angiogenesis.

    PubMed

    Ch'ng, Ewe Seng; Tuan Sharif, Sharifah Emilia; Jaafar, Hasnan

    2012-01-01

    Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors. Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density. At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05). Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.

  20. Comparative evaluation of the erbB2 and hormone receptor status of neighboring invasive and in situ components of ductal carcinomas of the breast.

    PubMed

    Peres, Raquel Mary Rodrigues; Serra, Kátia Piton; Derchain, Sophie F M; Yoon, Jung Hyun; Pinto, Glauce Aperecida; Alvarenga, Marcelo; Soares, Fernando Augusto; Heinrich, Juliana K; da Cunha, Isabela Werneck; Vassallo, Jose; Sarian, Luís Otávio

    2009-01-01

    It remains unknown whether erbB2 expression and hormone receptor status predict the invasive potential of ductal carcinoma in situ (DCIS) of the breast. To examine erbB2 and estrogen/progesterone receptor (ER/PR) status in the precise areas where DCIS turns into invasive ductal carcinoma (IDC). Eighty-seven cases of breast malignancies harboring contiguous regions of DCIS and IDC were selected. Separate histological samples from the DCIS and the neighboring IDC were obtained using tissue microarrays. The erbB2 and ER/PR statuses were assessed using immunohistochemistry (erbB2 and ER/PR) and fluorescence in situ hybridization (FISH - only erbB2). The expression of erbB2 did not differ in the DCIS and IDC components of the breast tumors (p=0.35). There was good agreement in sample-by-sample comparisons of erbB2 (intraclass correlation coefficient [ICC]=0.78), PR (ICC=0.61) and ER (ICC=0.70) expression in the DCIS and IDC components. Our findings suggest that the expressions of erbB2 and ER/PR do not differ in the contiguous regions from DCIS to IDC.

  1. Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.

    PubMed

    Dabiri, Shahriar; Talebi, Amin; Shahryari, Jahanbanoo; Meymandi, Manzoumeh Shamsi; Safizadeh, Hossein

    2013-02-01

    This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue.  There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P < 0.001). We observed positive significant correlations between stromal myofibroblasts, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD ± DIN (P < 0.001). More myofibroblasts were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD ± DIN (P < 0.001).  MVC was inversely related to stromal myofibroblasts in invasive cancer (P < 0.001) and DCIS (P < 0.001), whereas there was a positive correlation in the stroma of FCD ± DIN (P = 0.002) and normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001).  Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts

  2. Ductal carcinoma in situ - update on risk assessment and management.

    PubMed

    Pang, Jia-Min B; Gorringe, Kylie L; Fox, Stephen B

    2016-01-01

    Ductal carcinoma in situ (DCIS) accounts for ~20-25% of breast cancers. While DCIS is not life-threatening, it may progress to invasive carcinoma over time, and treatment intended to prevent invasive progression may itself cause significant morbidity. Accurate risk assessment is therefore necessary to avoid over- or undertreatment of an individual patient. In this review we will outline the evidence for current management of DCIS, discuss approaches to DCIS risk assessment and challenges facing identification of novel DCIS biomarkers.

  3. Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database

    PubMed Central

    Lin, Pei-Yang; Zhang, Jie; Song, Chuan-Gui; Shao, Zhi-Ming

    2017-01-01

    Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients. PMID:28008158

  4. Clinical-Pathologic Features and Long-Term Outcomes of Tubular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma Treated With Breast Conservation Therapy

    SciTech Connect

    Liu, Gene-Fu F.; Yang Qifeng; Haffty, Bruce G.; Moran, Meena S.

    2009-12-01

    Purpose: To evaluate our institutional experience of treating tubular carcinoma of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery and radiation therapy, to compare clinical-pathologic features and long-term outcomes. Methods and Materials: A review of our institution's tumor registry from 1975 to 2007, followed by a central pathology review of available slides, yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with breast conservation therapy. Clinical-pathologic features and outcomes were analyzed by subtype to detect significant differences. Results: The median follow-up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs. 80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER-2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109) and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend toward improved breast cancer relapse-free survival for the TC cohort (95% vs. 87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral breast cancer relapse-free survival (all p values >0.05) between the cohorts. Conclusion: Our institutional experience suggests that TC, when compared with IDC, is associated with more favorable clinical-pathologic features and comparable, if not superior, outcomes after breast conservation therapy, suggesting the appropriateness of a conservative approach to this rare subtype.

  5. Effectiveness of Breast MRI and (18)F-FDG PET/CT for the Preoperative Staging of Invasive Lobular Carcinoma versus Ductal Carcinoma.

    PubMed

    Jung, Na Young; Kim, Sung Hoon; Kim, Sung Hun; Seo, Ye Young; Oh, Jin Kyoung; Choi, Hyun Su; You, Won Jong

    2015-03-01

    We evaluated the utility of magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the preoperative staging of invasive lobular carcinoma (ILC) of the breast and compared the results with those of invasive ductal carcinoma (IDC). The study included pathologically proven 32 ILCs and 73 IDCs. We compared clinical and histopathological characteristics and the diagnostic performances of MRI and (18)F-FDG PET/CT for the primary mass, additional ipsilateral and/or contralateral lesion(s), and axillary lymph node metastasis between the ILC and IDC groups. Primary ILCs were greater in size, but demonstrated lower maximum standardized uptake values than IDCs. All primary masses were detected on MRI. The detection rate for ILCs (75.0%) was lower than that for IDCs (83.6%) on (18)F-FDG PET/CT, but the difference was not significant. For additional ipsilateral lesion(s), the sensitivities and specificities of MRI were 87.5% and 58.3% for ILC and 100.0% and 66.7% for IDC, respectively; whereas the sensitivities and specificities of (18)F-FDG PET/CT were 0% and 91.7% for ILC and 37.5% and 94.7% for IDC, respectively. The sensitivity of (18)F-FDG PET/CT for ipsilateral lesion(s) was significantly lower in the ILC group than the IDC group. The sensitivity for ipsilateral lesion(s) was significantly higher with MRI; however, specificity was higher with (18)F-FDG PET/CT in both tumor groups. There was no significant difference in the diagnostic performance for additional contralateral lesion(s) or axillary lymph node metastasis on MRI or (18)F-FDG PET/CT for ILC versus IDC. The MRI and (18)F-FDG PET/CT detection rates for the primary cancer do not differ between the ILC and IDC groups. Although (18)F-FDG PET/CT demonstrates lower sensitivity for primary and additional ipsilateral lesions, it shows higher specificity for additional ipsilateral lesions, and could play a complementary role in the staging of

  6. Ductal Carcinoma in Situ: Clinical Perspective.

    PubMed

    Kühn, Thorsten

    2010-08-01

    Ductal carcinoma is situ (DCIS) is the fastest growing subtype of breast cancer, mainly because of improved screening activities. In contrast to invasive disease, DCIS is a local process with excellent survival rates. Current treatment strategies include surgery, radiotherapy (RT) and anti-hormonal treatment. The selection of an individual risk-adapted therapeutic approach remains controversial. This relates especially to the extent of surgery and the therapeutic index of adjuvant RT and tamoxifen. Several new trials have been published or updated recently that address important clinical issues. There is an urgent need to get more insight into the biological behaviour of different subtypes of DCIS, and develop more targeted and individualized treatment strategies. So far, surgery appears to be the most effective treatment modality. A morphology-based treatment model that allows complete resection of certain DCIS lesions without further adjuvant measures has not been evaluated prospectively and deserves further evaluation.

  7. Trends in Detection of Invasive Cancer and Ductal Carcinoma In Situ at Biennial Screening Mammography in Spain: A Retrospective Cohort Study

    PubMed Central

    Román, Marta; Rué, Montse; Sala, Maria; Ascunce, Nieves; Baré, Marisa; Baroja, Araceli; De la Vega, Mariola; Galcerán, Jaume; Natal, Carmen; Salas, Dolores; Sánchez-Jacob, Mercedes; Zubizarreta, Raquel; Castells, Xavier

    2013-01-01

    Background Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period. Methods Retrospective cohort study of 1,564,080 women aged 45–69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period. Results The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable. Conclusion Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002. PMID:24376649

  8. Trends in detection of invasive cancer and ductal carcinoma in situ at biennial screening mammography in Spain: a retrospective cohort study.

    PubMed

    Román, Marta; Rué, Montse; Sala, Maria; Ascunce, Nieves; Baré, Marisa; Baroja, Araceli; De la Vega, Mariola; Galcerán, Jaume; Natal, Carmen; Salas, Dolores; Sánchez-Jacob, Mercedes; Zubizarreta, Raquel; Castells, Xavier

    2013-01-01

    Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period. Retrospective cohort study of 1,564,080 women aged 45-69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period. The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable. Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002.

  9. Synchronous papillary thyroid carcinoma and breast ductal carcinoma

    PubMed Central

    Zhong, Jinjing; Lei, Jianyong; Jiang, Ke; Li, Zhihui; Gong, Rixiang; Zhu, Jingqiang

    2017-01-01

    Abstract Background: The incidences of both thyroid cancer and breast cancer have been rising in recent years; however, it is very rare to find a single person with both of these cancers. Only a few cases of synchronous thyroid and breast cancer have been published, and even fewer cases have been reported in older patients (>60 years). Case summary: The current study presents a case of synchronous papillary thyroid carcinoma and breast ductal carcinoma in an elderly patient. The patient first underwent a mastectomy and axillary lymphadenectomy in our department, followed by a total thyroidectomy and lymphadenectomy of the left lateral region of the neck 1 month later. Postoperative pathological examination identified invasive ductal carcinoma of the breast and papillary carcinoma of the thyroid. Over almost half a year of follow-up, the patient has exhibited no evidence of recurrence or metastasis, as demonstrated by careful ultrasound examinations. Herein, we not only report this case but also present a systematic review of the causes, diagnosis, and treatment of synchronous breast and thyroid cancer. Conclusion: Although synchronous primary tumors of the thyroid and breast are very rare, they remain a possibility; therefore, more attention should be paid to these cases. PMID:28207532

  10. Multicentric and contralateral invasive tumors identified with pre-op MRI in patients newly diagnosed with ductal carcinoma in situ of the breast.

    PubMed

    Hollingsworth, Alan B; Stough, Rebecca G

    2012-09-01

    Preoperative breast MRI in newly diagnosed cancer patients has several potential benefits. Improved survival for patients with invasive disease as the index lesion is unlikely to be one of these benefits, given what is known from variations in locoregional management in the historic conservation trials. However, this may not be the case for patients with ductal carcinoma in situ (DCIS), as the discovery of unsuspected invasive cancer located elsewhere from the biopsy-proven DCIS could result in decreased survival if left undetected and untreated. In support of this hypothesis, a previous observational study of a large cohort of DCIS patients revealed the development of invasive cancer to be the most common event after unilateral DCIS treatment, occurring in 3.9%, mostly in the opposite breast. These cancers appeared on mammography or clinical exam within a short time frame (median 2.9 years) and were associated with a diminution in survival. Given these second events occurring so soon after DCIS treatment, it must be considered that invasive cancers were present elsewhere, but mammographically occult, at the time of DCIS diagnosis. To examine this possibility, 288 consecutive patients with newly diagnosed DCIS underwent preoperative MRI, with the discovery of separate foci of invasive cancer, either multicentric or contralateral, occurring in 3.5% of patients, a similar incidence to the short-term observational study. These "elsewhere" invasive cancers are presented here with details of pathology such that both Stage I and Stage II disease can be seen as clinically significant, with the usual stage-based survival implications.

  11. The molecular underpinning of lobular histological growth pattern: a genome-wide transcriptomic analysis of invasive lobular carcinomas and grade- and molecular subtype-matched invasive ductal carcinomas of no special type.

    PubMed

    Weigelt, Britta; Geyer, Felipe C; Natrajan, Rachael; Lopez-Garcia, Maria A; Ahmad, Amar S; Savage, Kay; Kreike, Bas; Reis-Filho, Jorge S

    2010-01-01

    Invasive lobular carcinoma (ILC) is the most frequent special type of breast cancer. The majority of these tumours are of low histological grade, express hormone receptors, and lack HER2 expression. The pleomorphic variant of ILCs (PLCs) is characterized by atypical cells with pleomorphic nuclei and is reported to have an aggressive clinical behaviour. Expression profiling studies have demonstrated that classic ILCs preferentially display a luminal phenotype, whereas PLCs may be of luminal, HER2 or molecular apocrine subtypes. The aims of this study were two-fold: to determine the transcriptomic characteristics of lobular carcinomas and to define the genome-wide transcriptomic differences between classic ILCs and PLCs. To define the transcriptomic characteristics of ILCs, minimizing the impact of histological grade and molecular subtype on the analysis, we subjected a series of grade- and molecular subtype-matched ILCs and invasive ductal carcinomas (IDCs) to genome-wide gene expression profiling using oligonucleotide microarrays. Hierarchical clustering analysis demonstrated that ILCs formed a separate cluster and a supervised analysis revealed that 5.8% of the transcriptionally regulated genes were significantly differentially expressed in ILCs compared to grade- and molecular subtype-matched IDCs. ILCs displayed down-regulation of E-cadherin and of genes related to actin cytoskeleton remodelling, protein ubiquitin, DNA repair, cell adhesion, TGF-beta signalling; and up-regulation of transcription factors/immediate early genes, lipid/prostaglandin biosynthesis genes, and cell migration-associated genes. Supervised analysis of classic ILCs and PLCs demonstrated that less than 0.1% of genes were significantly differentially expressed between these tumour subtypes. Our results demonstrate that ILCs differ from grade- and molecular subtype-matched IDCs in the expression of genes related to cell adhesion, cell-to-cell signalling, and actin cytoskeleton signalling

  12. Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases.

    PubMed

    Tsuda, H; Takarabe, T; Hasegawa, F; Fukutomi, T; Hirohashi, S

    2000-02-01

    High-grade invasive ductal carcinomas (IDCs) of the breast with large, central acellular zones on their cut surfaces are usually associated with the myoepithelial immunophenotype of carcinoma cells, which includes the expression of S-100 protein, alpha-smooth muscle actin, and keratin 14. To clarify the clinical significance of these features of IDCs, the authors compared the incidence of the myoepithelial immunophenotype immunohistochemically, patient prognosis, and metastatic sites of the tumor between 20 high-grade IDCs with large, central acellular zones and 40 control high-grade IDCs without these zones. The myoepithelial immunophenotype was detected in 16 IDCs (80%) with large, central acellular zones but in only seven IDCs (18%) without. The risk ratio of metastasis, especially in the brain and lung, and death from cancer were significantly higher (p = 0.0096 and p = 0.030) for the 20 IDCs with large, central acellular zones than for those without by Cox's univariate analysis. Using Cox's multivariate analysis, large, central acellular zones in IDCs were an indicator of high risk of brain and lung metastases and of death by cancer independent of nodal status and tumor size. Examination of large, central acellular zones and myoepithelial immunophenotype in high-grade IDCs appears helpful in predicting patient prognosis and preferential metastatic sites of the tumors.

  13. Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report

    PubMed Central

    Matsuda, Ikuo; Watanabe, Takahiro; Enomoto, Yukie; Takatsuka, Yuichi; Miyoshi, Yasuo; Hirota, Seiichi

    2014-01-01

    Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer. PMID:25400790

  14. Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study

    PubMed Central

    Duffy, Stephen W; Dibden, Amanda; Michalopoulos, Dimitrios; Offman, Judith; Parmar, Dharmishta; Jenkins, Jacquie; Collins, Beverley; Robson, Tony; Scorfield, Suzanne; Green, Kathryn; Hall, Clare; Liao, Xiao-Hui; Ryan, Michael; Johnson, Fiona; Stevens, Guy; Kearins, Olive; Sellars, Sarah; Patnick, Julietta

    2016-01-01

    Summary Background The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen. Methods We obtained aggregate data for screen-detected cancers from 84 local screening units within 11 regional Quality Assurance Reference Centres in England, Wales, and Northern Ireland from the National Health Service Breast Screening Programme. Data for DCIS diagnoses were obtained for women aged 50–64 years who were invited to and attended mammographic breast screening from April 1, 2003, to March 31, 2007 (4 screening years). Patient-level data for interval cancer arising in the 36 months after each of these were analysed by Poisson regression with invasive interval cancer screen detection rate as the outcome variable; DCIS detection frequencies were fitted first as a continuous and then as a categorical variable. We repeated this analysis after adjustment with both small size and high-grade invasive screen-detected cancers. Findings We analysed data for 5 243 658 women and on interval cancers occurring in the 36 months after the relevant screen. The average frequency of DCIS detected at screening was 1·60 per 1000 women screened (median 1·50 [unit range 1·54–3·56] per 1000 women). There was a significant negative association of screen-detected DCIS cases with the rate of invasive interval cancers (Poisson regression coefficient −0·084 [95% CI −0·13 to −0·03]; p=0·002). 90% of units had a DCIS detection frequency within the range of 1·00 to 2·22 per 1000 women; in these units, for every three screen-detected cases of DCIS, there was one fewer invasive interval cancer in the next 3 years. This association remained after

  15. [A case of metachronous invasive ductal carcinoma concomitant with intraductal papillary-mucinous neoplasm (IPMN) of the pancreas, which could not be detected in contrast-enhanced CT scan performed 3 months ago].

    PubMed

    Hasebe, Osamu; Ochi, Yasuhide; Hara, Etsuo; Suzawa, Kenichi; Seki, Ayako; Nagaya, Tadanobu; Tatai, Toshiharu; Jimbo, Yoko; Hosaka, Noriko

    2011-09-01

    A 61-year-old man had been followed up in another hospital under diagnosis of branch duct type IPMN for 4 years. Contrast-enhanced CT scan for regular check performed 3 months ago revealed no increase of IPMN and no pancreatic tumor. However, he complained of back pain after that, MRI was performed. It revealed a solid tumor in size of 25mm diameter at the head of pancreas. The tumor was apparent from IPMN in several imaging modalities. Pancreatoduodenectomy was performed under diagnosis of invasive ductal carcinoma concomitant with IPMN. Post-operative pathological findings revealed IPMN was adenoma with mild atypia, and solid tumor was diagnosed invasive ductal carcinoma with solitary minute liver metastasis.

  16. Sclerosing ductal carcinoma of the clitoris with microcystic adnexal carcinoma-like features.

    PubMed

    DuPont, Nefertiti C; Mabuchi, Seiji; Ries, Savita; Berman, Michael L

    2009-03-01

    Primary clitoral malignancies are rare and most are invasive squamous cell carcinomas. Microcystic adnexal carcinoma (MAC) is an indolent, rare dermatologic carcinoma that typically affects the head and neck region. A 23-year-old nulligravid Hispanic female presented with a 9-month history of an enlarging periclitoral mass. After surgical resection, the mass was diagnosed as a MAC. MAC is a cutaneous carcinoma rarely found on the vulva. It is a slow growing but locally aggressive carcinoma that is best treated with surgical resection. Sclerosing ductal carcinomas may have MAC-like features, and the diagnosis and management of one case is provided here.

  17. Physiological COX-2 expression in breast epithelium associates with COX-2 levels in ductal carcinoma in situ and invasive breast cancer in young women.

    PubMed

    Fornetti, Jaime; Jindal, Sonali; Middleton, Kara A; Borges, Virginia F; Schedin, Pepper

    2014-04-01

    Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population.

  18. Physiological COX-2 Expression in Breast Epithelium Associates with COX-2 Levels in Ductal Carcinoma in Situ and Invasive Breast Cancer in Young Women

    PubMed Central

    Fornetti, Jaime; Jindal, Sonali; Middleton, Kara A.; Borges, Virginia F.; Schedin, Pepper

    2015-01-01

    Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population. PMID:24518566

  19. Ductal eccrine carcinoma of the axilla: a diagnostic pitfall*

    PubMed Central

    de Brito, Maria Helena Toda Sanches; Dionísio, Cecília Silva Nunes de Moura; Ferreira, Joana Cintia Monteiro; Rosa, Maria Joaninha Madalena de Palma Mendonça da Costa; Cunha, Fernando Petrucci Bernardo e; Garcia, Maria Manuela Antunes Pecegueiro da Silva

    2017-01-01

    Ductal eccrine carcinoma (DEC) is a rare sweat gland carcinoma with ductular differentiation. Clinically, it is characterized by a slowly growing, hardened plaque or nodule predominantly located on the head and neck. Histologically, DEC shares similar features to invasive breast carcinoma, thus causing great diagnostic challenges. We report a 69-year-old woman who presented with a hardened plaque on the axilla. A skin biopsy was performed and metastatic invasive breast carcinoma could not be ruled out. Complete excision and further workup were subsequently conducted, leading to the diagnosis of estrogen receptor positive DEC with associated axillary lymph node metastases. The patient received adjuvant radiotherapy to the left axilla and was started on oral letrozole. She is disease-free 14 months after initial diagnosis. PMID:28538887

  20. Appraisal of the technologies and review of the genomic landscape of ductal carcinoma in situ of the breast.

    PubMed

    Pang, Jia-Min B; Gorringe, Kylie L; Wong, Stephen Q; Dobrovic, Alexander; Campbell, Ian G; Fox, Stephen B

    2015-06-16

    Ductal carcinoma in situ is a biologically diverse entity. Whereas some lesions are cured by local surgical excision, others recur as in situ disease or progress to invasive carcinoma with subsequent potential for metastatic spread. Reliable prognostic biomarkers are therefore desirable for appropriate clinical management but remain elusive. In common with invasive breast cancer, ductal carcinoma in situ exhibits many genomic changes, predominantly copy number alterations. Although studies have revealed the genomic heterogeneity within individual ductal carcinoma in situ lesions and the association of certain copy number alterations with nuclear grade, none of the genomic changes defined so far is consistently associated with invasive transformation or recurrence risk in pure ductal carcinoma in situ. This article will review the current landscape of genomic alterations in ductal carcinoma in situ and their potential as prognostic biomarkers together with the technologies used to define these.

  1. Clinical significance of Maspin promoter methylation and loss of its protein expression in invasive ductal breast carcinoma: correlation with VEGF-A and MTA1 expression.

    PubMed

    Sharma, Gayatri; Mirza, Sameer; Parshad, Rajinder; Srivastava, Anurag; Gupta, Siddartha Datta; Pandya, Pranav; Ralhan, Ranju

    2011-02-01

    Maspin is a serine protease inhibitor with tumor-suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Previous studies indicate that the loss of Maspin expression is closely linked to aberrant methylation of the Maspin promoter. We examined the promoter methylation status of Maspin in tumor and corresponding serum of breast cancer patients. In addition, protein expression of this gene was also assessed to determine possible correlation between promoter hypermethylation and gene silencing. Further, we investigated the correlation of Maspin expression with vascular endothelial growth factor (VEGF-A) and MTA1 expression. Maspin methylation was analyzed by methylation-specific PCR in 100 invasive ductal breast carcinoma patients' tumors and circulating DNA in a prospective study. Promoter hypermethylation was correlated with expression of the encoded protein in tumors by immunohistochemistry. Significant correlation was observed between promoter hypermethylation of Maspin (r = +0.88; p ≤ 0.0001) in tumors and paired sera. Significant association was found between Maspin promoter hypermethylation and loss of its protein expression (p = 0.01, OR = 3.1, 95% CI = 1.3-7.4). The expression of VEGF-A and MTA1 was lower in tumors with high Maspin expression compared to tumors with loss of Maspin expression. Our results indicate that aberrant promoter methylation is associated with loss of Maspin immunoreactivity in breast cancer tissues. Further, loss of Maspin expression is significantly correlated with increased expression of VEGF-A and MTA1.

  2. Reliability of (18)F-FDG PET Metabolic Parameters Derived Using Simultaneous PET/MRI and Correlation With Prognostic Factors of Invasive Ductal Carcinoma: A Feasibility Study.

    PubMed

    Jena, Amarnath; Taneja, Sangeeta; Singh, Aru; Negi, Pradeep; Sarin, Ramesh; Das, Pratap K; Singhal, Manish

    2017-09-01

    The objective of our study was to correlate semiquantitative PET parameters-standardized uptake value (SUV) and total lesion glycolysis (TLG)-derived in simultaneous PET/MRI using MRI-based attenuation correction with clinical and histopathologic prognostic factors in patients with breast cancer. Eighty-two invasive ductal carcinomas in 69 women were included in the study. All the subjects underwent whole-body (WB) PET/MRI (supine WB mode) and dedicated PET/MRI of the breast (prone breast imaging mode) for staging on a simultaneous PET/MRI system. The SUV and TLG values were calculated from (18)F-FDG PET data using MRI-based attenuation correction (2-point Dixon sequence for tissue segmentation). Relationships between SUV and TLG values and clinical and histopathologic parameters (i.e., tumor size, tumor grade, Ki-67 status, and hormonal receptor expression status) were evaluated using Spearman correlation coefficient analysis. A significant correlation was observed between mean SUV (SUVmean) and maximum SUV (SUVmax) values derived with WB PET and regional PET of the breasts performed simultaneously with MRI (r = 0.88 and 0.89, respectively). A significant difference (p < 0.05) was observed in SUVmean, SUVmax, and TLG values between the grades and molecular subtypes of breast cancer. High SUVmean, SUVmax, and TLG values were found to correlate with larger tumor size (p < 0.01), higher proliferation index (p < 0.05), higher grade (p < 0.01), and triple-negative hormonal receptor status (p < 0.01, p < 0.05). Semiquantitative FDG parameters derived with MRI-based attenuation correction in simultaneous PET/MRI are reliable and correlate with clinicopathologic features such as grade as well as subtype and thus could be used in the prognostication of breast cancer.

  3. Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma.

    PubMed

    Hartog, Hermien; Horlings, Hugo M; van der Vegt, Bert; Kreike, Bas; Ajouaou, Abderrahim; van de Vijver, Marc J; Marike Boezen, H; de Bock, Geertruida H; van der Graaf, Winette T A; Wesseling, Jelle

    2011-10-01

    The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast carcinoma (IDC), the most common type of breast cancer. Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary IDC. Associations between IGF1R expression with clinicopathological parameters, disease free survival (DFS) and breast cancer specific survival (BCSS) were evaluated by multivariate analyses focusing on ER-positive and triple negative IDC (TN-IDC). To enlarge the TN-IDCs cohort, we analyzed a combined dataset of 51 TN-IDC tumors from our series with 64 TN-IDCs with similar clinicopathological parameters. Patients with tumors expressing cytoplasmic IGF1R have a longer DFS and BCSS (DFS: HR 0.46, 95% CI 0.27-0.49, P = 0.005, BCSS: HR 0.38, 95% CI 0.19-0.74, P = 0.005). This effect was most prominent in ER-positive tumors. However, in a combined series of 105 TN-IDCs cytoplasmic IGF1R expression was associated with a shorter DFS (HR = 2.29, 95% CI 1.08-4.84, P = 0.03), also when combined in a multivariate model, including well-known prognostic factors (HR 2.06; 95% CI 0.95-4.47; P = 0.07). IGF1R expression in ER-positive IDC is strongly related to a favorable DFS and BCSS, but to a shorter DFS in TN-IDC tumors. This divergent effect of IGF1R expression in subgroups of IDC may affect selection of patients for IGF1R targeted therapy.

  4. Serum Soluble CD14 Is a Potential Prognostic Indicator of Recurrence of Human Breast Invasive Ductal Carcinoma with Her2-Enriched Subtype

    PubMed Central

    He, Weifeng; Tong, Yifan; Wang, Ying; Liu, Jingjing; Luo, Gaoxing; Wu, Jun; Zhang, Jin

    2013-01-01

    In clinical practice, breast cancers with lymph node positive, ER/PR-negative and overexpressed human epidermal growth factor receptor 2 (LN+ER/PR-Her2+) have high risk of recurrence, but the effective biomarkers of prognostic for this type tumor are still lacking. Since breast cancers with LN+ER/PR-Her2+ is at higher risk of recurrence than those with LN-ER/PR+Her2-. The differential proteins between those two groups could be related to the risk of recurrence. Herein, we report that serum soluble CD14 (sCD14) was revealed as the stable differential protein between LN+ER/PR-Her2+ (n=50) and LN-ER/PR+Her2- (n=50) breast cancer patients by proteomics analysis. To validate sCD14 as a biomarker for predicting recurrence of breast cancer, 90 breast cancer patients with LN+ER/PR-Her2+ and 93 patients with LN-ER/PR+Her2- were recruited. The patients with higher level of serum sCD14 at primary surgery showed to be at significantly lower risk of relapse in 3 years follow-up than those with lower level of serum sCD14 at primary surgery. The levels of serum sCD14 at primary surgery were significantly correlated to the risk of 3-year recurrence of LN+ER/PR-Her2+ breast cancer and the corresponding AUC of the ROC curve was 0.833 (95% CI, and 0.742 to 0.920). Therefore, we surmise that serum sCD14 could be a potential biomarker for predicting the prognosis of breast invasive ductal carcinoma with LN+ER/PR-Her2+. PMID:24086515

  5. Histogram analysis of apparent diffusion coefficient at 3.0t: Correlation with prognostic factors and subtypes of invasive ductal carcinoma.

    PubMed

    Kim, Eun Jeong; Kim, Sung Hun; Park, Ga Eun; Kang, Bong Joo; Song, Byung Joo; Kim, Yun Ju; Lee, Dongeon; Ahn, Hyunsoo; Kim, Inah; Son, Yo Han; Grimm, Robert

    2015-12-01

    To evaluate apparent diffusion coefficient (ADC) histogram parameters that show correlations with prognostic factors and subtypes of breast cancer. At 3.0T, various ADC histogram parameters were calculated including the entire tumor volume in 173 invasive ductal carcinomas: the minimum, 10th percentile, mean, median, 90th percentile, and maximum. ADC parameters were correlated with prognostic factors and subtype. The mean ADCmedian value was significantly higher in the group with lymph node metastasis, HER2 positivity, and a Ki-67 value <14% than in the group with negativity for lymph node metastasis, HER2 negativity, and a Ki-67 value ≥14% (0.907, 0.978, and 0.941 vs. 0.735, 0.778, and 0.761 × 10(-3) mm(2) /s, respectively) (P < 0.01). There was no significant correlation between ADCmedian and tumor size, histologic grade, estrogen receptor expression, and progesterone receptor expression (P = 0.272, 0.113, 0.261, and 0.181, respectively). For most ADC parameters except for ADCmin , the mean of variable ADC parameters of HER2-positive, luminal A, luminal B-HER2(+), triple-negative, and luminal B-HER2(-) diseases were arranged in descending order (1.175, 0.936, 0.863, 0.811, and 0.665 × 10(-3) mm(2) /s in ADCmedian , respectively) with statistical significant difference (P < 0.001). In multivariate analysis, histologic grade, the Ki-67 index, and HER2 expression were statistically significant explanatory prognostic factors for ADCmedian and the Ki-67 index had the most robust effects on ADC parameters (standardized coefficient = -0.317). Various ADC parameters were correlated with prognostic factors and subtype, except for ADCmin . HER2 positivity showed high ADC values and high Ki-67 index revealed low ADC values. © 2015 Wiley Periodicals, Inc.

  6. Strategies for the treatment of invasive ductal carcinoma of the pancreas and how to achieve zero mortality for pancreaticoduodenectomy.

    PubMed

    Kimura, Wataru

    2008-01-01

    Although various therapeutic modalities are available for carcinoma of the pancreas, "curative resection" is the most important. Thus, the aim of surgery for carcinoma of the pancreas is local complete resection of the carcinoma. Carcinoma of the head of the pancreas invades through the pancreatic parenchyma, following the arteries, veins, and especially nerves between the parenchyma and fusion fascia, and then spreads horizontally toward the superior mesenteric artery or celiac axis. We suggest techniques for resection of the extrapancreatic nerve plexus in the head of the pancreas during a Whipple procedure for carcinoma of the pancreas, from the perspective of surgical anatomy and pathology, to achieve "curative resection". We suggest that: (1) en-bloc resection of the right side of the superior nerve plexus and the first and second nerve of the pancreatic head should be performed. With this technique, it is possible to avoid cutting these nerves. It is easy to perform this procedure, as follows. First, the superior mesenteric artery and vein are encircled with tape. Next, the superior mesenteric artery should be moved to the right side of the superior mesenteric vein under this vein. In addition, (2) the entire cut end of the nerve plexus should be investigated during the operation, using frozen specimens, and confirmed to be negative for cancer. If the cut end is positive for cancer, additional resection of the nerve plexus should be performed to achieve curative resection. It is impossible to completely determine whether the cut end of the nerve plexus is positive or negative for carcinoma after surgery, because the cut end is long and some specimens are deformed by formalin fixation; thus, it is difficult to identify the true surgical cut end. With regard to reconstruction, we perform a modified Child method with pancreaticojejunostomy (end-to-side), choledochoduodenostomy (also end-to-side), and gastrojejunostomy with Braun's anastomosis. The greater

  7. US appearance of ductal carcinoma in situ.

    PubMed

    Wang, Lilian C; Sullivan, Megan; Du, Hongyan; Feldman, Marina I; Mendelson, Ellen B

    2013-01-01

    Ductal carcinoma in situ (DCIS) is a noninvasive cancer that accounts for 25% of all breast cancers diagnosed in the United States. DCIS is a heterogeneous disease process with varied clinical manifestations and a broad spectrum of imaging findings. With advances in technology, the ability to detect early-stage cancers has improved, and understanding the role of ultrasonography (US) in the multimodality era of detection and diagnosis is paramount. When calcifications are identified at mammography, US can be performed to evaluate for an invasive component and to allow possible US-guided biopsy. Use of high-frequency transducers, spectral compounding, and speckle reduction algorithms can aid in the detection of calcifications. Calcified DCIS most commonly manifests as echogenic foci located within a mass or duct, associated with internal microlobulations, or distributed in a branch pattern. Noncalcified DCIS, which is more often identified in symptomatic patients, may manifest as a hypoechoic mass with microlobulated margins and no posterior acoustic features, or it may have a "pseudomicrocystic" appearance. Harmonic imaging and coronal reconstruction may improve detection of noncalcified DCIS. The appearance of DCIS at "second-look" US can be subtle and may warrant a lower threshold for detection, given a higher pretest probability of malignancy. US features are nonspecific, and careful correlation with respect to lesion location, size, shape, and depth is needed. The presence of internal vascularity can help increase the positive predictive value of US in this setting. US is a useful adjunct to mammography and magnetic resonance imaging, and recognizing the US appearance of DCIS will aid in the detection and diagnosis of this disease entity.

  8. Nuclear grade plus proliferation grading system for invasive ductal carcinoma of the breast: validation in a tertiary referral hospital cohort.

    PubMed

    Papadimitriou, Maria; Kaptanis, Sarantos; Polymeropoulos, Evangelos; Mitsopoulos, Grigorios; Stogiannis, Dimitris; Caroni, Chrys; Vaiopoulos, George; Panayiotides, Joannis G; Karakitsos, Petros

    2015-12-01

    For patients with invasive breast cancer, management decisions are informed by tumor grade according to the Nottingham Grading System (NGS), either on its own or as part of the Nottingham Prognostic Index (NPI). A system retaining the nuclear grade element but substituting the two subjective components, mitosis count and tubule formation, of the NGS with a proliferation index based on Ki-67 (MIB-1) has been proposed (nuclear grade plus proliferation [N+P] grading). We validated the prognostic value of this grading system on a population of 322 women. N+P grading resulted in more grade I tumors (47.9% vs 4.5%) and fewer grade II (32% vs 51.5%) and grade III (20.1% vs 44%) tumors compared with NGS. The NPI calculated based on N+P grade had a similar association with survival (P < .001; odds ratio, 1.729) as the NPI calculated on the basis of the NGS grade (P < .001; odds ratio, 1.668). The N+P system seems equivalent to the NGS system. Copyright© by the American Society for Clinical Pathology.

  9. Myoepithelial Cell Differentiation Markers in Ductal Carcinoma in Situ Progression

    PubMed Central

    Russell, Tanya D.; Jindal, Sonali; Agunbiade, Samiat; Gao, Dexiang; Troxell, Megan; Borges, Virginia F.; Schedin, Pepper

    2016-01-01

    We describe a preclinical model that investigates progression of early-stage ductal carcinoma in situ (DCIS) and report that compromised myoepithelial cell differentiation occurs before transition to invasive disease. Human breast cancer MCF10DCIS.com cells were delivered into the mouse mammary teat by intraductal injection in the absence of surgical manipulations and accompanying wound-healing confounders. DCIS-like lesions developed throughout the mammary ducts with full representation of human DCIS histologic patterns. Tumor cells were incorporated into the normal mammary epithelium, developed ductal intraepithelial neoplasia and DCIS, and progressed to invasive carcinoma, suggesting the model provides a rigorous approach to study early stages of breast cancer progression. Mammary glands were evaluated for myoepithelium integrity with immunohistochemical assays. Progressive loss of the myoepithelial cell differentiation markers p63, calponin, and α-smooth muscle actin was observed in the mouse myoepithelium surrounding DCIS-involved ducts. p63 loss was an early indicator, calponin loss intermediate, and α-smooth muscle actin a later indicator of compromised myoepithelium. Loss of myoepithelial calponin was specifically associated with gain of the basal marker p63 in adjacent tumor cells. In single time point biopsies obtained from 16 women diagnosed with pure DCIS, a similar loss in myoepithelial cell markers was observed. These results suggest that further research is warranted into the role of myoepithelial cell p63 and calponin expression on DCIS progression to invasive disease. PMID:26343330

  10. Treatment of low-risk ductal carcinoma in situ: is nothing better than something?

    PubMed

    Benson, John R; Jatoi, Ismail; Toi, Masakazu

    2016-10-01

    The heterogeneous nature of ductal carcinoma in situ has been emphasised by data for breast-cancer screening that show substantial increases in the detection of early-stage non-invasive breast cancer but no noteworthy change in the incidence of invasive and distant metastatic disease. Indolent non-progressive forms of ductal carcinoma in situ are managed according to similar surgical strategies as high-risk disease, with extent of resection dictated by radiological and pathological estimates of tumour dimensions. Although adjuvant treatments might be withheld for low-risk lesions, surgical treatments incur potential morbidity, especially when mastectomy and breast reconstruction are done for widespread low-grade or intermediate-grade ductal carcinoma in situ. Low rates of deaths from breast cancer coupled with overdiagnosis within screening programmes have prompted a fundamental rethink of approaches to the management of both low-risk and high-risk ductal carcinoma in situ. Changes include active surveillance for low-risk lesions and a watchful waiting policy with intervention when invasive local recurrence after breast-conserving surgery is detected. Prediction of ipsilateral invasive recurrence is likely to be improved by integration of molecular biomarkers with conventional histopathological parameters. Moreover, further genetic interrogation of ductal carcinoma in situ might lead to a reclassification of some low-grade lesions as non-cancerous entities.

  11. Protein expression and methylation of MGMT, a DNA repair gene and their correlation with clinicopathological parameters in invasive ductal carcinoma of the breast.

    PubMed

    Asiaf, Asia; Ahmad, Shiekh Tanveer; Malik, Ajaz Ahmad; Aziz, Shiekh Aejaz; Rasool, Zubaida; Masood, Akbar; Zargar, Mohammad Afzal

    2015-08-01

    Epigenetic mechanisms such as DNA methylation are being increasingly recognized to play an important role in cancer and may serve as a cancer biomarker. The aim of this study was to evaluate the promoter methylation status of MGMT (O6-methylguanine-DNA methyltransferase) and a possible correlation with the expression of MGMT and standard clinicopathological parameters in invasive ductal breast carcinoma patients (IDC) of Kashmir. Methylation-specific PCR was carried out to investigate the promoter methylation status of MGMT in breast tumors paired with the corresponding normal tissue samples from 128 breast cancer patients. The effect of promoter methylation on protein expression in the primary breast cancer and adjacent normal tissues was evaluated by immunohistochemistry (n = 128) and western blotting (n = 30). The frequency of tumor hypermethylation was 39.8 % and a significant difference in methylation frequency among breast tumors were found (p < 0.001) when compared with the corresponding normal tissue. Immunohistochemical analysis showed no detectable expression of MGMT in 68/128 (53.1 %) tumors. MGMT promoter methylation mediated gene silencing was associated with loss of its protein expression (rs = -0.285, p = 0.001, OR = 3.38, 95 % CI = 1.59-7.17). A significant correlation was seen between loss of MGMT and lymph node involvement (p = 0.030), tumor grade (p < 0.0001), loss of estrogen receptors (ER; p = 0.021) and progesterone receptors (PR) (p = 0.016). Also, MGMT methylation was found to be associated with tumor grade (p = 0.011), tumor stage (p = 0.009), and loss of ER (p = 0.003) and PR receptors (p = 0.009). To our knowledge, our findings, for the first time, in Kashmiri population, indicate that MGMT is aberrantly methylated in breast cancer and promoter hypermethylation could be attributed to silencing of MGMT gene expression in breast cancer. Our data suggests that MGMT promoter

  12. The Role of High-Resolution Magic Angle Spinning 1H Nuclear Magnetic Resonance Spectroscopy for Predicting the Invasive Component in Patients with Ductal Carcinoma In Situ Diagnosed on Preoperative Biopsy

    PubMed Central

    Chae, Eun Young; Kim, Suhkmann; Baek, Hyeon-Man; Yoon, Dahye; Kim, Siwon; Shim, Ye Eun; Kim, Hak Hee; Cha, Joo Hee; Choi, Woo Jung; Lee, Jeong Hyun; Shin, Ji Hoon; Lee, Hee Jin; Gong, Gyungyub

    2016-01-01

    The purpose of this study was to evaluate the role of high-resolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy in patients with ductal carcinoma in situ (DCIS) diagnosed on preoperative biopsy. We investigated whether the metabolic profiling of tissue samples using HR-MAS 1H NMR spectroscopy could be used to distinguish between DCIS lesions with or without an invasive component. Our institutional review board approved this combined retrospective and prospective study. Tissue samples were collected from 30 patients with pure DCIS and from 30 with DCIS accompanying invasive carcinoma. All patients were diagnosed with DCIS by preoperative core-needle biopsy and underwent surgical resection. The metabolic profiling of tissue samples was performed by HR-MAS 1H NMR spectroscopy. All observable metabolite signals were identified and quantified in all tissue samples. Metabolite intensity normalized by total spectral intensities was compared according to the tumor type using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). By univariate analysis, the metabolite concentrations of choline-containing compounds obtained with HR-MAS 1H NMR spectroscopy did not differ significantly between the pure DCIS and DCIS accompanying invasive carcinoma groups. However, the GPC/PC ratio was higher in the pure DCIS group than in the DCIS accompanying invasive carcinoma group (p = 0.004, Bonferroni-corrected p = 0.064), as well as the concentration of myo-inositol and succinate. By multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles could clearly discriminate between pure DCIS and DCIS accompanying invasive carcinoma. Our preliminary results suggest that HR-MAS MR metabolomics on breast tissue may be able to distinguish between DCIS lesions with or without an invasive component. PMID:27560937

  13. Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

    PubMed Central

    Mahoney, M. Ellen; Gordon, Eva J.; Rao, Jian Yu; Jin, Yusheng; Hylton, Nola; Love, Susan M.

    2014-01-01

    Many women with ductal carcinoma in situ (DCIS) are treated with extensive surgery, radiation, and hormone therapy due to the inability to monitor the disease and to determine which cases will progress to invasive cancer. We assessed the safety and feasibility of administering chemotherapy directly into DCIS-containing ducts in 13 women before definitive surgery. The treatment was safe, feasible, and well tolerated, supporting further development of this strategy for management of DCIS. Introduction Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. Patients and Methods Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. Results Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. Conclusions Intraductal therapy offers

  14. Axillary node dissection in ductal carcinoma in situ.

    PubMed

    Parker, R G; Berkbigler, D; Rees, K; Leung, K M; Legorreta, A P

    1998-04-01

    Intraductal carcinoma of the breast has become a well-defined entity that has been more frequently diagnosed since the introduction of mammography. For many years, the usual treatment has been mastectomy, often with axillary lymph node dissection. Concurrent with documentation that breast conservation treatment has been effective for many invasive breast cancers, such treatment has been introduced for noninvasive breast cancers (ductal carcinoma in situ and lobular cancer in situ). However, there is no basis for axillary dissection because tumor cells are contained by the basement membrane and should not metastasize. In this study, 107 axillary dissections were carried out, with an average of 20 nodes identified, and a single metastasis was identified.

  15. [ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma].

    PubMed

    Peres, Raquel Mary Rodrigues; Derchain, Sophie Françoise Mauricette; Heinrich, Juliana Karina Ruiz; Serra, Kátia Piton; Pinto, Glauce Aparecida; Soares, Fernando Augusto; Sarian, Luís Otávio Zanatta

    2009-09-01

    to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5% (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.

  16. Ductal carcinoma in situ of breast: detection and treatment pattern in Hong Kong.

    PubMed

    Yau, T K; Chan, A; Cheung, P Sy

    2017-02-01

    The treatment of ductal carcinoma in situ has been widely reported in the western and other Asian countries, but the relevant data in Hong Kong are relatively limited. This study aimed to evaluate the latest detection and treatment pattern for ductal carcinoma in situ in Hong Kong so as to guide planning of future service provision. This was a retrospective case series study. A total of 573 patients who registered with the Hong Kong Breast Cancer Registry, and were diagnosed and treated in Hong Kong from January 2001 to December 2011 were reviewed. Compared with invasive breast cancer patients, patients with ductal carcinoma in situ were younger (median, 48.6 vs 50.3 years; P<0.001), had a higher education level (P<0.001), had a higher total monthly family income (P<0.001), and more common breast-screening habits (P<0.001). Significantly more patients with ductal carcinoma in situ underwent breast-conserving surgery than their invasive cancer counterparts (55.8% vs 36.7%; P<0.001). The percentage of screen-detected ductal carcinoma in situ was relatively lower than that reported in other studies, but was still much higher than that in invasive breast cancer patients (29.0% vs 4.7%; P<0.001). Screen-detected patients with ductal carcinoma in situ tended to choose a private hospital instead of a public hospital for treatment (P=0.05) and to undergo breast-conserving surgery (P=0.02). With a median follow-up of 3 years, the crude local recurrence rate after mastectomy and breast-conserving surgery was 0.4% and 3.3%, respectively; 44% of recurrent tumours had developed invasive components. No regional recurrence, distant recurrence, or cancer-related deaths were recorded. In the absence of a population-based breast screening programme in Hong Kong, ductal carcinoma in situ is more frequently found in the higher social classes and managed in the private sector. The clinical outcome of ductal carcinoma in situ is excellent and more than half of the patients can be

  17. Immunohistochemistry applied to the differential diagnosis between ductal and lobular carcinoma of the breast.

    PubMed

    de Deus Moura, Rafael; Wludarski, Sheila C L; Carvalho, Filomena M; Bacchi, Carlos E

    2013-01-01

    The distinction between classic lobular and ductal carcinoma, both in situ and invasive, has important therapeutic and management implications. Most ductal and lobular carcinomas are distinguished readily on hematoxylin-eosin-stained sections because of distinct histomorphologic features. In cases with ambiguous morphologic features, however, categorization in one or another type can be a challenge. Several immunohistochemical markers, including epithelial cadherin, p120, β-catenin, and low-molecular-weight and high-molecular-weight cytokeratins among others, have been introduced to help better discriminate between lobular neoplasia and ductal carcinoma. In this critical review of the literature, we comment about the usefulness and the limitations of these markers to improve the accuracy in the differential diagnosis of breast pathology.

  18. Management of ductal carcinoma in situ of the breast.

    PubMed

    Carty, N J; Carter, C; Royle, G T; Johnson, C D

    1995-05-01

    The advent of mammographic breast screening has increased the detection of ductal carcinoma in situ (DCIS), which now accounts for 15-20% of all breast cancer. While symptomatic DCIS has been treated satisfactorily by mastectomy, this may be an overtreatment of smaller screen-detected lesions. Although local excision, with or without radiotherapy, is associated with a significant risk of local recurrence of DCIS or invasive cancer, salvage surgery is usually successful. The long-term breast-specific mortality rate of treatment by mastectomy and local excision are similar. Whereas mastectomy is still appropriate for women with lesions > 30 mm in diameter or centrally placed and for those women who demand the best possible disease-free survival, local surgery should otherwise be considered.

  19. Relation between radiographic BI-RADS scores and triple negativity in patients with ductal carcinomas.

    PubMed

    Oktay, Murat; Oktay, Nilay Aydın; Besir, Fahri Halit; Buyukkaya, Ramazan; Erdem, Havva; Onal, Binnur; Ozaydın, Ismet; Yazıcı, Burhan

    2014-01-01

    The aim of this study was to investigate association of radiographic (BI-RADS 4 and 5) results and prognostic factors of invasive ductal carcinomas with their histopathological subtypes. A total of 103 patients histopathologically diagnosed with invasive ductal carcinoma of breast with in last five years period were enrolled. Of them, 69 patients who had radiological reports in were included from registry of Radiology Department; Duzce University Training and Research Hospital archives. BI-RADS scores (4 and 5) of radiological reports and subtypes of ductal carcinoma were compared. Of 69 cases, 12 of 22 cases with BIRADS 4 score were Triple negative (TN) while 5 of 47 cases with BIRADS 5 score were TN (p = 0.001). The patients with TN tumors were found to have lower average age, higher grade, higher Ki67 proliferative index and fewer lymph node metastasis than those with non-TN ductal carcinomas (p = 0.048; 0.019; 0.02; 0.048 respectively). Patients who had radiological BIRADS 4 score were significantly more frequent TN type carcinoma than BI-RADS 5. It is important to pay attention to this issue when clinicians evaluate patients with BI-RADS 4 score breast lesions.

  20. The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas

    PubMed Central

    Tille, Jean-Christophe; Ho, Liza; Shah, Jimit; Seyde, Olivia; McKee, Thomas A.; Citi, Sandra

    2015-01-01

    PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens), and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas. PMID:26270346

  1. Ductal carcinoma in a multiple fibroadenoma: diagnostic inaccuracies.

    PubMed

    Rao, Shalinee; Latha, P Suvarna; Ravi, A; Thanka, J

    2010-01-01

    We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

  2. Intrapancreatic distal common bile duct carcinoma: Analysis, staging considerations, and comparison with pancreatic ductal and ampullary adenocarcinomas.

    PubMed

    Gonzalez, Raul S; Bagci, Pelin; Basturk, Olca; Reid, Michelle D; Balci, Serdar; Knight, Jessica H; Kong, So Yeon; Memis, Bahar; Jang, Kee-Taek; Ohike, Nobuyuki; Tajiri, Takuma; Bandyopadhyay, Sudeshna; Krasinskas, Alyssa M; Kim, Grace E; Cheng, Jeanette D; Adsay, N Volkan

    2016-11-01

    Distal common bile duct carcinoma is a poorly characterized entity for reasons such as variable terminology and difficulty in determining site of origin of intrapancreatic lesions. We compared clinicopathologic features of pancreatobiliary-type adenocarcinomas within the pancreas, but arising from the distal common bile duct, with those of pancreatic and ampullary origin. Upon careful review of 1017 pancreatoduodenectomy specimens with primary adenocarcinoma, 52 (5%) qualified as intrapancreatic distal common bile duct carcinoma. Five associated with an intraductal papillary neoplasm were excluded; the remaining 47 were compared to 109 pancreatic ductal adenocarcinomas and 133 ampullary carcinomas. Distal common bile duct carcinoma patients had a younger median age (58 years) than pancreatic ductal adenocarcinoma patients (65 years) and ampullary carcinoma patients (68 years). Distal common bile duct carcinoma was intermediate between pancreatic ductal adenocarcinoma and ampullary carcinoma with regard to tumor size and rates of node metastases and margin positivity. Median survival was better than for pancreatic ductal adenocarcinoma (P=0.0010) but worse than for ampullary carcinoma (P=0.0006). Distal common bile duct carcinoma often formed an even band around the common bile duct and commonly showed intraglandular neutrophil-rich debris and a small tubular pattern. Poor prognostic indicators included node metastasis (P=0.0010), lymphovascular invasion (P=0.0299), and margin positivity (P=0.0069). Categorizing the tumors based on size also had prognostic relevance (P=0.0096), unlike categorization based on anatomic structures invaded. Primary distal common bile duct carcinoma is seen in younger patients than pancreatic ductal adenocarcinoma or ampullary carcinoma. Its prognosis is significantly better than pancreatic ductal adenocarcinoma and worse than ampullary carcinoma, at least partly because of differences in clinical presentation. Use of size-based criteria

  3. [Rare forms of the ductal carcinoma of the pancreas].

    PubMed

    Setdikova, G R; Filippova, E M; Paklina, O V; Kriger, A G; Chekmareva, I A; Gorin, D S; Berelavichus, S V; Bedin, V V; Tavobilov, M M

    2013-01-01

    Clinical cases of patients with rare forms of ductal pancreatic carcinoma are described. Difficulties of preoperative radiologic verification of ostheoclast-like giantcell tumor and cricoids-cell carcinoma of the pancreas are described. Morphologigic and immunohistochemical features of these tumors are highlighted. One of the clinical cases demonstrate the aggressive tumor behavior, led to liver metastases 4 months after the radical operation. Literature review highlights historical aspects and the state-of-art of diagnostics and treatment of rare forms of the ductal carcinoma of the pancreas.

  4. Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient

    PubMed Central

    Leonardi, Giulia Costanza; Ravaioli, Noemi; De Giglio, Andrea; Brambilla, Marta; Prosperi, Enrico; Ribacchi, Franca; Meacci, Marialuisa; Crinò, Lucio; Maiettini, Daniele; Chiari, Rita; Metro, Giulio

    2016-01-01

    Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis. PMID:27721883

  5. Ductal carcinoma in situ: a disease entity that merits more recognition.

    PubMed

    Dereere, E; Papadimitriou, K; Tjalma, W; Altintas, S

    2015-08-01

    Ductal carcinoma in situ (DCIS) is a non-invasive breast carcinoma that remains in the milk ducts. It is a poorly understood disease and its natural history is not well known. This is because once diagnosed, DCIS is usually treated. It is known however that ductal carcinoma is a precursor of invasive breast carcinoma, as 14-53% can become invasive over a period of 10 years, if left untreated. With increasing knowledge about the molecular biology of DCIS, more insight is given in its relation to invasive breast cancer. Diagnosis of ductal carcinoma in situ is increasing in the last few years. This is likely caused by the increased mammographic screening for breast cancer and the higher quality of mammographic images. DCIS represents about one fifth of all mammographically detected breast cancers. Risk factors for the development of ductal carcinoma in situ are: low parity, late age at first birth and menopause, and Body Mass Index. The Van Nuys Prognostic Index is a useful scoring system to grade DCIS. DCIS is graded by scoring four characteristics: patient's age, margin width, tumor size and pathological classification. It allows us to divide DCIS lesions into different groups according to risk of local recurrence: low risk, intermediate risk and high risk. Each group requires a different treatment, respectively: local excision of the tumor; local excision and radiotherapy; and mastectomy. The use of tamoxifen in the treatment of DCIS is still controversial, but research so far has encouraging results. Interesting developments have been made in the use of Her-2 pulsed dendritic cell vaccination before DCIS surgery.

  6. Treatment of ductal carcinoma in situ: an uncertain harm-benefit balance.

    PubMed

    2013-12-01

    Ductal carcinoma in situ develops in the milk ducts without invading the surrounding connective tissue. Progression to invasive carcinoma is slow and infrequent and is thus difficult to predict. Screening mammography has increased the number of women diagnosed with early-stage ductal carcinoma in situ. What is the best management strategy for patients whose breast biopsy suggests ductal carcinoma in situ? Is watchful waiting a reasonable option? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. Surgical resection is usually proposed to women with ductal carcinoma in situ but has not been compared with watchful waiting. Resection does not appear to have a major impact on mortality: trials of screening mammography showed no major reduction in breast cancer mortality, but screening does increase the number of diagnoses of ductal carcinoma in situ and, thus, the number of women who undergo surgery. When ductal carcinoma in situ is diagnosed by biopsy, histological examination of the surgically resected tumour reveals invasive breast cancer in about 13% to 24% of cases. Surgical removal of the tumour is usually proposed to women with ductal carcinoma in situ. Excision may be either localised (lumpectomy) or extensive (mastectomy). We found no randomised trials comparing the two approaches. Lumpectomy is usually proposed when the tumour is small (less than 20 mm) and appears to be amenable to complete excision with acceptable cosmetic results. A follow-up study of nearly 2000 women showed a recurrence rate of about 27% between 8 and 10 years after lumpectomy without further treatment. Mastectomy is usually proposed when the tumour appears to be extensive on mammography, or when complete resection with acceptable cosmetic results does not appear feasible, or when the patient chooses this option. Following mastectomy, the risk of carcinoma is similar to that of the general female population. Mastectomy and

  7. [CD147 expression in non-invasive and invasive breast carcinoma].

    PubMed

    Nagashima, Saki; Sakurai, Kenichi; Suzuki, Shuhei; Hara, Yukiko; Maeda, Tetsuyo; Hirano, Tomohisa; Enomoto, Katsuhisa; Amano, Sadao; Koshinaga, Tsugumichi

    2014-10-01

    CD147 is a multifunctional membrane glycoprotein involved in tumor invasion, and is overexpressed in many solid tumors. However, the role of CD147 in breast cancer is not well understood. The aim of this study was to evaluate CD147 expression in non-invasive and invasive ductal carcinomas. We recruited 156 breast cancer patients who underwent radical operations at our hospital up until 2002. We performed immunohistochemistry on their tumor specimens, and compared these data with clinicopathological factors. We divided the patients into two groups: group A was comprised of non-invasive ductal carcinomas and group B, invasive ductal carcinomas. The CD147-positive rate was 62.8% for all patients and was higher in group B than group A. In all cases, the CD147-positive rate correlated with clinical stage, number of metastatic lymph nodes, and tumor size. These results implied that CD147 may be involved in the process of breast cancer invasion.

  8. No impact of breast magnetic resonance imaging on 15-year outcomes in patients with ductal carcinoma in situ or early-stage invasive breast cancer managed with breast conservation therapy.

    PubMed

    Vapiwala, Neha; Hwang, Wei-Ting; Kushner, Carolyn J; Schnall, Mitchell D; Freedman, Gary M; Solin, Lawrence J

    2017-04-15

    For women undergoing breast conservation therapy (BCT), the added value of breast magnetic resonance imaging (MRI) at the time of initial diagnosis remains controversial. The current study was performed to determine long-term outcomes after BCT for women with and without pretreatment breast MRI. Between 1992 and 2001, a total of 755 women with ductal carcinoma in situ or early-stage invasive breast cancer underwent breast-conserving surgery (with axillary lymph node staging for invasive carcinoma) followed by definitive breast radiotherapy. Evaluation at the time of the initial diagnosis included conventional mammography in all subjects and breast MRI in 215 women (28%). Clinical, pathologic, and treatment characteristics were comparable for patients with and without breast MRI. Outcomes were determined using the Kaplan-Meier method and compared using the log-rank method. At a median follow-up of 13.8 years, there were 49 local failures (15 women with and 34 women without breast MRI, respectively). The 15-year local failure rates were 8% for women with and 8% for women without MRI (P = .59). There also were no differences noted between women with and without breast MRI with regard to 15-year rates of overall survival (77% vs 71%; P = .24), freedom from distant metastases (86% vs 90%; P = .08), and contralateral breast cancer (10% vs 8%; P = .10). Multivariate analysis demonstrated no significant impact of breast MRI on local failure (P = .96). Breast MRI during the initial evaluation for BCT appears to have no significant impact on 15-year rates for local control, overall survival, freedom from distant metastases, or contralateral breast cancer. The routine use of pretreatment breast MRI is not indicated for patients undergoing BCT. Cancer 2017;123:1324-1332. © 2016 American Cancer Society. © 2016 American Cancer Society.

  9. The Performance of Ki-67 Labeling Index in Different Specimen Categories of Invasive Ductal Carcinoma of the Breast Using 2 Scoring Methods.

    PubMed

    Al Nemer, Areej

    2017-02-01

    In breast carcinoma proliferative rate is not only prognostic, but also predictive factor. Ki-67 labeling index (Ki-67 LI) is a superior and more reproducible way to assess proliferation than counting mitoses. There are different Ki-67 LI cut-off values proposed for stratification. The best method of scoring Ki-67 LI is still controversial. Our aim was to test the consensus of Ki-67 LI read in the 2 most common specimens, diagnostic core biopsies (CNB) and surgical excision (SE), first using the hot spot (HS) for counting, and then the average (Av) Ki-67 LI. Cases diagnosed as having invasive duct breast carcinoma on CNB followed by SE over 6 years were recruited (n=96). Ki-67 LI was counted in both specimen types using HS and Av scoring methods. For both methods, agreement between the 2 specimen categories was tested using different cut-off values. Intraobserver reproducibility was also measured for both scoring methods. Ki-67 LI was significantly lower in CNBs compared with SEs (mean difference: -13.3 and -6.3, P<0.001, using HS and Av methods, respectively). The agreement between Ki-67 LI in CNBs and SEs using 10, 14, and 20 as cut-off value was superior when we used Av method (for κ=0.793, 0.814, and 0.745; vs. for HS: κ=0.542, 0.525, and 0.672, respectively). Intraobserver reproducibility ranged from very good to perfect for both methods. Our results suggested that specimen-specific cut-off value should be applied for both scoring methods.

  10. CD44 expression in intraoral salivary ductal papillomas and oral papillary squamous cell carcinoma.

    PubMed

    Fitzpatrick, Sarah G; Montague, Lindsay J; Cohen, Donald M; Bhattacharyya, Indraneel

    2013-06-01

    CD44 is a transmembrane adhesion molecule which has been previously shown to be useful in the differentiation of benign papillary lesions from invasive carcinoma in several different areas including sinonasal mucosa and breast tissue. CD44 expression has previously been shown to be lost in invasive carcinoma and retained in benign papillary lesions in both of the above locations. In addition, studies have evaluated oral mucosal lesions for CD44 expression and found a loss with invasive squamous cell carcinoma when compared to normal epithelium, hyperplasia, and squamous papillomas, which stained particularly strongly. To the best of our knowledge, no study has evaluated CD44 expression when comparing salivary ductal papillomas in comparison to oral papillary SCCA. In this study 18 cases of intraductal papilloma were compared to 19 cases of oral papillary SCCA. Within the ductal papilloma group, all cases stained either absent (6%), weakly (33%), or moderately (61%) with 76% expressing the stain diffusely and 24% focally. In comparison, the papillary squamous cell carcinoma cases expressed the CD44 moderately (26%) or strongly (74%) with 100 % showing diffuse staining. Thus, the CD44 expression was contrary to expectation based on previous studies, which we hypothesize is due to the extremely well differentiated nature of papillary SCCA which expressed CD44 staining compatible with levels previously reported with oral squamous papillomas than invasive carcinoma.

  11. Biochemical and ultrastructural correlations of calreticulin and thioredoxin expression in breast mucinous carcinoma and infiltrating ductal carcinoma non-special type.

    PubMed

    Baltatzis, G E; Gaitanarou, H; Arnogianaki, N; Misitzis, J; Voloudakis-Baltatzis, I E

    2011-02-01

    Mucinous infiltrating invasive ductal adenocarcinoma consists of 2-4% invasive breast cancer, but is a very interesting type due to its macroscopic similarity to non-special-type (NST) ductal carcinoma. The macroscopic similarity of mucinous and infiltrating ductal carcinoma NST adenocarcinomas consists of a loose and edematous stroma, which is often seen in portions of NST carcinoma and may mimic the mucin pools of mucinous carcinoma. In this study the authors examined the ultrastructural differences between mucinous carcinoma and infiltrating ductal carcinoma NST. They also examined the protein expression of the tissues by 2D electrophoresis due to their belief that from the results of these two levels it is possible to understand the changes that take place both in the ultrastructural and biochemical levels in these two types of breast cancer. The ultrastructural results from mucinous carcinoma have shown many changes in cytoplasmic organelles in comparison to normal samples, depending on the grade and the number of metastatic lymph nodes. At the 2D elecrophoresis level the authors studied two interesting polypeptides, calreticulin and thioredoxin. Both of these proteins were found in patterns of fibroadenoma, mucinous carcinoma, and NST carcinoma, but with different quantitative expression among them. In the future the quantitative differences of these two proteins may provide specific tumor markers for these two types of carcinoma.

  12. Collective invasion in ductal and lobular breast cancer associates with distant metastasis.

    PubMed

    Khalil, Antoine A; Ilina, Olga; Gritsenko, Pavlo G; Bult, Peter; Span, Paul N; Friedl, Peter

    2017-09-11

    Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary invasive ductal carcinoma (IDC), expressing E-cadherin, and E-cadherin negative invasive lobular carcinoma (ILC) and identified predominantly collective invasion patterns (86/86 samples) in both carcinoma types. Whereas collective invasion in IDC lesions retained adherens junctions, multicellular clusters and "Indian files" in ILC, despite the absence of adherens junctions (AJ) proteins E-cadherin and β-catenin, retained CD44 at cell-cell contacts. By histomorphological scoring and semi-automated image analysis, we show that the extent of collective invasion into the adipose tissue correlated with decreased distant metastasis-free survival (5-year follow-up; hazard ratio: 2.32 and 2.29, respectively). Thus, collective invasion represents the predominant invasion mode in breast cancer, develops distinct junctional subtypes in IDC and ILC, and associates with distant metastasis, suggesting a critical role in systemic dissemination.

  13. Controversies in the Treatment of Ductal Carcinoma in Situ.

    PubMed

    Barrio, Andrea V; Van Zee, Kimberly J

    2017-01-14

    Ductal carcinoma in situ (DCIS) accounts for 20% of all newly diagnosed breast cancers. Mastectomy was once the gold standard for the treatment of DCIS; however, breast-conserving surgery (BCS) has been adopted as the treatment of choice for patients with small, screen-detected lesions. Both adjuvant radiation and hormonal therapy following BCS have been demonstrated in randomized trials to reduce the risk of both invasive and DCIS recurrence, but neither affects survival. With the variety of surgical and adjuvant treatment options available, there has been great interest in tailoring the treatment to the individual, with the goal of optimizing the balance of risks and benefits according to the values and priorities of the woman herself. Prospective studies of women with "low-risk" DCIS treated with BCS alone have successfully identified women at lower than average risk but have not achieved the goal of identifying a subset of women with DCIS at minimal risk of recurrence after surgical excision alone. No studies have evaluated the safety of medical management alone.

  14. Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma.

    PubMed

    Leung, Lisa; Radulovich, Nikolina; Zhu, Chang-Qi; Organ, Shawna; Bandarchi, Bizhan; Pintilie, Melania; To, Christine; Panchal, Devang; Tsao, Ming Sound

    2012-01-01

    Lipocalin 2 (LCN2) is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease.

  15. Lipocalin2 Promotes Invasion, Tumorigenicity and Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Leung, Lisa; Radulovich, Nikolina; Zhu, Chang-Qi; Organ, Shawna; Bandarchi, Bizhan; Pintilie, Melania; To, Christine; Panchal, Devang; Tsao, Ming Sound

    2012-01-01

    Lipocalin 2 (LCN2) is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease. PMID:23056397

  16. Collision of Ductal Carcinoma In Situ of Anogenital Mammary-like Glands and Vulvar Sarcomatoid Squamous Cell Carcinoma.

    PubMed

    Tran, Tien A N; Deavers, Michael T; Carlson, J Andrew; Malpica, Anais

    2015-09-01

    A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

  17. Molecular markers for the diagnosis and management of ductal carcinoma in situ.

    PubMed

    Polyak, Kornelia

    2010-01-01

    Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions reflecting the proliferation of malignant cells within the ducts of the breast without invasion through the basement membrane. Numerous studies analyzing the molecular profiles of DCIS using genome-wide unbiased and candidate gene approaches have been conducted with the aim of identifying clinically useful markers that would predict the risk of progression to invasion. Results of these investigations defined the heterogeneity of DCIS at the molecular level, but a gene signature predictive of invasive progression has not been identified. Major diagnostic criteria that differentiate DCIS from invasive cancer are the presence of intact basement membrane and myoepithelial cell layer. Based on this, perturbation of normal myoepithelial cell differentiation has been proposed to explain progression to invasion. Comprehensive molecular studies analyzing large cohorts of DCIS with long-term clinical follow-up are necessary to resolve the many remaining questions.

  18. Hypofractionated Radiation Therapy for Breast Ductal Carcinoma In Situ

    SciTech Connect

    Hathout, Lara; Hijal, Tarek; Théberge, Valérie; Fortin, Bernard; Vulpe, Horia; Hogue, Jean-Charles; Lambert, Christine; Bahig, Houda; and others

    2013-12-01

    Purpose: Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. Methods and Materials: In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. Results: Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. Conclusions: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.

  19. Adjuvant treatment for pancreatic ductal carcinoma.

    PubMed

    Macarulla, T; Fernández, T; Gallardo, M E; Hernando, O; López, A M; Hidalgo, M

    2017-06-21

    Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a very poor prognosis. Most of the patients are diagnosed in advanced stages of the disease, and 5-year survival rates in these patients remains <10%. Surgery still remains the only radical treatment option, although only 15-20% of patients are candidates for surgical resection at the time of the diagnosis. Patients who undergo radical surgery still have a limited survival rate, being the average of 23 months. Three clinical trials have shown that adjuvant chemotherapy therapy after surgery may improve survival: CONKO-1, ESPAC-3, and ESPAC-4. Adjuvant therapy is recommended in patients with R0/R1, T1-4/N1-0 tumors and with ECOG 0-1. In patients with ECOG-2, the decision needs to be individualized. Treatment schemes that have demonstrated efficacy include gemcitabine alone, 5-fluorouracil, or the combination of gemcitabine and capecitabine for six months. Prior to adjuvant treatment, the following test are recommended: Complete blood tests, including CA19.9 biomarker; imaging studies to rule out early disease relapse (preferable thorax-abdomen-pelvic CT). Studies that have evaluated the efficacy of radiation therapy in the adjuvant setting have presented conflicting results. Its use should be considered in patients with R1 or R2 tumors or in those with lymph nodes involved.

  20. Clinicopathological features of infiltrating lobular carcinomas comparing with infiltrating ductal carcinomas: a case control study

    PubMed Central

    2010-01-01

    Background Infiltrating lobular carcinoma (ILC) is the second most common type of invasive breast cancers and it has been reported to have some unique biologic and epidemiologic characteristics. Methods Clinicopathological features of 95 patients with ILC, their relapse free survival (RFS) and overall survival (OS) were retrospectively investigated and compared with those of 3,621 patients with infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) between January 1984 and December 2005. Results ILC constitutes 2.3% of all invasive breast cancers. There were no difference between the ILC and the IDC-NOS groups regarding age at diagnosis, tumor size, nodal status, and treatment modalities except hormone therapy. The ILC group showed more estrogen receptor expression, less HER-2 expression and higher bilaterality. RFS and OS of the ILC patients were similar to those of the IDC. IDC-NOS metastasized more frequently to the lung and bone, whereas, ILC to the bone and ovary. Conclusions The incidence of ILC was relatively low in Korean breast cancer patients. Comparing to IDC-NOS ILC showed some different features such as higher estrogen receptor expression, less HER-2 expression, higher bilaterality and preferred metastatic sites of bone and ovary. Contralateral cancers and bone and ovary evaluation should be considered when monitoring ILC patients. PMID:20423478

  1. A Catalogue of Altered Salivary Proteins Secondary to Invasive Ductal Carcinoma: A Novel In Vivo Paradigm to Assess Breast Cancer Progression

    PubMed Central

    Streckfus, Charles F.; Bigler, Lenora

    2016-01-01

    The objective of this manuscript is to introduce a catalogue of salivary proteins that are altered secondary to carcinoma of the breast. The catalogue of salivary proteins is a compilation of twenty years of research by the authors and consists of 233 high and low abundant proteins which have been identified by LC-MS/MS mass spectrometry, 2D-gel analysis and by enzyme-linked immunosorbent assay. The body of research suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be useful in the study of breast cancer progress, treatment efficacy and the tailoring of individualized patient care. PMID:27477923

  2. Relevant infrastructural alterations in invasive pancreatic ductal adenocarcinoma.

    PubMed

    Constantin, Vlad Denis; Mirancea, Gabriel Valeriu; Moroşanu, Ana Maria; Mirancea, Nicolae

    2015-01-01

    In this study, we focus our interest on some peculiar infrastructural abnormalities detected in a pancreatic cancer case. Our electron microscopic observations underline the high plasticity of the pancreatic parenchyma cells. Tumor pancreatic exocrine lesions are represented by putative ductal and acinar cells, which proliferate and grow in a haphazard pattern, detrimental to endocrine counterpart. The tumor cells do not exhibit neither a pure ductular or ductal nor a pure acinar phenotype, but tumor lesions represented by neoplastic ductal cells with invasive growth are by far prevalently. In our pancreatic cancer case, electron microscopic investigation clearly shows that a plethora of the epithelial cells from the tumor lesions contain large areas of autophagy leading to the pleomorphic inclusions represented by fibrillary÷filamentous inclusions frequently associated with hyaline-amorphous material, and secondary lysosomes. One of the mostly striking and important finding in this report for a case of pancreatic cancer is the high fragility (extensive dissolutions) of plasma membrane of tumor cells leading to pseudo-syncytia formation. Desmosomal junctions are severely altered, almost missing. Plasma membranes showed shedding membrane vesicles. Extravasated inflammatory cells contribute to the dramatic and extensive destructive areas of epithelial cells as well as tumor-stroma counterpart, including the basement membrane. All above severe infrastructural abnormalities, especially down regulation of cell-cell and cell-extracellular matrix adhesions might result in aberrant cell behavior and, consequently, much care should be taken for the postoperatory patient evolution.

  3. Ductal carcinoma of the breast in the pacemaker generator's pocket.

    PubMed

    Zonca, P; Herokova, J; Cambal, M; Jacobi, C A

    2009-01-01

    Authors present a case of a 78-year-old female patient with invasive ductal adenocarcinoma in the pacemaker, s pocket. A decubitus-like tumor had developed in this place, and has been missinterpretated as a benign lesion for 5 months. Diagnosis was done with a time delay. An excisional biopsy revealed annvasive ductal adenocarcinoma. The first step was the implantation of a new pacemaker generator performed on the opposite side. The second step was a modified radical mastectomy, according to Madden, and the removal of the originally implanted pacemaker generator. Radiotherapy and hormonal adjuvant therapy were applied after surgery. The patient was followed-up at an out-patient clinic, and died 25 months after diagnosis because of generalization of the disease (Fig. 2, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

  4. [Breast cancer in males: a study of 15 cases of pure ductal carcinoma in situ].

    PubMed

    Cutuli, B F; Florentz, P; Lacroze, M; Dilhuydy, J M; Allavena, C; De Lafontan, B; Resbeut, M; Campana, F; Graic, Y; Tortochaux, J

    1992-01-01

    Ductal carcinoma in situ of the breast is very rare in men, representing 0-7% of all male breast cancers. We analysed 15 cases from a retrospective multicentric series of 404 patients (3.7%). It occurs earlier than infiltrating carcinoma (mean age: 55 years), sometimes before 40 years of age. The main symptoms are bloody nipple discharge or retro areolar mass. Modified radical mastectomy constitutes the basic treatment. Lower axillary dissection can eventually be indicated in comedocarcinoma or in tumors larger than 25 mm. The main histologic subgroup is papillary carcinoma, pure or intracystic. As is the case in women, local recurrence, invasive or not, rarely occurs. Theoretically, the cure rate approaches 100%. However, as in all cases of breast cancer in men, an important number of deaths due to secondary cancer or intercurrent disease have been noted. Until now, no clear etiologic factors have been found.

  5. Ductal Carcinoma In Situ: Treatment Update and Current Trends.

    PubMed

    Mitchell, Katrina B; Kuerer, Henry

    2015-11-01

    Ductal carcinoma in situ (DCIS) traditionally has been managed through various combinations of surgery, radiation, and endocrine therapy. However, concern for under- or over-treatment of DCIS has led many surgeons to question historically standardized approaches and instead begin to tailor treatment based on individual prognostic indicators. Recent and ongoing clinical trials have investigated the potential for active surveillance in DCIS, the possibility of eliminating radiation therapy (RT), and ways in which adjuvant systemic therapy may be refined. This review will summarize the current trends in the treatment of DCIS, as well as highlight the most pertinent clinical trials that are shaping management today.

  6. Status of Intraductal Therapy for Ductal Carcinoma in Situ

    PubMed Central

    Flanagan, Meghan; Love, Susan

    2010-01-01

    The intraductal approach is particularly appealing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understanding of the anatomy of the ductal system as well as novel techniques to leverage the access accorded by the intraductal approach, researchers are actively exploring how ductal lavage, ductoscopy, and intraductal infusion of therapeutic agents may enhance breast cancer treatment. Both cytologic and molecular diagnostics continue to improve, and work is ongoing to identify the most effective diagnostic biomarkers for DCIS and cancer, although optimal targeting of the diseased duct remains an important consideration. Ductoscopy holds potential in detection of occult intraductal lesions, and ductoscopically guided lumpectomy could increase the likelihood of a more comprehensive surgical excision. Exciting pilot studies are in progress to determine the safety and feasibility of intraductal chemotherapy infusion. These studies are an important starting point for future investigations of intraductal ablative therapy for DCIS, because as our knowledge and techniques evolve, it is likely that DCIS may be the target most amenable to treatment by intraductal therapy. If such studies are successful, these approaches will allow an important and meaningful transformation in treatment options for women diagnosed with DCIS. PMID:21124756

  7. A Rare Breast Tumor Confused with Ductal Carcinoma in Situ, Primary Solid Neuroendocrine Carcinoma

    PubMed Central

    Alıcı, Ömer; Aydoğdu, Serap Korkmaz

    2014-01-01

    The concept of pure neuroendocrine breast tumors was initially defined by Sapino et al. There are three sub-types of these tumors: solid, small cell/oat cell, and large cell neuroendocrine carcinomas. To diagnose neuroendocrine tumors, more than half of the tumor cells must have neuroendocrine differentiation. The possibility of metastatic neuroendocrine carcinoma must always be excluded in the differential diagnosis. In addition, it should be considered that solid neuroendocrine (NE) carcinomas can be confused with ductal carcinoma in situ due to their similar morphologic appearance. In this article, a patient with primary solid neuroendocrine breast cancer who had been diagnosed with ductal carcinoma in situ at another center was presented along with morphological and immunohistochemical features.

  8. An unusual cystic presentation of ductal carcinoma of the prostate.

    PubMed

    De Gobbi, Alberto; Morlacco, Alessandro; Valotto, Claudio; Vianello, Fabio; Zattoni, Filiberto

    2016-11-18

    A 74-year-old male came to our clinic for rectal tenesmus, lower urinary tract symptoms and a previous episode of acute retention of urine. Computed tomography (CT) and magnetic resonance imaging (MRI) scan of abdomen showed a multiloculated, cystic formation of 12 cm in the pelvic cavity to the left, with compression of the prostate, bladder, sigmoid and rectum, and its extension imprinted the back of the pubis and back bladder. Saturation prostate biopsy was negative for carcinoma. The histology of transurethral resection of bladder formation revealed flogistic tissue. Cistoprostatectomy and ureteroileal pouch with Wallace anastomosis, removal of the rectum and colostomy with Hartmann pouch were performed. The histopatology showed a ductal carcinoma of the prostate.

  9. Identification of a basal-like subtype of breast ductal carcinoma in situ.

    PubMed

    Livasy, Chad A; Perou, Charles M; Karaca, Gamze; Cowan, David W; Maia, Diane; Jackson, Susan; Tse, Chiu-Kit; Nyante, Sarah; Millikan, Robert C

    2007-02-01

    Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma.

  10. Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions.

    PubMed

    Mardekian, Stacey K; Bombonati, Alessandro; Palazzo, Juan P

    2016-03-01

    Ductal carcinoma in situ (DCIS) of the breast is a lesion characterized by significant heterogeneity, in terms of morphology, immunohistochemical staining, molecular signatures, and clinical expression. For some patients, surgical excision provides adequate treatment, but a subset of patients will experience recurrence of DCIS or progression to invasive ductal carcinoma (IDC). Recent years have seen extensive research aimed at identifying the molecular events that characterize the transition from normal epithelium to DCIS and IDC. Tumor epithelial cells, myoepithelial cells, and stromal cells undergo alterations in gene expression, which are most important in the early stages of breast carcinogenesis. Epigenetic modifications, such as DNA methylation, together with microRNA alterations, play a major role in these genetic events. In addition, tumor proliferation and invasion is facilitated by the lesional microenvironment, which includes stromal fibroblasts and macrophages that secrete growth factors and angiogenesis-promoting substances. Characterization of DCIS on a molecular level may better account for the heterogeneity of these lesions and how this manifests as differences in patient outcome and response to therapy. Molecular assays originally developed for assessing likelihood of recurrence in IDC are recently being applied to DCIS, with promising results. In the future, the classification of DCIS will likely incorporate molecular findings along with histologic and immunohistochemical features, allowing for personalized prognostic information and therapeutic options for patients with DCIS. This review summarizes current data regarding the molecular characterization of DCIS and discusses the potential clinical relevance.

  11. Long term clinical follow-up of atypical ductal hyperplasia and lobular carcinoma in situ in breast core needle biopsies.

    PubMed

    Renshaw, Andrew A; Gould, Edwin W

    2016-01-01

    Atypical ductal hyperplasia (ADH) and lobular carcinoma in situ (LCIS) may be associated with a relatively high incidence of invasive carcinoma and ductal carcinoma in situ (DCIS) on immediate excision when found on core needle biopsy of the breast. However, the long term significance of ADH and LCIS in a breast core needle biopsy is not as well characterised. We reviewed the results of all breast core needle biopsies with a diagnosis of ADH or LCIS and immediate excision from the years 2000-2004, and correlated the results with long term clinical follow-up. Of 175 biopsies with ADH, 53 (30.3%) had carcinoma (8 invasive, and 45 DCIS) at the time of immediate re-excision. Of 69 biopsies with LCIS, three (4.3%) had carcinoma (2 invasive, and 1 DCIS) at the time of immediate re-excision. A total of 14 (11.5%) patients with ADH and benign re-excisions developed invasive carcinoma (12) or DCIS (2) on follow-up. A total of 17 (25.8%) patients with LCIS and benign re-excisions developed invasive carcinoma (13) or DCIS (4) on follow-up. The risk of invasive carcinoma or DCIS on immediate re-excision was significantly higher for women with ADH than LCIS (p<0.001). Women with LCIS developed significantly more invasive carcinomas and DCIS than women with ADH on long term follow-up (p=0.01). Compared to women with fibrocystic changes (FCC) on core needle biopsy, the risk of developing invasive carcinoma or DCIS was significantly higher for women with ADH and benign initial re-excisions (95% CI 1.092-7.297, p=0.03), and women with LCIS and benign re-excisions (95% CI 3.028-18.657, p<0.001). Overall, 67/175 (38.3%) women with ADH and 20/69 (29.0%) women with LCIS on core needle biopsy either had carcinoma at the time of the biopsy or later developed carcinoma. Significantly more women with LCIS developed invasive carcinoma or DCIS than women with ADH on long term follow-up. The relative risk for ADH and LCIS on core biopsy with a negative excision compared with FCC was similar

  12. Use of magnetic resonance imaging for detecting clinically and mammographically occult ductal carcinoma in situ.

    PubMed

    Lo, G; Cheung, Polly S Y

    2008-06-01

    We report on two cases where breast magnetic resonance imaging examination changed clinical management. Breast magnetic resonance imaging is now recognised as an indispensable adjunctive examination to mammography and ultrasound. In each of the two cases described, breast magnetic resonance imaging revealed unsuspected, extensive, and mammographically and ultrasonologically occult, ductal carcinoma in situ. In each of these cases, planned breast conserving surgery was changed to mastectomy. The success of breast conservation treatment depends on removal of all tumour with clear margins at the time of surgery. Magnetic resonance imaging is now considered the most sensitive method for evaluating the extent of breast cancer. Breast magnetic resonance imaging has a very high sensitivity for invasive carcinoma (near 100%), and recent studies show its specificity in high-risk patients is between 93 and 99%. Magnetic resonance imaging may well be proven an important adjunctive examination in patients who have dense breasts or extensive fibrocystic change.

  13. Cystic hypersecretory ductal carcinoma of the breast: a rare cause of cystic breast mass.

    PubMed

    Song, Sun Wha; Whang, In Yong; Chang, Eun Deok

    2011-11-01

    We present the case of a surgically confirmed, invasive, cystic hypersecretory ductal carcinoma (CHDC) of the breast in a 43-year-old woman. The initial sonography showed a complex cyst, which required a core biopsy; however, the diagnosis was delayed as the patient refused to undergo the biopsy and the cyst decreased in size, as seen on follow-up sonography. Excision biopsy was performed, and invasive CHDC was diagnosed after regrowth of the cystic lesion. Meticulous sonographic evaluation of a cystic breast mass is always important, and pathology confirmation must be considered if the lesion shows features suspicious for malignancy, as a CHDC could be the cause of a cystic breast mass.

  14. Immunohistochemical and morphologic evaluation of primary cutaneous apocrine carcinomas and cutaneous metastases from ductal breast carcinoma.

    PubMed

    Fernandez-Flores, A

    2012-01-01

    The differential diagnosis between a primary cutaneous apocrine carcinoma (CAC) and a cutaneous metastasis from a breast carcinoma can be a very difficult task if it is only made on morphologic bases. Concerning adnexal tumors (in general), there have been many attempts to define an immunohistochemical panel, and while a definition is useful in certain respects, the series presented often times does not include examples of CAC. Other times, CAC seems to behave in an odd way in an immunohistochemical context; they behave differently than other adnexal tumors, and this in turn adds a grade of confusion to the differential diagnosis of a cutaneous metastasis. In the current study, we include seven cases of primary cutaneous apocrine tumors, including one carcinoma in situ, five infiltrating carcinomas, and one adenoma. Additionally, we examine the expression of estrogen receptors (ER), progesterone receptors (PR), and c-erbB-2. We also study myoepithelial markers, such as p63, D2-40, and SMA in them, as well as the pattern of expression of the following cytokeratins: CK7, CK8, CK18, CK19, CK5/6 and 34betaE12. On the other hand, we examine the expression of six immunohistochemical markers (ER, PR, p63, mammaglobin, CK5÷6 and D2-40) in 30 cases of cutaneous metastases from breast carcinoma, ductal type. None of our infiltrating primary CAC expressed ER or PR, while the cutaneous metastasis expressed the markers in 90% of the cases. D2-40 was expressed in 60% of the infiltrating CACs, while the metastases were either negative (93.33% of the cases) or positive with luminal reinforcement. Mammaglobin was a very useful marker, expressed by 66.66% of the metastases, and by only one CAC (and in less than 10% of the cells). None of the metastases were positive for p63, while 60% of the CAC expressed the marker. CK 5/6 was also expressed by a high percentage of our CACs (80%), while it was seen in only 6.66% of the metastases. We found SMA as a very useful tool in diagnosing

  15. [Ductal carcinoma in situ of the breast: role of imaging].

    PubMed

    Netter, E; Troufléau, P; Stinès, J

    1998-07-01

    The incidence of ductal carcinoma in situ (DCIS) has increased with the widespread use of screening mammography. DCIS is often suspected when clustered microcalcifications are evidenced on routinely performed mammography. High quality mammographies are required and should be completed with magnification views. Mammographic--pathologic correlations are described according to the new classifications as well as unusual forms of presentation on mammography. Early contrast enhancement in DCIS on dynamic MRI is reported and seems to be related with angiogenesis. A wire localization procedure of non-palpable lesions has to be performed and per-operative specimen radiography is mandatory. Stereotaxic large core needle biopsy is a valuable alternative to surgical biopsy but a multidisciplinary team approach is necessary and follow-up is recommended if no excisional biopsy is done. Quality in the management of DCIS depends on the coherence of the "multidisciplinary team".

  16. Ductal carcinoma in situ: recent history and areas of controversy.

    PubMed

    Lagios, Michael D; Silverstein, Melvin J

    2015-01-01

    The authors provide a perspective on the rapidly evolving field of prognostic analyses designed to quantify the risk of local recurrence in conservatively treated ductal carcinoma in situ (DCIS). These include morphologic features variously defined, nomograms, algorithms and multi-gene expression assays-all of which have completed against the perceived conclusions of the randomized trials of irradiation and Tamoxifen for DCIS: "all subsets benefit". At present the majority of newly diagnosed DCIS can be adequately treated with surgery alone. A number will require irradiation to achieve acceptable local control, and a minority will require mastectomy regardless of adjuvant treatments. Differences in the definition of prognostic factors and in the methods used to establish them is a major reason for the lack of consensus in treatment recommendation.

  17. Clinicopathological Features of Ductal Carcinoma In Situ from (18)F-FDG-PET Findings.

    PubMed

    Fujii, Takaaki; Yanai, Keiko; Tokuda, Shoko; Nakazawa, Yuko; Kurozumi, Sasagu; Obayashi, Sayaka; Yajima, Reina; Hirakata, Tomoko; Kuwano, Hiroyuki

    2017-09-01

    The presence of ductal carcinoma in situ (DCIS) can increase the risk of developing an invasive ductal carcinoma (IDC), but it is difficult to predict what will occur if a DCIS is left untreated. We reported the usefulness of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) for DCIS, and that the presence of FDG uptake in the tumor could be considered a predictor of invasive potential in patients with DCIS. In this study, we retrospectively evaluated the clinicopathological features of DCIS by using FDG-PET findings, and we evaluated the possibility of using FDG-PET in DCIS cases as a biomarker of which lesions will go on to become invasive. We investigated the cases of 185 consecutive patients with primary breast cancer who were diagnosed as having DCIS or IDC and underwent FDG-PET preoperatively. We divided the cases into two groups on the basis of histology; DCIS vs. IDC (n=171). The DCIS cases were divided into two groups on the basis of FDG uptake in the primary tumor. Fourteen of the 185 patients (7.4%) were revealed to have a DCIS. The analysis revealed that the SUVmax and the number of cases not detected by FDG-PET were significantly different between the DICS and IDC groups. The extent of the primary tumor was not significantly different between the two groups. In six cases (42.9%) of the 14 DCIS cases, no FDG uptake was detected by FDG-PET. The extent of tumor did not significantly differ between the two groups. In addition, all six cases without FDG uptake were of the diffuse-spread type, without mass formation. All eight cases with mass formation had FDG uptake. Our present findings suggest that the FDG-PET uptake reflects tumor burden or tumor density, which should be considered to be associated with the presence of invasion. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Opportunities for Molecular Epidemiological Research on Ductal Carcinoma In-situ and Breast Carcinogenesis: Interdisciplinary Approaches

    PubMed Central

    Sherman, Mark E.; Mies, Carolyn; Gierach, Gretchen L.

    2014-01-01

    Most invasive breast cancers arise from ductal carcinoma in-situ (DCIS), a non-obligate precursor of invasive breast cancer. Given that the natural history of individual DCIS lesions is unpredictable, many women with DCIS receive extensive treatments, which may include surgery, radiation and endocrine therapy, even though many of these lesions may have limited potential to progress to invasion and metastasize. In contrast to valid concerns about over-treatment, the fact that invasive breast cancers outnumber DCIS lesions by more than three-to-one, suggests that many cancer precursors (particularly DCIS, but LCIS also) progress to invasion prior to detection. Thus, DCIS poses a dual problem of over diagnosis among some women and failure of early detection among others. These concerns are heightened by the multi-fold increase in rates of DCIS in conjunction with widespread use of mammographic screening and access to outpatient radiologically-guided biopsies. Accordingly, methods are needed to both specifically detect and identify DCIS lesions with potential to progress to invasive cancer and to discover techniques to triage and conservatively manage indolent cases of DCIS. PMID:24225267

  19. Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

    PubMed

    Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

    2016-01-01

    Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

  20. Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study

    PubMed Central

    Catanzaro, Daniele; Schäffer, Alejandro A.; Schwartz, Russell

    2016-01-01

    Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with Synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints. PMID:26353381

  1. Risk stratification in ductal carcinoma in situ: the role of genomic testing.

    PubMed

    Freedman, Gary M

    2013-02-01

    From the earliest days of conservative surgery for ductal carcinoma in situ (DCIS) of the breast, there have been attempts to identify patients who may not need postoperative radiation. Randomized prospective trials have not identified a population for whom there is no benefit to radiation. However, decades of studies of clinical, radiological and pathologic correlates to local recurrence have led to criteria for a patient subgroup at low risk for local recurrence after omission of radiation. Gene expression profiling for invasive breast cancer has been used to identify patients at low, intermediate or high risk for distant recurrence. Application of this methodology to DCIS aims to identify patients at low, intermediate or high risk for local recurrence. Whether this method of risk stratification will prove more accurate than clinical, radiological and pathologic risk stratification, or identify patients with little to no clinical benefit from radiation, remains to be seen.

  2. [Breast MRI--histologic correlation for ductal carcinoma in situ].

    PubMed

    Neira, P; Aguirre, B; Taub, T; Gutiérrez, L; Sáez, C; Ibarra, A; Silva, C

    2009-01-01

    To evaluate the concordance between the breast MRI findings and the histologic findings for the size and extension of pure ductal carcinoma in situ (DCIS) and to compare this concordance with that of conventional techniques (mammography and ultrasonography). This is a retrospective study of consecutive patients diagnosed with DCIS after percutaneous biopsy. We estimated Lin's coefficient of concordance for the histologic findings with each of the three techniques. We also assessed concordance using Bland-Altman graphs. Finally, we determined the impact of the MRI findings on the surgical management of patients with DCIS. A total of 32 patients were included in the study. Concordance between imaging and histology on tumor size was higher for MRI (0.78; 95%CI, 0.62-0.87) than for mammography (0.43; 95%CI, 0.19-0.62) or for ultrasonography (0.27; 95%CI, 0.09-0.43). MRI overestimated the size of DCIS by a mean of 3 mm, whereas mammography and ultrasonography underestimated it by 9 mm and 18 mm, respectively. MRI detected multifocality and multicentricity (7 cases) better than mammography (3) or ultrasonography (0). The MRI findings correctly changed the surgical management in six patients. Breast MRI is better than conventional techniques for the evaluation of the size of DCIS. Breast MRI also detects more cases of multifocality and multicentricity. We recommend that all patients diagnosed with DCIS (especially those with dense breasts) undergo breast MRI prior to surgery.

  3. Preoperative Magnetic Resonance Imaging in Patients with Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.

    PubMed

    Brück, N; Koskivuo, I; Boström, P; Saunavaara, J; Aaltonen, R; Parkkola, R

    2017-04-01

    Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms. In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group ( p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group ( p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group ( p < 0.001). Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.

  4. Role of RNA binding protein HuR in ductal carcinoma in situ of the breast

    PubMed Central

    Heinonen, Mira; Hemmes, Annabrita; Salmenkivi, Kaisa; Abdelmohsen, Kotb; Vilén, Suvi-Tuuli; Laakso, Marko; Leidenius, Marjut; Salo, Tuula; Hautaniemi, Sampsa; Gorospe, Myriam; Heikkilä, Päivi; Haglund, Caj; Ristimäki, Ari

    2012-01-01

    HuR is a ubiquitously expressed RNA-binding protein that modulates gene expression at the post-transcriptional level. It is predominantly nuclear, but can shuttle between the nucleus and the cytoplasm. While in the cytoplasm HuR can stabilize its target transcripts, many of which encode proteins involved in carcinogenesis. While cytoplasmic HuR expression is a marker of reduced survival in breast cancer, its role in precursor lesions of malignant diseases is unclear. To address this we explored HuR expression in atypical ductal hyperplasia (ADH) and in ductal in situ carcinomas (DCIS). We show that cytoplasmic HuR expression is elevated in both ADH and DCIS when compared to normal controls, and that this expression associated with high grade, progesterone receptor negativity and microinvasion and/or tumour-positive sentinel nodes of the DCIS. To study the mechanisms of HuR in breast carcinogenesis, HuR expression was silenced in an immortalized breast epithelial cell line (184B5Me), which led to reduction in anchorage-independent growth, increased programmed cell death and inhibition of invasion. In addition, we identified two novel target transcripts (CTGF and RAB31) that are regulated by HuR and that bind HuR protein in this cell line. Our results show that HuR is aberrantly expressed at early stages of breast carcinogenesis and that its inhibition can lead to suppression of this process. PMID:21480233

  5. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    SciTech Connect

    Suhane, Sonal; Berel, Dror; Ramanujan, V. Krishnan

    2011-09-09

    Highlights: {yields} We monitored mitochondrial NDUFS3 expression in clinical breast cancer specimens. {yields} NDUFS3 expression is significantly higher in highly invasive cancer specimens. {yields} Increased NDUFS3 expression correlates with tumor nuclear grade. {yields} NDUFS3 expression in invasive ductal carcinoma is a potential hypoxia marker. -- Abstract: We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.

  6. Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer.

    PubMed

    Truin, Wilfred; Roumen, Rudi M; Siesling, Sabine; van der Heiden-van der Loo, Margriet; Lobbezoo, Dorien J; Tjan-Heijnen, Vivianne C; Voogd, Adri C

    2016-08-01

    Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification outcomes. We evaluated the effect of axillary staging procedures and subsequent axillary nodal status in patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) from 1998 to 2013. The use of SLN biopsy and the nodal status distribution were analyzed in patients with stage T1-T2 ILC and IDC. Logistic regression analysis was performed to determine the independent effect of histologic type on the probability of the presence of isolated tumor cells (ITCs), micrometastases, and macrometastases. A total of 89,971 women were diagnosed, 10,146 with ILC (11%) and 79,825 with IDC (89%). The patients who had undergone SLN biopsy were more frequently diagnosed with ITCs than were those who had undergone axillary lymph node dissection only (odds ratio, 8.8; 95% confidence interval, 7.0-11.2). In 2013, the proportion of patients with ITCs in the axillary nodes was 8% in those with ILC and 4.4% in those with IDC. Patients with ILC were significantly more likely to have ITCs in their axillary lymph nodes than were patients with IDC (odds ratio, 1.8; 95% confidence interval, 1.6-2.0). With the introduction of SLN biopsy and the renewed 2002 TNM classification, patients with ILC have been more frequently diagnosed with ITCs than have patients with IDC. The clinical consequence of this finding must be established from further research. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Ductal carcinoma in situ: Is core needle biopsy ever enough?

    PubMed

    Caswell-Smith, Peter; Wall, Madeleine

    2017-02-01

    This study investigates the rate of histological underestimation of invasive breast carcinoma following diagnosis of ductal carcinoma in situ (DCIS) on a radiologically guided core needle biopsy, and factors that may influence this upgrade rate. A retrospective review of the results of breast core biopsies performed between 1st January, 2005 and 2nd July, 2014 was conducted, and those with a diagnosis of DCIS were identified. Data including final excision pathology, lesion size, performing radiologist, core biopsy system and guidance method used were collected and included in the analysis. We report an overall upgrade rate to invasive cancer of 20.5% (95% CI = 16.1-24.9%). No statistically significant relationship was identified between biopsy systems used or clinicians performing the biopsies and the rate of upgrade to invasive cancer. Initially a statistically significant relationship was demonstrated between upgrade rates and lesion size, DCIS grade, as well as guidance method. Subsequent multivariable analysis showed no statistically significant relationship between guidance method and upgrade rates but a trend towards statistical significance (P < 0.1). Our recommendation is to inform women diagnosed with DCIS preoperatively in our programme, that there is a one in five chance the diagnosis will prove to be invasive cancer on definitive surgery. This is particularly important for women contemplating whether or not to undergo surgery for DCIS. Additionally, as the most significant predictor of upgrade rate demonstrated in this study is increasing lesion size, consideration should be given to increasing the number of core samples taken of larger lesions. © 2016 The Royal Australian and New Zealand College of Radiologists.

  8. Copy number analysis of ductal carcinoma in situ with and without recurrence.

    PubMed

    Gorringe, Kylie L; Hunter, Sally M; Pang, Jia-Min; Opeskin, Ken; Hill, Prue; Rowley, Simone M; Choong, David Y H; Thompson, Ella R; Dobrovic, Alexander; Fox, Stephen B; Mann, G Bruce; Campbell, Ian G

    2015-09-01

    Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer and a frequent mammographic finding requiring treatment. Up to 25% of DCIS can recur and half of recurrences are invasive, but there are no reliable biomarkers for recurrence. We hypothesised that copy number aberrations could predict likelihood of recurrence. We analysed a cohort of pure DCIS cases treated only with wide local excision for genome-wide copy number and loss of heterozygosity using Affymetrix OncoScan MIP arrays. Cases included those without recurrence within 7 years (n = 25) and with recurrence between 1 and 5 years after diagnosis (n = 15). Pure DCIS were broadly similar in copy number changes compared with invasive breast cancer, with the consistent exception of a greater frequency of ERBB2 amplification in DCIS. There were no significant differences in age or ER status between the cases with a recurrence vs those without. Overall, the DCIS cases with recurrence had more copy number events than the DCIS without recurrence. The increased copy number appeared non-random with several genomic regions showing an increase in frequency in recurrent cases, including 20 q gain, ERBB2 amplification and 15q loss. Copy number changes may provide prognostic information for DCIS recurrence, but validation in additional cohorts is required.

  9. Vascular invasion in infiltrating ductal adenocarcinoma of the pancreas can mimic pancreatic intraepithelial neoplasia: a histopathologic study of 209 cases.

    PubMed

    Hong, Seung-Mo; Goggins, Michael; Wolfgang, Christopher L; Schulick, Richard D; Edil, Barish H; Cameron, John L; Handra-Luca, Adriana; Herman, Joseph M; Hruban, Ralph H

    2012-02-01

    Although vascular invasion is a well-established indicator of poor prognosis for patients with infiltrating ductal adenocarcinoma of the pancreas (PDAC), the histopathologic characteristics of vascular invasion are not well described. Hematoxylin and eosin-stained slides from 209 surgically resected infiltrating PDACs were systematically evaluated for the presence or absence of microscopic vascular invasion. For the cases with vascular invasion, we further categorized the histologic pattern of invasion into conventional and pancreatic intraepithelial neoplasia-like (PanIN-like). In addition, several histopathologic factors in the surrounding blood vessels, including lymphocytic infiltration and luminal fibrosis, were carefully assessed. Data were compared with clinicopathologic variables, including patient survival. Microscopic vascular invasion was observed in 136 of the 209 PDACs (65.1%). Vascular invasion mimicking pancreatic intraepithelial neoplasia (PanIN-like invasion) was observed in 94 of the 136 cases (69.1%) with vascular invasion. Microscopic vascular invasion was associated with increased tumor size (P=0.04), higher pT classification (P=0.003), lymph node metastasis (P<0.0001), and perineural invasion (P=0.005). Vascular invasion was inversely correlated with neo-adjuvant therapy (P<0.0001). Examination of adjacent blood vessels revealed that peritumoral blood vessels with intimal lymphocytes (P=0.002), intimal (P=0.007) and medial (P=0.001) fibrosis, and cancer cells in vascular wall (P<0.0001) were all highly associated with the intraluminal vascular invasion. In univariate analysis, patients whose cancers had microscopic vascular invasion (median survival, 15.3 mo) had a significantly worse survival than did patients with carcinomas without vascular invasion (25.1 mo; P=0.01, log-rank test). Microscopic vascular invasion is a poor prognostic indicator and can histologically mimic PanIN.

  10. Patterns of care for ductal carcinoma in situ of the breast: Queensland's experience over a decade.

    PubMed

    Barbour, Samantha; Moore, Julie; Dunn, Nathan; Effeney, Rachel; Harden, Hazel; McCarthy, Alexandra; Walpole, Euan; Lehman, Margot

    2017-10-01

    To review management of ductal carcinoma in situ (DCIS) of the breast in Queensland, with reference to breast conserving surgery (BCS) and adjuvant radiation therapy (RT). In addition, we examined the incidence of invasive breast cancer recurrence and factors predictive of invasive recurrence. A retrospective review of the Queensland Oncology Repository identified women with resected DCIS (TisN0) ± adjuvant RT between 2003 and 2012. Time to invasive breast cancer recurrence was analysed using the Kaplan Meier method. Median follow-up was 4.9 years. 3038 women had surgery. 940 (31%) had mastectomy and 2098 (69%) underwent BCS. Of 2098 women having BCS, 1100 (52%) received BCS alone and 998(48%) received adjuvant RT. The use of RT significantly increased over the decade from 25% to 62% (p=<0.001). Clinicopathological factors associated with RT use on multivariate analysis included age ≤70, higher socioeconomic status, larger tumour size, higher nuclear grade and surgical margins ≤5 mm. Invasive breast cancer recurrence at 5 years was 1.7% [95% CI 1.0-3.0] in RT group versus 2.8% [95% CI 2.1-3.8] in BCS alone group. Factors associated with increased risk of invasive recurrence on multivariate analysis were age <40 and surgical margins ≤2 mm. The use of adjuvant RT in Queensland significantly increased between 2003 and 2012. Selection of patients for RT was based on clinicopathological factors associated with higher recurrence risk. Although longer follow-up is required, the selective use of radiation therapy after BCS is associated with a low rate of invasive breast cancer recurrence at 5 years. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  11. Can upstaging of ductal carcinoma in situ be predicted at biopsy by histologic and mammographic features?

    NASA Astrophysics Data System (ADS)

    Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

    2017-03-01

    Reducing the overdiagnosis and overtreatment associated with ductal carcinoma in situ (DCIS) requires accurate prediction of the invasive potential at cancer screening. In this work, we investigated the utility of pre-operative histologic and mammographic features to predict upstaging of DCIS. The goal was to provide intentionally conservative baseline performance using readily available data from radiologists and pathologists and only linear models. We conducted a retrospective analysis on 99 patients with DCIS. Of those 25 were upstaged to invasive cancer at the time of definitive surgery. Pre-operative factors including both the histologic features extracted from stereotactic core needle biopsy (SCNB) reports and the mammographic features annotated by an expert breast radiologist were investigated with statistical analysis. Furthermore, we built classification models based on those features in an attempt to predict the presence of an occult invasive component in DCIS, with generalization performance assessed by receiver operating characteristic (ROC) curve analysis. Histologic features including nuclear grade and DCIS subtype did not show statistically significant differences between cases with pure DCIS and with DCIS plus invasive disease. However, three mammographic features, i.e., the major axis length of DCIS lesion, the BI-RADS level of suspicion, and radiologist's assessment did achieve the statistical significance. Using those three statistically significant features as input, a linear discriminant model was able to distinguish patients with DCIS plus invasive disease from those with pure DCIS, with AUC-ROC equal to 0.62. Overall, mammograms used for breast screening contain useful information that can be perceived by radiologists and help predict occult invasive components in DCIS.

  12. A Molecular Portrait of High-Grade Ductal Carcinoma In Situ

    PubMed Central

    Abba, Martin C.; Gong, Ting; Lu, Yue; Lee, Jaeho; Zhong, Yi; Lacunza, Ezequiel; Butti, Matias; Takata, Yoko; Gaddis, Sally; Shen, Jianjun; Estecio, Marcos R.; Sahin, Aysegul A.; Aldaz, C. Marcelo

    2016-01-01

    Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. PMID:26249178

  13. Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features.

    PubMed

    Hendry, Shona; Pang, Jia-Min B; Byrne, David J; Lakhani, Sunil R; Cummings, Margaret C; Campbell, Ian G; Mann, G Bruce; Gorringe, Kylie L; Fox, Stephen B

    2017-09-01

    Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown.Experimental Design: We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number (n = 55) and mutation data (n = 20).Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%). Most DCIS were negative for tumor cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high-grade (P = 0.002/0.035), ER-negative (P = 0.02/0.02), and ERBB2-amplified tumors (P < 0.001/0.048). Comedo necrosis was significantly positively associated with TILs (P < 0.0001) but not with PD-L1. The TILs score was significantly higher in cases with TP53 mutation (P = 0.03) but not with PIK3CA or GATA3 mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both P < 0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels.Conclusions: Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumor copy number with the immune microenvironment, possibly by the immunoediting of the tumor. Clin Cancer Res; 23(17); 5210-7. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case control study

    PubMed Central

    Calvocoressi, Lisa; Stowe, Meredith H.; Carter, Darryl; Claus, Elizabeth B.

    2013-01-01

    Background and aim The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case control study in Connecticut, USA. Methods This analysis included 1,179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case-control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals. Results We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR) = 0.85, 95 % confidence interval (CI): 0.65-1.11); of estrogen alone (adjusted OR = 0.93; 95 % CI: 0.68-1.29) or of estrogen and progesterone (adjusted OR = 0.75; 95 % CI: 0.52-1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. Conclusions These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta-analyses of available data. PMID:22317899

  15. Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

    PubMed

    Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

    2016-06-02

    Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies.

  16. Automated Reconstruction Algorithm for Identification of 3D Architectures of Cribriform Ductal Carcinoma In Situ

    PubMed Central

    Norton, Kerri-Ann; Namazi, Sameera; Barnard, Nicola; Fujibayashi, Mariko; Bhanot, Gyan; Ganesan, Shridar; Iyatomi, Hitoshi; Ogawa, Koichi; Shinbrot, Troy

    2012-01-01

    Ductal carcinoma in situ (DCIS) is a pre-invasive carcinoma of the breast that exhibits several distinct morphologies but the link between morphology and patient outcome is not clear. We hypothesize that different mechanisms of growth may still result in similar 2D morphologies, which may look different in 3D. To elucidate the connection between growth and 3D morphology, we reconstruct the 3D architecture of cribriform DCIS from resected patient material. We produce a fully automated algorithm that aligns, segments, and reconstructs 3D architectures from microscopy images of 2D serial sections from human specimens. The alignment algorithm is based on normalized cross correlation, the segmentation algorithm uses histogram equilization, Otsu's thresholding, and morphology techniques to segment the duct and cribra. The reconstruction method combines these images in 3D. We show that two distinct 3D architectures are indeed found in samples whose 2D histological sections are similarly identified as cribriform DCIS. These differences in architecture support the hypothesis that luminal spaces may form due to different mechanisms, either isolated cell death or merging fronds, leading to the different architectures. We find that out of 15 samples, 6 were found to have ‘bubble-like’ cribra, 6 were found to have ‘tube-like’ criba and 3 were ‘unknown.’ We propose that the 3D architectures found, ‘bubbles’ and ‘tubes’, account for some of the heterogeneity of the disease and may be prognostic indicators of different patient outcomes. PMID:22970156

  17. Accelerated Partial Breast Irradiation for Pure Ductal Carcinoma in Situ

    SciTech Connect

    Park, Sean S.; Grills, Inga Siiner; Chen, Peter Y.; Kestin, Larry L.; Ghilezan, Michel I.; Wallace, Michelle; Martinez, Alvaro M.; Vicini, Frank A.

    2011-10-01

    Purpose: To report outcomes for ductal carcinoma in situ (DCIS) treated with breast-conserving therapy using accelerated partial breast irradiation (APBI). Methods and Materials: From March 2001 to February 2009, 53 patients with Stage 0 breast cancer were treated with breast conserving surgery and adjuvant APBI. Median age was 62 years. All patients underwent excision with margins negative by {>=}1 mm before adjuvant radiotherapy (RT). A total of 39 MammoSite brachytherapy (MS) patients and 14 three-dimensional conformal external beam RT (3DCRT) patients were treated to the lumpectomy bed alone with 34 Gy and 38.5 Gy, respectively. Of the DCIS cases, 94% were mammographically detected. All patients with calcifications had either specimen radiography or postsurgical mammography confirmation of clearance. Median tumor size was 6 mm, and median margin distance was 5 mm. There were no statistically significant differences according to APBI method for race/ethnicity, tumor detection method, tumor grade, estrogen receptor (ER) status, or use of tamoxifen (p = NS). Recurrence and survival were calculated using the Kaplan-Meier method. Cosmesis was scored by the Harvard criteria. Results: With a median follow-up of 3.6 years (range, 0.4-6.3 years), the overall and cause-specific survival rates were 98% and 100%, respectively. Three-year actuarial ipsilateral breast tumor recurrence was 2%. One failure was observed at the resection bed 11 months post-RT. No other elsewhere breast failures, regional recurrences, or distant metastases were noted. Cosmesis was excellent or good in 92.4% of cases, with no statistically significant differences according to the APBI method (92.3% with MammoSite and 92.8% with 3DCRT; p = 0.649). Conclusions: APBI as part of breast-conserving therapy for pure DCIS was associated with excellent local control and survival rates, with the vast majority of patients having good to excellent cosmesis. This finding supports the recent analysis by the

  18. Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ

    PubMed Central

    Meyerson, Anna F.; Lessing, Juan N.; Itakura, Kaoru; Hylton, Nola M.; Wolverton, Dulcy E.; Joe, Bonnie N.; Esserman, Laura J.; Hwang, E. Shelley

    2014-01-01

    Introduction An option for active surveillance is not currently offered to patients with ductal carcinoma in situ (DCIS); however a small number of women decline standard surgical treatment for noninvasive cancer. The purpose of this study was to assess outcomes in a cohort of 14 well-informed women who elected non-surgical active surveillance with endocrine treatment alone for estrogen receptor-positive DCIS. Methods Retrospective review of 14 women, 12 of whom were enrolled in an IRB-approved single-arm study of 3 months of neoadjuvant endocrine therapy prior to definitive surgical management. The patients in this report withdrew from the parent study opting instead for active surveillance with endocrine treatment and imaging. Results 8 women had surgery at a median follow up of 28.3 months (range 10.1–70 months), 5 had stage I IDC at surgical excision, and 3 had DCIS alone. 6 women remain on surveillance without evidence of invasive disease for a median of 31.8 months (range 11.8–80.8 months). Conclusion Long-term active surveillance for DCIS is feasible in a well-informed patient population, but is associated with risk of invasive cancer at surgical excision. PMID:21843942

  19. Dietary patterns and risk of ductal carcinoma of the breast: a factor analysis in Uruguay.

    PubMed

    Ronco, Alvaro L; De Stefani, Eduardo; Deneo-Pellegrini, Hugo; Boffetta, Paolo; Aune, Dagfinn; Silva, Cecilia; Landó, Gabriel; Luaces, María E; Acosta, Gisele; Mendilaharsu, María

    2010-01-01

    Breast cancer (BC) shows very high incidence rates in Uruguayan women. The present factor analysis of ductal carcinoma of the breast, the most frequent histological type of this malignancy both in Uruguay and in the World, was conducted at a prepaid hospital of Montevideo, Uruguay. We identified 111 cases with ductal BC and 222 controls with normal mammograms. A factor analysis was conducted using 39 food groups, allowing retention of six factors analyzed through logistic regression in order to obtain odds ratios (OR) associated with ductal BC. The low fat and non-alcoholic beverage patterns were inversely associated (OR=0.30 and OR=0.45, respectively) with risk. Conversely, the fatty cheese pattern was positively associated (OR=4.17) as well as the fried white meat (OR=2.28) and Western patterns (OR 2.13). Ductal BC shared similar dietary risk patterns as those identified by studies not discriminating between histologic type of breast cancer.

  20. Regressive change in high-grade ductal carcinoma in situ of the breast: histopathologic spectrum and biologic importance.

    PubMed

    Wasserman, Jason K; Parra-Herran, Carlos

    2015-09-01

    High-grade ductal carcinoma in situ (HG-DCIS) of the breast often shows tumor attenuation and reactive fibrosis. These changes, previously described as "regressive," have been paradoxically associated with an increased risk of invasive carcinoma. We aimed to further characterize the spectrum of the so-called regressive changes (RCs) in HG-DCIS. We reviewed 52 consecutive cases of HG-DCIS on biopsy specimens followed by excision. RCs were divided into early (stage 1) and advanced (stages 2 and 3) stages according to the degree of ductal fibrosis and tumor effacement. The presence of inflammation, hormone receptor status, and diagnosis on excision were recorded. RCs were seen in 51 (98%) cases: 96%, 76.4%, and 39.2% cases showed stages 1, 2, and 3, respectively. Periductal T cells with a normal CD4/CD8 ratio were constantly seen. Advanced RCs and inflammation were more frequent in estrogen and progesterone receptor-negative tumors. RCs were not associated with invasion but correlated with a larger residual HG-DCIS volume on excision. Regression in HG-DCIS is frequent. It may reflect a targeted immune response to certain phenotypes, mainly hormone receptor-negative lesions. Nonetheless, RCs do not lead to complete tumor obliteration but correlate with aggressive tumor characteristics instead. Copyright© by the American Society for Clinical Pathology.

  1. The organochlorine pesticides residues in the invasive ductal breast cancer patients.

    PubMed

    Yang, Jing-Zhe; Wang, Zhu-Xin; Ma, Li-Hui; Shen, Xing-Bin; Sun, Yu; Hu, Da-Wei; Sun, Li-Xin

    2015-11-01

    Investigation of organochlorine pesticides residues (important environmental contamination causing malignant transformation) in breast cancer patients is valuable to understanding their roles in breast cancer. 75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of β-HCH and PCTA were higher in IDC than those in both controls (both p<0.05), and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of β-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of β-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC (all p<0.05). The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.

  2. Identification of lesion subtypes in biopsies of ductal carcinoma in situ of the breast using biomarker ratio imaging microscopy

    PubMed Central

    Clark, Andrea J.; Petty, Howard R.

    2016-01-01

    Although epidemiological studies propose aggressive and non-aggressive forms of ductal carcinoma in situ (DCIS), they cannot be identified with conventional histopathology. We now report a retrospective study of human biopsy samples using biomarker ratio imaging microscopy (BRIM). Using BRIM, micrographs of biomarkers whose expression correlates with breast cancer aggressiveness are divided by micrographs of biomarkers whose expression negatively correlates with aggressiveness to create computed micrographs reflecting aggressiveness. The biomarker pairs CD44/CD24, N-cadherin/E-cadherin, and CD74/CD59 stratified DCIS samples. BRIM identified subpopulations of DCIS lesions with ratiometric properties resembling either benign fibroadenoma or invasive carcinoma samples. Our work confirms the existence of distinct subpopulations of DCIS lesions, which will likely have utility in breast cancer research and clinical practice. PMID:27247112

  3. Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis.

    PubMed

    Koca, İrfan; Özgür, Aykut; Er, Muhammet; Gümüş, Mehmet; Açikalin Coşkun, Kübra; Tutar, Yusuf

    2016-10-21

    Invasive ductal carcinoma is the most common breast malignancies tumors and has tendency to bone metastases. Many oncogenic client proteins involved in formation of metastatic pathways. Stabilization, regulation, and maintenance of these oncogenic client proteins are provided with Heat Shock Protein 90 (Hsp90). Hsp90 perform these processes through its ATP binding and subsequent hydrolysis energy. Therefore, designing Hsp90 inhibitors is a novel cancer treatment method. However, many Hsp90 inhibitors have solubility problems and showed adverse effects in clinical trials. Thus, we designed and synthesized novel pyrimidinyl acyl thiourea derivatives to selectively inhibit Hsp90 alpha in human invasive ductal breast (MCF-7) and human bone osteosarcoma (Saos-2) cell lines. In vitro experiments showed that the compounds inhibited cell proliferation, ATP hydrolysis, and exhibited cytotoxic effect on these cancer cell lines. Further, gene expression was analyzed by microarray studies on MCF-7 cell lines. Several genes that play vital roles in breast cancer pathogenesis displayed altered gene expression in the presence of a selected pyrimidinyl acyl thiourea compound. Molecular docking studies were also performed to determine interaction between Hsp90 ATPase domain and pyrimidinyl acyl thiourea derivatives. The results indicated that the compounds are able to interact with Hsp90 ATP binding pocket and inhibit ATPase function. The designed compounds powerfully inhibit Hsp90 by an average of 1 μM inhibition constant. And further, the compounds perturb Hsp90 N terminal domain proper orientation and ATP may not provide required conformational change for Hsp90 function as evidenced by in silico experiments. Therefore, the designed compounds effectively inhibited both invasive ductal breast carcinoma and bone metastasis. Pyrimidinyl acyl thiourea derivatives may provide a drug template for effective treatment of invasive ductal breast carcinoma and its bone metastasis as

  4. Ductal carcinoma in situ in core needle biopsies and its association with extensive in situ component in the surgical specimen

    PubMed Central

    2012-01-01

    Background We evaluated the presence of ductal carcinoma in situ (DCIS) in core needle biopsies (CNB) from invasive ductal lesions. Methods Retrospective study, which analyzed 90 cases of invasive ductal carcinoma lesions. The percentage of DCIS was quantified in each specimens obtained from CNB, which were compared to the surgical specimens. CNB and surgical specimens were evaluated by the same pathologist, and the percentage of DCIS in CNB was evaluated (percentage) and divided into categories. We considered the following parameters regarding the amount of DCIS: 1 = 0; 2 = 1 for 5%; 3 = 6 for 24%; 4 = 25 for 50%; 5 = 51 for 75% and 6 = 76 for 99%. The number of fragments and the histological pattern of DCIS was found. Results We found the following results regarding the distribution of the percentage of DCIS in the CNB: 1 = 63.3%; 2 = 12.2%; 3 = 12.2%; 4 = 5.6%; 5 = 1.1% and 6 = 5.6%. The logistic regression analysis showed that CNB percentages above 45% reflected the presence of DCIS in the surgical specimen in 100% of the cases (p < 0.001), with a specificity of 100%, accuracy of 83.3% and false positive rate of 0% (p <0.001). Conclusion There is direct relationship between extensive intraductal component in the surgical specimen when the core biopsy shows 45% or more of the DCI or microinvasive in the material examined. PMID:22715888

  5. Estrogen Receptor and Cytokeratin 5 Are Reliable Markers to Separate Usual Ductal Hyperplasia From Atypical Ductal Hyperplasia and Low-Grade Ductal Carcinoma In Situ.

    PubMed

    Martinez, Anthony P; Cohen, Cynthia; Hanley, Krisztina Z; Li, Xiaoxian Bill

    2016-07-01

    -High-molecular weight cytokeratins, such as cytokeratin 5 (CK5), are helpful to distinguish usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH) or low-grade ductal carcinoma in situ (DCIS). Few studies have looked at combining CK5 with estrogen receptor (ER) to differentiate UDH from ADH. -To evaluate the expression pattern of CK5 and ER as single or combined markers to separate UDH from ADH and low-grade DCIS. -A total of 23 ADH, 10 low-grade DCIS, and 32 UDH whole-tissue slides were stained for ER, CK5, progesterone receptor (PR), and Bcl-2. Nuclear staining of ER and PR was scored as diffuse (>80%), focal (10%-80%), or negative (<10%). Cytoplasmic staining of CK5 and Bcl-2 was scored as diffuse (>60%), focal (10%-60%), or negative (<10%). Differences in staining patterns were evaluated. -For ER staining: 94% of ADH/DCIS cases showed a diffuse staining pattern, whereas none of the 32 UDH cases showed diffuse staining. For CK5 staining: 96% of ADH/DCIS cases were negative or focally positive, whereas all 32 UDH cases had diffuse staining. The combination of ER and CK5 increased the sensitivity (94% to 97%). For PR staining: 11 of 23 ADH cases (48%), 6 of 10 DCIS cases (60%), and 4 of 32 UDH cases (13%) showed diffuse staining. Bcl-2 staining showed no statistical significance (P = .73). -Although morphology remains the gold standard, ER and CK5 are useful makers to differentiate UDH from ADH. Progesterone receptor staining may have limited value, and Bcl-2 staining is not useful.

  6. Is Sentinel Lymph Node Dissection Necessary in All Patients with Ductal Carcinoma In Situ Undergoing Total Mastectomy?

    PubMed

    Bonev, Valentina; De Paz Villanueva, Carlos Chavez; Solomon, Naveenraj; Senthil, Maheswari; Reeves, Mark E; Garberoglio, Carlos; Lum, Sharon S

    2016-10-01

    When ductal carcinoma in situ (DCIS) is found on core needle biopsy, rates of upgrade to invasive cancer of 25 per cent and nodal positivity of 10 per cent have been reported. Sentinel lymph node dissection (SLND) is recommended when mastectomy is performed for DCIS. We investigated the role of SLND in DCIS patients undergoing partial and total mastectomy (TM). During the study period 2004 to 2013, 170 patients with DCIS were identified with a median age of 60 years (range 26-84 years). Of these, 58.2 per cent had partial mastectomy (PM) alone, 10.6 per cent had PM with SLND, and 31.1 per cent had TM with or without contralateral prophylactic mastectomy with SLND. Overall, SLND identified positive nodes in 4.2 per cent of patients. Upgrade to invasive carcinoma on final breast pathology was found in 8.2 per cent of patients overall, including 4.0 per cent of patients undergoing PM alone, 22.2 per cent undergoing PM with SLND, and 11.3 per cent for TM with SLND (P = 0.8). In this study, patients diagnosed with DCIS on core needle biopsy had lower than expected rates of positive sentinel nodes and upgrade to invasive carcinoma. Surgeons and patients should revisit the necessity of SLND in DCIS patients undergoing mastectomy, which could lead to decreased health expenditure, resources, time, morbidity, and emotional impact on patients.

  7. Overview of the Randomized Trials of Radiotherapy in Ductal Carcinoma In Situ of the Breast

    PubMed Central

    2010-01-01

    Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality. PMID:20956824

  8. Identifying three different architectural subtypes of mammary ductal carcinoma in situ using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, shuangmu; Wang, Chuan; Chen, Jianxin

    2015-10-01

    Ductal carcinoma in situ (DCIS) is often considered as the precursor of invasive breast cancer, and the risk of DCIS progression to IBC has been estimated based on the evaluation of pathological features, among which the architectural subtype is the most common one. In this study, multiphoton microscopy (MPM) is applied to identify three different architectural subtypes of DCIS (solid, cribriform and comedo). It is found that MPM has the capability to visualize the proliferating pattern of tumor cells, the presence of intraluminal necrosis and the morphology of basement membrane, which are all taken into account in subtyping DCIS. In addition, MPM also can be used to quantify the cellular metabolism, for quantitatively identifying tumor staging during tumor progression. This result highlights the potential of MPM as an advanced technique to assess the pathological characters of the breast tumor in real-time and reflect the degree of tumor progression in vivo, by integrating into the intra-fiberoptic ductoscopy or transdermal biopsy needle.

  9. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast

    PubMed Central

    Cao, Shui; Kang, Hong-Gang; Liu, Yan-Xue; Ren, Xiu-Bao

    2009-01-01

    Background Extramedullary plasmacytomas are seldom solitary and usually progress to diffuse myelomatosis. Plasmacytomas of the breast are rare, especially when not associated multiple myeloma. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast have not previously reported. Case presentation A 27-years-old woman with an untreated upper outer quadrant breast mass for 1-year was referred to our cancer hospital for surgical evaluation of increasing breast pain. Postoperatively, microscopic examination revealed an infiltrating ductal carcinoma complicated by an extramedullary plasmacytoma divided by fibrous tissue in one section. Following surgery, the patient received chemotherapy for the carcinoma and radiotherapy for the plasmacytoma. Conclusion In this case, careful histopathology examination was essential to make the correct diagnosis and therapy for these synchronous lesions. The patient finished chemotherapy and radiotherapy without significant adverse effects. PMID:19393076

  10. Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival.

    PubMed

    Kuba, Sayaka; Ohtani, Hiroshi; Yamaguchi, Junzo; Hayashi, Hiroko; Uga, Tatsuya; Kanematsu, Takashi; Shimokawa, Isao

    2011-02-01

    Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast.

  11. [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

    Antecedentes: en pacientes con carcinoma ductal in situ la biopsia de ganglio centinela es motivo de controversia porque se reportan ganglios positivos en 1.4-12.5% debido al carcinoma invasor oculto en la pieza quirúrgica. Objetivo: conocer la frecuencia de metástasis en ganglio centinela en pacientes con carcinoma ductal in situ e identificar las diferencias entre los casos positivos y negativos. Material y métodos: estudio retrospectivo, transversal, analítico de pacientes con carcinoma ductal in situ a quienes se realizó una biopsia de ganglio centinela por requerir mastectomía, tener un tumor palpable, lesión radiológica = 5 cm, inadecuada relación mama-tumor o porque la escisión pudiera afectar el flujo linfático. Resultados: de 168 carcinomas in situ, se incluyeron 50 casos con carcinoma ductal in situ y biopsia de ganglio centinela, de pacientes con edad promedio de 51.6 años, 30 (60%) de ellas asintomáticas. Los signos reportados fueron: nódulo palpable (18%), secreción por el pezón (12%) o ambos (8%). Predominaron las microcalcificaciones (72%), comedonecrosis (62%) y grado histológico -2 (44%) con 28% de receptores hormonales negativos. En el estudio transoperatorio 4 (8%) pacientes tuvieron ganglio centinela positivo y un caso en estudio histopatológico definitivo (60% micrometástasis, 40% macrometástasis), todos con carcinoma invasor en la pieza quirúrgica. Las pacientes con ganglio centinela transoperatorio positivo eran más jóvenes (44.5 vs 51 años), con más tumores palpables (50 vs 23.1%), más grandes (3.5 vs 2 cm), más comedonecrosis (75 vs 60.8%), más indiferenciados (75% vs 39.1%) y menos receptores hormonales (50 vs 73.9%), que las que tenían ganglio centinela negativo, sin que estas diferencias tuvieran significación estadística. Conclusiones: puesto que 1 de cada 12 pacientes con carcinoma ductal in situ tiene afectación ganglionar en el ganglio centinela, se recomienda seguir tomando la biopsia para evitar

  12. Immunohistochemical localisation of pS2 protein in ductal carcinoma in situ and benign lesions of the breast.

    PubMed Central

    Luqmani, Y. A.; Campbell, T.; Soomro, S.; Shousha, S.; Rio, M. C.; Coombes, R. C.

    1993-01-01

    The expression of pS2 was examined histochemically in paraffin sections taken from biopsy material from patients diagnosed with ductal carcinoma in situ (DCIS). Often intense immunoreactivity, to an anti-pS2 monoclonal antibody, was observed in comedo, solid, cribriform and micropapillary types of DCIS, with significant positivity found in 63-67% of cases. In 15 samples analysed, we found a good correlation between pS2 expression and presence of progesterone receptor positive cells, but not with estrogen receptor. There was only a limited degree of correspondence between the cells staining with these anti-sera. Some pS2 positive cells were also seen in normal acini in areas adjacent to cancer but much less frequently in sections of normal breast from reduction mammoplasty. Most normal areas were negative, as were cysts. In benign proliferative conditions (seen in sections with and without DCIS) such as adenosis, sclerosing adenosis, mild and florid ductal epithelial hyperplasia, significant pS2 positivity was seen in about 50% of cases. These results suggest that there is a progressive increase in pS2 from normal to benign to cancer cells and that this gene is expressed in both the invasive and pre-invasive forms of breast cancer. Images Figure 1 Figure 2 Figure 3 PMID:8385977

  13. Predictive Factors for BRCA1/BRCA2 Mutations in Women With Ductal Carcinoma In Situ

    PubMed Central

    Bayraktar, Soley; Elsayegh, Nisreen; Gutierrez Barrera, Angelica M.; Lin, Heather; Kuerer, Henry; Tasbas, Tunc; Muse, Kimberly I.; Ready, Kaylene; Litton, Jennifer; Meric-Bernstam, Funda; Hortobagyi, Gabriel N.; Albarracin, Constance T.; Arun, Banu

    2015-01-01

    Background It is unclear whether women with ductal carcinoma in situ (DCIS), like their counterparts with invasive breast cancer, warrant genetic risk assessment and testing on the basis of high-risk variables. The authors of this report identified predictive factors for mutations in the breast cancer-susceptibility genes BRCA1 and BRCA2 in women who were diagnosed with DCIS. Methods One hundred eighteen women with DCIS who were referred for genetic counseling and underwent genetic testing for BRCA1/BRCA2 mutations between 2003 and 2010 were included in the study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. Results Of 118 high-risk women with DCIS, 27% (n = 32) tested positive for BRCA1/BRCA2 mutations. Of those, 10% (n = 12) and 17% (n = 20) had BRCA1 and BRCA2 mutations, respectively. Age, race, and tumor characteristics did not differ between BRCA noncarriers and carriers. In a multivariate logistic model, ≥2 relatives with ovarian cancer (OC) (odds ratio [OR], 8.81; 95% confidence interval [CI], 1.38-56.29; P = .034), and a score ≥10% according to the BRCAPRO mathematical model for calculating the probability that a particular family member carries a germline BRCA mutation (OR, 6.37; 95% CI, 2.23-18.22; P = .0005) remained as independent significant predictors for a BRCA mutation. Fifty-seven percent of mutation carriers but only 25% of noncarriers underwent prophylactic mastectomy (P = .0037). This difference remained significant for patients aged ≤40 years (P = .025). Conclusions Women who had DCIS and a family history of OC or who had BRCAPRO scores ≥10% had a high rate of BRCA positivity regardless of age at diagnosis. These findings suggest that high-risk patients with DCIS are appropriate candidates for genetic testing for BRCA mutations in the presence of predictive factors even if they do not have invasive breast cancer. PMID:22009639

  14. Five Year Outcome of 145 Patients With Ductal Carcinoma In Situ (DCIS) After Accelerated Breast Radiotherapy

    SciTech Connect

    Ciervide, Raquel; Dhage, Shubhada; Guth, Amber; Shapiro, Richard L.; Axelrod, Deborah M.; Roses, Daniel F.; Formenti, Silvia C.

    2012-06-01

    Background: Accelerated whole-breast radiotherapy (RT) with tumor bed boost in the treatment of early invasive breast cancer has demonstrated equivalent local control and cosmesis when compared with standard RT. Its efficacy in the treatment of ductal carcinoma in situ (DCIS) remains unknown. Methods and Materials: Patients treated for DCIS with lumpectomy and negative margins were eligible for 2 consecutive hypofractionated whole-breast RT clinical trials. The first trial (New York University [NYU] 01-51) prescribed to the whole breast 42 Gy (2.8 Gy in 15 fractions) and the second trial (NYU 05-181) 40.5 Gy (2.7 Gy in 15 fractions) with an additional daily boost of 0.5 Gy to the surgical cavity. Results: Between 2002 and 2009, 145 DCIS patients accrued, 59 to the first protocol and 86 to the second trial. Median age was 56 years and 65% were postmenopausal at the time of treatment. Based on optimal sparing of normal tissue, 79% of the patients were planned and treated prone and 21% supine. At 5 years' median follow-up (60 months; range 2.6-105.5 months), 6 patients (4.1%) experienced an ipsilateral breast recurrence in all cases of DCIS histology. In 3/6 patients, recurrence occurred at the original site of DCIS and in the remaining 3 cases outside the original tumor bed. New contralateral breast cancers arose in 3 cases (1 DCIS and 2 invasive carcinomas). Cosmetic self-assessment at least 2 years after treatment is available in 125 patients: 91% reported good-to-excellent and 9% reported fair-to-poor outcomes. Conclusions: With a median follow-up of 5 years, the ipsilateral local recurrence rate is 4.1%, comparable to that reported from the NSABP (National Surgical Adjuvant Breast and Bowel Project) trials that employed 50 Gy in 25 fractions of radiotherapy for DCIS. There were no invasive recurrences. These results provide preliminary evidence that accelerated hypofractionated external beam radiotherapy is a viable option for DCIS.

  15. Regulation of in situ to invasive breast carcinoma transition

    SciTech Connect

    Polyak, Kornelia; Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen, Haiyan; Carrasco, Daniel; Richardson, Andrea; Violette, Shelia; Gelman, Rebecca S.; Bissell, Mina J.; Schnitt, Stuart; Polyak, Kornelia

    2008-05-07

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  16. Regulation of In Situ to Invasive Breast CarcinomaTransition

    SciTech Connect

    Hu, Min; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen,Haiyan; Carrasco, Daniel; Richardson, Andrea; Bissell, Mina; Violette,Shelia; Gelman, Rebecca S.; Schnitt, Stuart; Polyak, Kornelia

    2007-03-13

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  17. Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

    ClinicalTrials.gov

    2017-04-14

    Ductal Breast Carcinoma In Situ; Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Invasive Breast Carcinoma; Multicentric Breast Carcinoma; Multifocal Breast Carcinoma; Synchronous Bilateral Breast Carcinoma

  18. Association Between Patient and Tumor Characteristics With Clinical Outcomes in Women With Ductal Carcinoma In Situ

    PubMed Central

    Wang, Shi-Yi; Virnig, Beth A.; Tuttle, Todd M.; Kane, Robert L.

    2010-01-01

    We synthesized the evidence of the association between patient and tumor characteristics with clinical outcomes in women with ductal carcinoma in situ of the breast. We identified five randomized controlled clinical trials and 64 observational studies that were published in English from January 1970 to January 2009. Younger women with clinically presented ductal carcinoma in situ had higher risk of ipsilateral recurrent cancer. African Americans had higher mortality and greater rates of advanced recurrent cancer. Women with larger tumor size, comedo necrosis, worse pathological grading, positive surgical margins, and at a higher risk category, using a composite prognostic index, had worse outcomes. Inconsistent evidence suggested that positive HER2 receptor and negative estrogen receptor status were associated with worse outcomes. Synthesis of evidence was hampered by low statistical power to detect significant differences in predictor categories and inconsistent adjustment practices across the studies. Future research should address composite prediction indices among race groups for all outcomes. PMID:20956815

  19. Sarcomatoid carcinoma of the prostate: ductal adenocarcinoma and stromal sarcoma-like appearance: a rare association.

    PubMed

    Parada, David; Peña, Karla B; Riu, Francesc

    2011-01-01

    Sarcomatoid carcinoma (SC) of prostate gland is a rare biphasic tumour. In about half of cases, initial diagnosis is acinar adenocarcinoma, followed by nonsurgical therapy, with a subsequent diagnosis of SC. The survival rate is lower. We report a case of an 59-years-old man with unusual histopathologic finding of prostate sarcomatoid carcinoma, showing characteristics of ductal prostatic adenocarcinoma and prostatic stromal sarcoma-like appearance. Ductal adenocarcinoma was characterized by tall columnar cells with abundant amphophilic to eosinophil cytoplasm. Pleomorphic sarcoma was characterized to have overall glandular growth pattern, simulating a malignant phyllodes tumour. Estrogen and progesterone receptors showed nuclear immunostaining in mesenchymal multinucleated giant cells. In conclusion, SC of the prostate is an exceedingly rare tumour. Retrospective analyses render prostate SC as one of the most aggressive prostate malignancies. The prognosis is dismal regardless of other histologic or clinical findings.

  20. Digital mammography screening: association between detection rate and nuclear grade of ductal carcinoma in situ.

    PubMed

    Weigel, Stefanie; Heindel, Walter; Heidinger, Oliver; Berkemeyer, Shoma; Hense, Hans Werner

    2014-04-01

    To determine the relationship between overall detection rates of ductal carcinoma in situ (DCIS) and the specific detection rates of low-, intermediate-, and high-grade DCIS at the start of a digital mammography screening program. The study was approved by the local ethics board and did not require informed consent. Data were included of the first round of digital mammography examinations, performed in 17 screening units in women aged 50-69 years from 2005 to 2008. Grading was provided by the cancer registry for 1018 DCIS cases. The association between the overall cancer detection rate (cases per 100 women screened) and the separate cancer detection rate for invasive cancers and for DCIS was assessed. Likewise, the total DCIS cancer detection rate was separated into rates for low, intermediate, and high grades. Spearman rank correlations were used for analysis. The overall cancer detection rate correlated with both the cancer detection rate of invasive cancers and the cancer detection rate of DCIS (r = 0.96 and r = 0.88, respectively; P < .001 for both). The cancer detection rate of total DCIS with grading varied among screening units (range, 0.05-0.25), it was borderline not significantly correlated with the cancer detection rate of low-grade DCIS (range, 0.004-0.05; r = 0.49; P = .052), and it showed significant correlations with higher cancer detection rate of intermediate-grade DCIS (range, 0.02-0.12; r = 0.89; P < .001) and of high-grade DCIS (range, 0.03-0.11; r = 0.88; P < .001). This study demonstrates that high overall cancer detection rates in digital mammography screening are related to high detection rates of invasive cancers, as well as DCIS. Increases in the detection rates of DCIS were not driven by disproportionate increments of the slowly progressive low-grade subtype but rather by increased rates of intermediate- and high-grade subtypes that carry a higher risk of transition to invasive cancers. RSNA, 2013

  1. Treatment of ductal carcinoma in situ of the breast: review of recent advances and future prospects.

    PubMed

    Mokbel, Kefah

    2003-01-01

    Ductal carcinoma in situ (DCIS) is a heterogeneous disease characterized by noninvasive clonal proliferation of malignant epithelial cells arising from the mammary ducts and terminal ductal-lobular units. Its reported incidence is rising due to the wide adoption of screening mammography. The combination of nuclear grade and presence of necrosis is currently the best predictor of biological behavior. Approximately 25-50% of DCIS lesions progress to invasive disease if left untreated. The treatment options for DCIS include total mastectomy with or without immediate breast reconstruction (IBR), local excision (LE) plus adjuvant radiotherapy (RT), and LE alone. Total mastectomy is associated with lowest rates of local recurrence and breast cancer-specific mortality. If IBR is considered, then skin-sparing mastectomy (SSM) combined with autologous myocutaneous flap reconstruction can achieve excellent cosmesis without compromising local control. The role of adjuvant radiotherapy (RT) after LE remains controversial. Three recent randomized controlled trials have demonstrated that adjuvant RT after LE of localized DCIS significantly reduces the incidence of local recurrence. However, these trials did not identify any subgroups of patients where RT could be safely omitted and were criticized for lack of emphasis on standardized and meticulous tissue processing and pathological evaluation. Retrospective studies indicate that RT can be safely omitted after adequate LE (margin width > or = 1 cm) of small (< 15 mm), non-high grade DCIS not associated with necrosis. The role of tamoxifen in the treatment of DCIS continues to evolve. Formal axillary dissection is not appropriate for DCIS; however, the potential role of the sentinel node biopsy (SNB) in selected high-risk cases requires further evaluation. Areas of ongoing and future research include the potential role of third-generation aromatase inhibitors and third- and fourth-generation selective estrogen receptor modulators

  2. Comparison of Local Recurrence After Simple and Skin-Sparing Mastectomy Performed in Patients with Ductal Carcinoma In Situ.

    PubMed

    Timbrell, Simon; Al-Himdani, Sarah; Shaw, Oliver; Tan, Kian; Morris, Julie; Bundred, Nigel

    2017-04-01

    The incidence of ductal carcinoma in situ (DCIS) is increasing with the use of screening mammography, and approximately 30% of all women diagnosed with DCIS are treated by mastectomy. There is increasing use of a skin-sparing mastectomy (SSM) approach to surgically excise DCIS as this facilitates immediate breast reconstruction. The rates of locoregional recurrence (LRR) after simple mastectomy performed for pure DCIS are historically reported as 1%; however, international data suggest that LRR after SSM may be higher. To determine our rates of LRR and compare the effect of the type of mastectomy performed, we undertook a retrospective review of all patients who underwent a mastectomy for pure DCIS at our institution between 2000 and 2010. In total, 199 patients underwent a mastectomy for pure DCIS (with eight local recurrences), all of which were invasive ductal carcinoma. The recurrences all occurred after SSM, which was associated with a higher 5-year LRR of 5.9% (5/102) compared with 0% in the simple mastectomy group (0/97; p = 0.012), log-rank. Univariate analysis showed the two factors that predicted the risk of recurrence were a young age at mastectomy and close or involved margins. These data highlight the importance of achieving clear margins, especially in young women with estrogen receptor-negative DCIS who have a higher risk of invasive recurrence. Women undergoing a mastectomy for DCIS should be counseled as to the importance of achieving clear margins and the potential increased need for further excision, post-mastectomy radiotherapy and post-reconstruction mammography in order to prevent LRR after SSM.

  3. The role of specimen radiography in breast-conserving therapy of ductal carcinoma in situ.

    PubMed

    Lange, M; Reimer, T; Hartmann, S; Glass, Ä; Stachs, A

    2016-04-01

    To assess the role of intraoperative specimen radiography (SR) and to define risk factors for positive margins in breast-conserving therapy (BCT) of ductal carcinoma in situ (DCIS). In a retrospective study in calcification-associated DCIS treated with BCT between January 2009 and December 2011, digital mammographs and SR were reviewed and radiological margin width was determined. Clinical, radiological, and histological data were correlated with surgical histological data, and a histologically free margin of at least 2 mm was taken as evidence of successful BCT. 47/91 patients (51.6%) fulfilling the inclusion criteria had histologically involved surgical margins. Univariate analyses revealed DCIS size, mammographic extension of calcification, presence of comedo necrosis, negative progesterone receptor status, and a small radiological margin on SR to be risk factors for unsuccessful BCT. Receiver Operating Characteristic (ROC) analysis showed a radiological margin width of 4 mm to be optimal, with a sensitivity of 72.3% and specificity of 52.3%. The likelihood of surgical free margins was increased 2.9-fold with a radiological margin width ≥4 mm. On multivariate logistic regression analysis, only histological DCIS size >20 mm clearly emerged as an independent predictive factor for surgically involved margins (p < 0.001), while an SR margin <4 mm trended toward significance (p = 0.066). SR is a reliable method for predicting free surgical margins in non-invasive breast cancer where a minimum radiological free margin of 4 Fmm is achieved. However, histological DCIS size remains the most important factor determining successful BCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Towards optimal management of ductal carcinoma in situ of the breast.

    PubMed

    Mokbel, Kefah

    2003-03-01

    Ductal carcinoma in situ (DCIS) represents a spectrum of heterogenous disease that accounts for approximately one fifth of all screen-detected breast cancers and is considered as a precursor of invasive breast cancer if left untreated (35-50% risk). DCIS can be treated by total mastectomy with or without immediate breast reconstruction, local excision (LE) plus adjuvant radiotherapy (RT) or LE alone. Total mastectomy is associated with low rates of local recurrence (1.4%) and breast cancer-specific mortality (0.59%). Three recent randomized controlled trials (RCTs) have demonstrated that adjuvant RT after LE of localized DCIS significantly reduces the incidence of local recurrence. However these trials did not identify any subgroups of patients where RT could be safely omitted. Retrospective studies suggest that RT can be safely omitted after adequate LE (margin width > or =1 cm) of small (< 15 mm), non-high grade DCIS not associated with necrosis. Further RCTs are required to validate these retrospective findings, with an emphasis on standardized and meticulous tissue processing and pathological evaluation. The role of adjuvant tamoxifen in the management of DCIS continues to evolve. Formal axillary dissection is not appropriate for DCIS, however, the potential role of the sentinel node biopsy (SNB) in selected high risk cases requires further evaluation. The International Breast Cancer Intervention Study (IBIS-II) trial aims to evaluate the potential role of third generation aromatase inhibitors in postmenopausal women with hormone-sensitive DCIS.Future research will focus on the relevance of gene expression profiling, proteomics, Laser therapy and mammary ductoscopy to the management of DCIS.

  5. Impact of Margin Status on Local Recurrence After Mastectomy for Ductal Carcinoma In Situ

    SciTech Connect

    Childs, Stephanie K.; Chen, Yu-Hui; Duggan, Margaret M.; Golshan, Mehra; Pochebit, Stephen; Punglia, Rinaa S.; Wong, Julia S.; Bellon, Jennifer R.

    2013-03-15

    Purpose: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy. Methods and Materials: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy. Results: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence. Conclusions: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted.

  6. Patient-reported outcomes in ductal carcinoma in situ: A systematic review.

    PubMed

    King, Madeleine T; Winters, Zoë E; Olivotto, Ivo A; Spillane, Andrew J; Chua, Boon H; Saunders, Christobel; Westenberg, A Helen; Mann, G Bruce; Burnett, Petrina; Butow, Phyllis; Rutherford, Claudia

    2017-01-01

    Ductal carcinoma in situ (DCIS) is a pre-invasive breast cancer with excellent prognosis but with potential adverse impacts of diagnosis and treatment on quality of life and other patient-reported outcomes (PROs). We undertook a systematic review to synthesise current evidence about PROs following diagnosis and treatment for DCIS. We searched five electronic databases (from database inception to November 2015), cross-referenced and contacted experts to identify studies that reported PROs after DCIS treatment. Two reviewers independently applied inclusion and quality criteria, and extracted findings. Of 2130 papers screened, 23 were eligible, reporting 17 studies. Short- and long-term PRO evidence about differences between DCIS treatment options was lacking. Evidence pooled across treatments indicated core aspects of quality of life (physical, role, social, emotional function, pain, fatigue) and psychological distress (anxiety, depression) were impacted significantly initially, with most aspects returning to population norms by 6-12 months, and all by 2 years post-operatively. Fears of recurrence and dying from breast cancer were exaggerated, occurred early and persisted for many years. Sexuality and body image impacts were generally low and resolved within 1-3 months after surgery. A minority of women experienced considerable impact, including depression and sexual issues associated with body image problems. Well-powered PRO studies are required to track recovery trajectories and long-term impacts of the range of contemporary and emerging local and systemic treatments for DCIS. PRO data would enable care providers to prepare patients for short-term sequelae and enable patients who have treatment options to exercise preferences in choosing among them.

  7. Outcomes in Patients Treated With Mastectomy for Ductal Carcinoma In Situ

    SciTech Connect

    Owen, Dawn; Tyldesley, Scott; Alexander, Cheryl; Speers, Caroline; Truong, Pauline; Nichol, Alan; Wai, Elaine S.

    2013-03-01

    Purpose: To examine, in a large, population-based cohort of women, the risk factors for recurrence after mastectomy for pure ductal carcinoma in situ (DCIS) and to identify which patients may benefit from postmastectomy radiation therapy. Methods and Materials: Data were analyzed for 637 subjects with pure DCIS, diagnosed between January 1990 and December 1999, treated initially with mastectomy. Locoregional relapse (LRR), breast cancer-specific survival, and overall survival were described using the Kaplan-Meier method. Reported risk factors for LRR (age, margins, size, Van Nuys Prognostic Index, grade, necrosis, and histologic subtype) were analyzed by univariate (log-rank) and multivariate (Cox modeling) methods. Results: Median follow-up was 12.0 years. Characteristics of the cohort were median age 55 years, 8.6% aged ≤40 years, 30.5% tumors >4 cm, 42.5% grade 3 histology, 37.7% multifocal disease, and 4.9% positive margins. At 10 years, LRR was 1.0%, breast cancer-specific survival was 98.0%, and overall survival was 90.3%. All recurrences (n=12) involved ipsilateral chest wall disease, with the majority being invasive disease (11 of 12). None of the 12 patients with recurrence died of breast cancer; all were successfully salvaged (median follow-up of 4.4 years). Ten-year LRR was higher with age ≤40 years (7.5% vs 1.5%; P=.003). Conclusion: Mastectomy provides excellent locoregional control for DCIS. Routine use of postmastectomy radiation therapy is not justified. Young age (≤40 years) predicts slightly higher LRR, but possibly owing to the small number of cases with multiple risk factors for relapse, a subgroup with a high risk of LRR (ie, approximately 15%) was not identified.

  8. Cytopathological grading, as a predictor of histopathological grade, in ductal carcinoma (NOS) of breast, on air-dried Diff-Quik smears.

    PubMed

    Khan, M Z; Haleem, A; Al Hassani, H; Kfoury, H

    2003-10-01

    Fine-needle aspiration cytology (FNAC) is a widely practiced technique in the diagnosis of breast carcinoma, and it is the only diagnostic procedure performed before definitive treatment, at most institutions. While the histological grading of breast carcinoma has become routine in many centers worldwide, the cytopathological grading of breast carcinoma is not commonly used. Grading of breast carcinoma, while the tumor is still in vivo, would be the most ideal and desirable situation, as it would be helpful in the selection of patients for appropriate therapy. The objective of this study, therefore, was to devise a simple system for grading breast carcinoma, based on the cytological features alone. We reviewed 125 cases of breast carcinoma retrospectively, which were initially diagnosed by FNAC, with subsequent histopathological confirmation. These included 105 ductal, 6 lobular, 2 tubular, 1 papillary, and 1 medullary carcinoma. There was 1 ductal carcinoma in situ. Nine cases were rendered insufficient for grading. Thus 105 cases of ductal carcinoma (NOS) were evaluated for final cytological grading. Air-dried Diff-Quik-stained smears were reviewed at least twice independently by four histopathologists and were then compared with the original histological grades. Six cytological features used for grading were found to be statistically significant: cellular pleomorphism, nuclear size, nuclear margin, nucleoli, naked tumor nuclei, and mitoses. A scoring system based on these six essential parameters was used, to classify ductal carcinoma into three cytological grades, which showed close correlation with the established histological grades. In addition, two less consistent, but still important, features were the presence or absence of necrosis and stromal invasion. Another six parameters, including smear cellularity, degree of cell dispersion or clustering, lymphoplasmacytic infiltrate, presence of tubular structures, cytoplasmic appearance of the tumor cells, and

  9. Telomere length alterations unique to invasive lobular carcinoma.

    PubMed

    Heaphy, Christopher M; Asch-Kendrick, Rebecca; Argani, Pedram; Meeker, Alan K; Cimino-Mathews, Ashley

    2015-08-01

    Telomeres are nucleoprotein complexes located at the extreme ends of eukaryotic chromosomes and protect chromosomal ends from degradation and recombination. Dysfunctional telomeres contribute to genomic instability, promote tumorigenesis, and, in breast cancer, have been associated with increased cancer risk and poor prognosis. Short telomere lengths have been previously associated with triple-negative and human epidermal growth factor receptor (Her2)--positive ductal carcinomas. However, these investigations have not specifically assessed invasive lobular carcinomas (ILCs), which accounts for 5% to 15% of all invasive breast cancers. Here, we evaluate telomere lengths within 48 primary ILCs with complete characterization of estrogen receptor (ER), progesterone receptor (PR), and Her2 status, including 32 luminal/Her2- (ER+/PR+/Her2-), 8 luminal/Her2+ (ER+/PR+/Her2+), 3 Her2+ (ER-/PR-/Her2+), and 5 triple-negative (ER-/PR-/Her2-) carcinomas. A telomere-specific fluorescence in situ hybridization assay, which provides single-cell telomere length resolution, was used to evaluate telomere lengths and compare with standard clinicopathological markers. In contrast to breast ductal carcinoma, in which more than 85% of cases display abnormally short telomeres, approximately half (52%) of the ILCs displayed either normal or long telomeres. Short telomere length was associated with older patient age. Interestingly, 3 cases (6%) displayed a unique telomere pattern consisting of 1 or 2 bright telomere spots among the normal telomere signals within each individual cancer cell, a phenotype that has not been previously described. Additional studies are needed to further evaluate the significance of the unique bright telomere spot phenotype and the potential utility of telomere length as a prognostic marker in ILC.

  10. Pleomorphic ductal carcinoma of the breast with predominant micropapillary features.

    PubMed

    Lenicek, Tanja; Szerda, Ferenc; Demirović, Alma; Mijić, August; Kruslin, Bozo; Tomas, Davor

    2007-10-01

    An 83-year-old woman with long-standing chronic ischemic cardiac and obstructive pulmonary disease, presented with a painless tumor in her right breast. Microscopically the tumor consisted of micropapillary formations and loosely cohesive nests and strands of large, highly pleomorphic cells. Micropapillary formations were surrounded by peritumoral retraction clefting, and the papillae lacked a true fibrovascular core. Multinucleated giant and bizarre tumor cells were also present and numerous. Within the tumor a high-grade intraductal component with the same cell morphology and necrosis and mucin production was found. Micropapillary pattern occupied approximately 60% of the tumor mass, loosely cohesive nests and strands approximately 20% and an intraductal component was noted in approximately 20% of the tumor mass. On immunohistochemistry the tumor cells were positive for pan-cytokeratin, epithelial membrane antigen (EMA), S100 protein and E-cadherin while estrogen and progesterone receptors, HER2-neu and Bcl2 were negative. EMA staining was diffuse and observed in the outer and inner margins of neoplastic nests. The diagnosis of pleomorphic breast carcinoma with predominant micropapillary features was established. In summary, micropapillary carcinoma can be distinguished from other types of breast carcinoma with micropapillary growth pattern on the basis of reverse cell polarity, which is easily confirmed on immunohistochemistry.

  11. Total pancreatectomy for metachronous mixed acinar-ductal carcinoma in a remnant pancreas.

    PubMed

    Shonaka, Tatsuya; Inagaki, Mitsuhiro; Akabane, Hiromitsu; Yanagida, Naoyuki; Shomura, Hiroki; Yanagawa, Nobuyuki; Oikawa, Kensuke; Nakano, Shiro

    2014-09-07

    In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct. Mucin5AC, α1-antitrypsin (α-AT) and carcinoembryonic antigen (CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.

  12. Results of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS).

    PubMed

    Fowble, B; Hanlon, A L; Fein, D A; Hoffman, J P; Sigurdson, E R; Patchefsky, A; Kessler, H

    1997-07-15

    The role of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS) is controversial. In particular, there is little data for outcome with radiation in a group of patients comparable to those treated with local excision and surveillance (mammographic calcifications < or = 2.5 cm, negative resection margins, negative postbiopsy mammogram). This study reports outcome of conservative surgery and radiation for mammographically detected DCIS with an emphasis on results in patients considered candidates for excision alone. From 1983 to 1992, 110 women with mammographically detected DCIS (77% calcifications +/- mass) and no prior history of breast cancer underwent needle localization and biopsy with (55%) or without a reexcision and radiation. Final margins of resection were negative in 62%, positive 7%, close 11%, and unknown 20%. The median patient age was 56 years. The most common histologic subtype was comedo (54%), followed by cribriform (22%). The median pathologic tumor size was 8 mm (range 2 mm to 5 cm). Forty-seven percent of patients with calcifications only had a negative postbiopsy mammogram prior to radiation. Radiation consisted of treatment to the entire breast (median 50.00 Gy) and a boost to the primary site (97%) for a median total dose of 60.40 Gy. With a median follow-up of 5.3 years, three patients developed a recurrence in the treated breast. The median interval to recurrence was 8.8 years and all were invasive cancers. Two (67%) occurred outside the initial quadrant. The 5- and 10-year actuarial rates of recurrence were 1 and 15%. Cause-specific survival was 100% at 5 and 10 years. Contralateral breast cancer developed in two patients. There were too few failures for statistical significance to be achieved with any of the following factors: patient age, family history, race, mammographic findings, location primary, pathologic size, histologic subtype, reexcision, or final margin status. However, young age

  13. Detection of ductal carcinoma in situ in women undergoing screening mammography.

    PubMed

    Ernster, Virginia L; Ballard-Barbash, Rachel; Barlow, William E; Zheng, Yingye; Weaver, Donald L; Cutter, Gary; Yankaskas, Bonnie C; Rosenberg, Robert; Carney, Patricia A; Kerlikowske, Karla; Taplin, Stephen H; Urban, Nicole; Geller, Berta M

    2002-10-16

    With the large number of women having mammography-an estimated 28.4 million U.S. women aged 40 years and older in 1998-the percentage of cancers detected as ductal carcinoma in situ (DCIS), which has an uncertain prognosis, has increased. We pooled data from seven regional mammography registries to determine the percentage of mammographically detected cancers that are DCIS and the rate of DCIS per 1000 mammograms. We analyzed data on 653 833 mammograms from 540 738 women between 40 and 84 years of age who underwent screening mammography at facilities participating in the National Cancer Institute's Breast Cancer Surveillance Consortium (BCSC) throughout 1996 and 1997. Mammography results were linked to population-based cancer and pathology registries. We calculated the percentage of screen-detected breast cancers that were DCIS, the rate of screen-detected DCIS per 1000 mammograms by age and by previous mammography status, and the sensitivity of screening mammography. Statistical tests were two-sided. A total of 3266 cases of breast cancer were identified, 591 DCIS and 2675 invasive breast cancer. The percentage of screen-detected breast cancers that were DCIS decreased with age (from 28.2% [95% confidence interval (CI) = 23.9% to 32.5%] for women aged 40-49 years to 16.0% [95% CI = 13.3% to 18.7%] for women aged 70-84 years). However, the rate of screen-detected DCIS cases per 1000 mammograms increased with age (from 0.56 [95% CI = 0.41 to 0.70] for women aged 40-49 years to 1.07 [95% CI = 0.87 to 1.27] for women aged 70-84 years). Sensitivity of screening mammography in all age groups combined was higher for detecting DCIS (86.0% [95% CI = 83.2% to 88.8%]) than it was for detecting invasive breast cancer (75.1% [95% CI = 73.5% to 76.8%]). Overall, approximately 1 in every 1300 screening mammography examinations leads to a diagnosis of DCIS. Given uncertainty about the natural history of DCIS, the clinical significance of screen-detected DCIS needs further

  14. Second primary pancreatic ductal carcinoma in the remnant pancreas after pancreatectomy for pancreatic ductal carcinoma: High cumulative incidence rates at 5 years after pancreatectomy.

    PubMed

    Ishida, Jun; Toyama, Hirochika; Matsumoto, Ippei; Asari, Sadaki; Goto, Tadahiro; Terai, Sachio; Nanno, Yoshihide; Yamashita, Azusa; Mizumoto, Takuya; Ueda, Yuki; Kido, Masahiro; Ajiki, Tetsuo; Fukumoto, Takumi; Ku, Yonson

    2016-01-01

    The aim of this study was to determine the incidence rate and clinical features of second primary pancreatic ductal carcinoma (SPPDC) in the remnant pancreas after pancreatectomy for pancreatic ductal carcinoma (PDC). Data of patients undergoing R0 resection for PDC at a single high-volume center were reviewed. SPPDC was defined as a tumor in the remnant pancreas after R0 resection for PDC, and SPPDC met at least one of the following conditions: 1) the time interval between initial pancreatectomy and development of a new tumor was 3 years or more; 2) the new tumor was not located in contact with the pancreatic stump. We investigated the clinical features and treatment outcomes of patients with SPPDC. This study included 130 patients who underwent surgical resection for PDC between 2005 and 2014. Six (4.6%) patients developed SPPDC. The cumulative 3- and 5-year incidence rates were 3.1% and 17.7%, respectively. Four patients underwent remnant pancreatectomy for SPPDC. They were diagnosed with the disease in stage IIA or higher and developed recurrence within 6 months after remnant pancreatectomy. One patient received carbon ion radiotherapy and survived 45 months. One patient refused treatment and died 19 months after the diagnosis of SPPDC. The incidence rate of SPPDC is not negligible, and the cumulative 5-year incidence rate of SPPDC is markedly high. Post-operative surveillance of the remnant pancreas is critical for the early detection of SPPDC, even in long-term survivors after PDC resection. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  15. Prognostic Significance of Telomere Attrition in Ductal Carcinoma in situ of the Breast

    DTIC Science & Technology

    2009-02-01

    Burstein, HJ, Polyak , K, Wong, JS, Lester, SC and Kaelin, CM. Ductal Carcinoma in Situ of the Breast. N Engl J Med 350:1430-41, 2004. 4. Page DL, Dupont...nodeT a b le 1 . C h a ra ct er is ti cs o f tu m o r ti ss u es S et a N S iz e (m m ) N o d e in v o lv em en t T N M st a g e N u m b er o f d ea th s

  16. Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

    DTIC Science & Technology

    2008-02-01

    Cancer Society, Atlanta, GA, 2004. 3. Burstein, HJ, Polyak , K, Wong, JS, Lester, SC and Kaelin, CM. Ductal Carcinoma in Situ of the Breast. N Engl J...o f tu m o r ti ss u es S et a N S iz e (m m ) N o d e in v o lv em en t T N M st a g e N u m b er o f d ea th s a t 5 -y ea rs o f fo ll o w u p M

  17. Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

    DTIC Science & Technology

    2007-02-01

    Polyak , K, Wong, JS, Lester, SC and Kaelin, CM. Ductal Carcinoma in Situ of the Breast. N Engl J Med 350:1430-41, 2004. 4. Page DL, Dupont WD...S et a N S iz e (m m ) N o d e in v o lv em en t T N M st a g e N u m b er o f d ea th s a t 5 -y ea rs o f fo ll o w u p M ed ia n M ea n R a n g e

  18. Asymptomatic Incidental Ductal Carcinoma in situ in a Male Breast Presenting with Contralateral Gynecomastia

    PubMed Central

    Isley, Laura M.; Leddy, Rebecca J.; Rumboldt, Tihana; Bernard, Jacqueline M.

    2012-01-01

    Ductal carcinoma in situ (DCIS) in males is rare and usually presents with symptoms on the affected side, such as, palpable mass or bloody nipple discharge. Even as DCIS has been reported in conjunction with gynecomastia in the same breast, we report an unusual case of a 62-year-old Caucasian male, with no family history of breast cancer, who presented with symptomatic side gynecomastia, and was incidentally found to have DCIS in a completely asymptomatic left breast. To the best of our knowledge, this case is the first report in literature of asymptomatic, incidentally discovered DCIS in a male patient. PMID:22530182

  19. Ductal Carcinoma In Situ: Recent Advances and Future Prospects

    PubMed Central

    Lambert, Kelly; Patani, Neill; Mokbel, Kefah

    2012-01-01

    Introduction. This article reviews current management strategies for DCIS in the context of recent randomised trials, including the role of sentinel lymph node biopsy (SLNB), adjuvant radiotherapy (RT) and endocrine treatment. Methods. Literature review facilitated by Medline, PubMed, Embase and Cochrane databases. Results. DCIS should be managed in the context of a multidisciplinary team. Local control depends upon clear surgical margins (at least 2 mm is generally acceptable). SLNB is not routine, but can be considered in patients undergoing mastectomy (Mx) with risk factors for occult invasion. RT following BCS significantly reduces local recurrence (LR), particularly in those at high-risk. There remains a lack of level-1 evidence supporting omission of adjuvant RT in selected low-risk cases. Large, multi-centric or recurrent lesions should be treated by Mx and immediate reconstruction should be discussed. Adjuvant hormonal treatment may reduce the risk of LR in selected cases with hormone sensitive disease. Conclusion. Further research is required to determine the role of new RT regimes and endocrine therapies. Biological profiling and molecular analysis represent an opportunity to improve our understanding of tumour biology in DCIS to rationalise treatment. Reliable identification of low-risk lesions could allow treatment to be less radical. PMID:22675624

  20. Mucinous metaplasia of breast carcinoma with macrocystic transformation resembling ovarian mucinous cystadenocarcinoma in a case of synchronous bilateral infiltrating ductal carcinoma.

    PubMed

    Lee, Sheng-Huang; Chaung, Chen-Rong

    2008-09-01

    Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.

  1. Is Radiation Indicated in Patients With Ductal Carcinoma In Situ and Close or Positive Mastectomy Margins?

    SciTech Connect

    Chan, Linda W.; Rabban, Joseph; Hwang, E. Shelley; Bevan, Alison; Alvarado, Michael; Ewing, Cheryl; Esserman, Laura; Fowble, Barbara

    2011-05-01

    Purpose: Resection margin status is one of the most significant factors for local recurrence in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery with or without radiation. However, its impact on chest wall recurrence in patients treated with mastectomy is unknown. The purpose of this study was to determine chest wall recurrence rates in women with DCIS and close (<5 mm) or positive mastectomy margins in order to evaluate the potential role of radiation therapy. Methods and Materials: Between 1985 and 2005, 193 women underwent mastectomy for DCIS. Fifty-five patients had a close final margin, and 4 patients had a positive final margin. Axillary surgery was performed in 17 patients. Median follow-up was 8 years. Formal pathology review was conducted to measure and verify margin status. Nuclear grade, architectural pattern, and presence or absence of necrosis was recorded. Results: Median pathologic size of the DCIS in the mastectomy specimen was 4.5 cm. Twenty-two patients had DCIS of >5 cm or diffuse disease. Median width of the close final margin was 2 mm. Nineteen patients had margins of <1 mm. One of these 59 patients experienced a chest wall recurrence with regional adenopathy, followed by distant metastases 2 years following skin-sparing mastectomy. The DCIS was high-grade, 4 cm, with a 5-mm deep margin. A second patient developed an invasive cancer in the chest wall 20 years after her mastectomy for DCIS. This cancer was considered a new primary site arising in residual breast tissue. Conclusions: The risk of chest wall recurrence in this series of patients is 1.7% for all patients and 3.3% for high-grade DCIS. One out of 20 (5%) patients undergoing skin sparing or total skin-sparing mastectomy experienced a chest wall recurrence. This risk of a chest wall recurrence appears sufficiently low not to warrant a recommendation for postmastectomy radiation therapy for patients with margins of <5 mm. There were too few patients

  2. Improved Outcomes of Breast-Conserving Therapy for Patients With Ductal Carcinoma in Situ

    SciTech Connect

    Halasz, Lia M.; Sreedhara, Meera; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Harris, Jay R.

    2012-03-15

    Purpose: Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2{sup +} DCIS. Methods and Materials: We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (>2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003. Results: With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR{sup +}HER-2{sup -}, 27 were ER/PR{sup +}HER-2{sup +}, 6 were ER{sup -}/PR{sup -}HER-2{sup +}, and 6 were ER{sup -}/PR{sup -}HER-2{sup -}. On univariable analysis, HER-2{sup +}was significantly associated with Grade III, ER{sup -}/PR{sup -}, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2{sup +}. Conclusions: In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated

  3. Novel clinical trial designs for treatment of ductal carcinoma in situ of the breast with trastuzumab (herceptin).

    PubMed

    Gonzalez, Ricardo J; Buzdar, Aman U; Fraser Symmans, W; Yen, Tina W; Broglio, Kristine R; Lucci, Anthony; Esteva, Francisco J; Yin, Guosheng; Kuerer, Henry M

    2007-01-01

    Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be effective against invasive breast cancer, trastuzumab may be effective for reducing the tumor burden and abrogating or reversing the hypothesized transition from in situ to invasive disease in patients with DCIS. To test this hypothesis, a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution. Because trastuzumab has been shown to act as a radiosensitizing agent for Her2/neu-overexpressing cancer and because there are currently no systemic treatments for estrogen-receptor-negative DCIS, it makes sense to investigate whether use of trastuzumab concurrently with postoperative radiation therapy improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac toxicity associated with the doses of trastuzumab planned for these trials (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is believed to be minimal, but the safety profile of these approaches will need to be closely monitored.

  4. Impact of Boost Radiation in the Treatment of Ductal Carcinoma In Situ: A Population-Based Analysis

    SciTech Connect

    Rakovitch, Eileen; Narod, Steven A.; Nofech-Moses, Sharon; Hanna, Wedad; Thiruchelvam, Deva; Saskin, Refik; Taylor, Carole; Tuck, Alan; Youngson, Bruce; Miller, Naomi; Done, Susan J.; Sengupta, Sandip; Elavathil, Leela; Jani, Prashant A.; Bonin, Michel; Metcalfe, Stephanie; Paszat, Lawrence

    2013-07-01

    Purpose: To report the outcomes of a population of women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and radiation and to evaluate the independent effect of boost radiation on the development of local recurrence. Methods and Materials: All women diagnosed with DCIS and treated with breast-conserving surgery and radiation therapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of boost radiation on the development of local recurrence was determined using survival analyses. Results: We identified 1895 cases of DCIS that were treated by breast-conserving surgery and radiation therapy; 561 patients received boost radiation. The cumulative 10-year rate of local recurrence was 13% for women who received boost radiation and 12% for those who did not (P=.3). The 10-year local recurrence-free survival (LRFS) rate among women who did and who did not receive boost radiation was 88% and 87%, respectively (P=.27), 94% and 93% for invasive LRFS (P=.58), and was 95% and 93% for DCIS LRFS (P=.31). On multivariable analyses, boost radiation was not associated with a lower risk of local recurrence (hazard ratio = 0.82, 95% confidence interval 0.59-1.15) (P=.25). Conclusions: Among a population of women treated with breast-conserving surgery and radiation for DCIS, additional (boost) radiation was not associated with a lower risk of local or invasive recurrence.

  5. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research.

    PubMed

    Hendry, Shona; Salgado, Roberto; Gevaert, Thomas; Russell, Prudence A; John, Tom; Thapa, Bibhusal; Christie, Michael; van de Vijver, Koen; Estrada, M V; Gonzalez-Ericsson, Paula I; Sanders, Melinda; Solomon, Benjamin; Solinas, Cinzia; Van den Eynden, Gert G G M; Allory, Yves; Preusser, Matthias; Hainfellner, Johannes; Pruneri, Giancarlo; Vingiani, Andrea; Demaria, Sandra; Symmans, Fraser; Nuciforo, Paolo; Comerma, Laura; Thompson, E A; Lakhani, Sunil; Kim, Seong-Rim; Schnitt, Stuart; Colpaert, Cecile; Sotiriou, Christos; Scherer, Stefan J; Ignatiadis, Michail; Badve, Sunil; Pierce, Robert H; Viale, Giuseppe; Sirtaine, Nicolas; Penault-Llorca, Frederique; Sugie, Tomohagu; Fineberg, Susan; Paik, Soonmyung; Srinivasan, Ashok; Richardson, Andrea; Wang, Yihong; Chmielik, Ewa; Brock, Jane; Johnson, Douglas B; Balko, Justin; Wienert, Stephan; Bossuyt, Veerle; Michiels, Stefan; Ternes, Nils; Burchardi, Nicole; Luen, Stephen J; Savas, Peter; Klauschen, Frederick; Watson, Peter H; Nelson, Brad H; Criscitiello, Carmen; O'Toole, Sandra; Larsimont, Denis; de Wind, Roland; Curigliano, Giuseppe; André, Fabrice; Lacroix-Triki, Magali; van de Vijver, Mark; Rojo, Federico; Floris, Giuseppe; Bedri, Shahinaz; Sparano, Joseph; Rimm, David; Nielsen, Torsten; Kos, Zuzana; Hewitt, Stephen; Singh, Baljit; Farshid, Gelareh; Loibl, Sibylle; Allison, Kimberly H; Tung, Nadine; Adams, Sylvia; Willard-Gallo, Karen; Horlings, Hugo M; Gandhi, Leena; Moreira, Andre; Hirsch, Fred; Dieci, Maria V; Urbanowicz, Maria; Brcic, Iva; Korski, Konstanty; Gaire, Fabien; Koeppen, Hartmut; Lo, Amy; Giltnane, Jennifer; Rebelatto, Marlon C; Steele, Keith E; Zha, Jiping; Emancipator, Kenneth; Juco, Jonathan W; Denkert, Carsten; Reis-Filho, Jorge; Loi, Sherene; Fox, Stephen B

    2017-09-01

    Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.

  6. Preoperative diagnosis of ductal carcinoma in situ arising within a mammary fibroadenoma: a case report.

    PubMed

    Ooe, Asako; Takahara, Sachiko; Sumiyoshi, Kazuhiro; Yamamoto, Hitoshi; Shiba, Eiichi; Kawai, Jun

    2011-07-01

    Fibroadenoma is the most common form of benign breast tumor and the most common breast tumor in women under 30 years of age. However, carcinoma arising within a fibroadenoma is unusual, with over 100 cases reported in the literature. Histological diagnosis is typically unexpected. A 46-year-old female with no family history of breast malignancies was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. At a clinic that she visited previously, her condition was diagnosed by core needle biopsy with four specimens showing fibroadenoma with borderline atypical ductal hyperplasia at pathology. Excisional biopsy was recommended for pathological diagnosis. The patient requested a definitive diagnosis and alternative treatment to tumorectomy. More biopsy specimens were needed for pathological diagnosis; therefore, ultrasonography-guided vacuum-assisted core needle biopsies were obtained, confirming ductal carcinoma in situ with questionable microinvasion of intracanalicular- and pericanalicular-type fibroadenoma. Right breast-conserving surgery and sentinel lymph node biopsy were immediately performed for radical therapy. We present this case to increase awareness of this entity and stress the need for histological evaluation of some breast masses.

  7. Patient age and breast resection weight affect immediate postmastectomy breast reconstruction in ductal carcinoma in situ.

    PubMed

    Burnier, Pierre; Hudry, Delphine; See, Leslie-Ann; Duvernay, Alain; Roche, Matthieu; Loustalot, Catherine; Zwetyenga, Narcisse; Coutant, Charles

    2016-01-01

    Mastectomy is necessary for 40% of the ductal carcinoma in situ. If immediate breast reconstruction (IBR) is systematically proposed, 81% of the patients would choose immediate versus delayed breast reconstruction, but the actual IBR rate is only approximately 50% of them. Therefore, the aim of this study was to identify objective characteristics that distinguish the patients who actually underwent IBR from those who did not. Several criteria of 248 patients who have undergone mastectomy for ductal carcinoma were analyzed. Factors studied were age, body mass index, diabetes, tobacco use, and weight of the specimen of resection. The rate of IBR was 43%. An increase in age and weight of the resection specimen, irrespective of the body mass index, was associated with a lower rate of IBR. Thus, an increase of 100 g in the weight of the breast induces a significant reduction of the IBR (33%). In our series, older patients or patients with larger breasts (irrespective of the body mass index) were less likely to undergo IBR. In order to be in line with the patient's desire, the surgeons of our unit should broaden their indications of IBR. The lack of reconstruction of large breasts should certainly be compensated in part with the recent development of free tissue transfers in our unit. 3. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Relationship between reticuloendothelial systems' FDG uptake level and clinicopathological features in patient with invasive ductal breast cancer.

    PubMed

    Şahin, Ertan; Elboğa, Umut

    2017-06-09

    The reticuloendothelial system (RES) is a part of the immune system and plays a major role in the protection of against diseases. We thought that FDG-PET/CT may show the degree of systemic immune response induced with malignancy in the organs with the high RES activity. Our objective is to investigate FDG uptake levels of high RES activity organs (liver, spleen, bone marrow) in invasive ductal breast cancer and to evaluate the association with the clinicopathological features. In the present study, 193 patients with invasive ductal breast cancer who performed FDG-PET/CT were categorized according to the clinicopathological features including age, tumor size, axillary nodal status, histological grade, the presence of lymphavascular invasion, receptor status, Ki-67 proliferation index and biological subgroup. Also, a control group of 100 subjects were identified for comparison with breast cancer patients. We analyzed the relation of FDG uptake levels in high RES activity organs and clinicopathological features in patients. There was a statistically significant difference of SUVmax of the liver, spleen, and bone marrow between cancer and control groups (P < 0.0001). We found that high SUVmax in liver, spleen and bone marrow were significantly correlated with worse prognostic clinicopathological features in patient with invasive ductal breast cancer. FDG uptake level in high RES activity organs is associated with the presence of tumor, and also directly relating clinicopathological features for patients with invasive ductal breast cancer.

  9. Pathological controversies in breast cancer: classification of ductal carcinoma in situ, sentinel lymph nodes and low volume metastatic disease and reporting of neoadjuvant chemotherapy specimens.

    PubMed

    Provenzano, E; Brown, J P; Pinder, S E

    2013-02-01

    The pathological classification of breast cancer is constantly being updated to reflect the advances in our clinical and biological understanding of the disease. This overview examines new insights into the classification and molecular biology of ductal carcinoma in situ, the pathological handling of sentinel lymph node biopsies and the identification of low volume disease (micrometastases and isolated tumour cells) and the handling and reporting of specimens after neoadjuvant therapy. The molecular subtypes of invasive breast cancer are also represented in ductal carcinoma in situ. It is hoped that alongside traditional histological features, such as cytological grade and the presence of necrosis, this will lead to better classification systems with improved prediction of clinical behaviour, in particular the risk of progression to invasive cancer, and enable more targeted management. Sentinel lymph node biopsy is now the standard of care for early stage breast cancer in clinically node-negative patients. However, the handling and reporting of these specimens remains controversial, largely related to the uncertainties regarding the clinical significance of micrometastases and isolated tumour cells. The increasing use of neoadjuvant therapies has introduced challenges for the pathologist in the handling and interpretation of these specimens. Grading the tumour response, particularly the identification of a complete pathological response, is prognostically important. However, there is still marked variability in reporting these specimens in routine practice, and consensus guidelines for the histopathology reporting of breast cancers after neoadjuvant chemotherapy based on robust, validated evidence are presently lacking.

  10. Quantitatively characterizing the microstructural features of breast ductal carcinoma tissues in different progression stages by Mueller matrix microscope.

    PubMed

    Dong, Yang; Qi, Ji; He, Honghui; He, Chao; Liu, Shaoxiong; Wu, Jian; Elson, Daniel S; Ma, Hui

    2017-08-01

    Polarization imaging has been recognized as a potentially powerful technique for probing the microstructural information and optical properties of complex biological specimens. Recently, we have reported a Mueller matrix microscope by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission-light microscope, and applied it to differentiate human liver and cervical cancerous tissues with fibrosis. In this paper, we apply the Mueller matrix microscope for quantitative detection of human breast ductal carcinoma samples at different stages. The Mueller matrix polar decomposition and transformation parameters of the breast ductal tissues in different regions and at different stages are calculated and analyzed. For more quantitative comparisons, several widely-used image texture feature parameters are also calculated to characterize the difference in the polarimetric images. The experimental results indicate that the Mueller matrix microscope and the polarization parameters can facilitate the quantitative detection of breast ductal carcinoma tissues at different stages.

  11. Quantifying the extent of invasive carcinoma and margin status in partial mastectomy cases having a gross lesion: is a defined tissue processing protocol needed?

    PubMed

    Sneed, George M; Duncan, Lisa D

    2011-11-01

    Accurate estimation of disease extent and margin status is critical when evaluating partial mastectomy cases because both are predictors of recurrence. No published standards exist for processing specimens involved by invasive carcinoma, presumably because such cases have a gross lesion. We retrospectively studied 100 partial mastectomy cases and concluded that a standardized tissue mapping protocol is needed to ensure adequate pathologic examination even when a gross lesion is present. When mapped and unmapped findings were compared, 17 cases (10 with ductal and 7 with lobular carcinoma) had an increase in carcinoma size, 12 cases (9 with ductal and 3 with lobular carcinoma) had an increase in pathologic T stage, and positive margins were found in 8 cases (7 with ductal and 1 with lobular carcinoma). We describe our tissue-mapping protocol, and advocate its use as a standardized protocol for processing all partial mastectomy specimens.

  12. Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ.

    PubMed

    Wang, Shi-Yi; Long, Jessica B; Killelea, Brigid K; Evans, Suzanne B; Roberts, Kenneth B; Silber, Andrea; Gross, Cary P

    2016-07-01

    Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of invasive disease among women who develop a CBC. Utilizing the Surveillance, Epidemiology, and End Results-Medicare dataset, we assessed overall, synchronous (<6 months after primary cancer diagnosis), and subsequent (≥6 months after diagnosis, i.e., metachronous) CBC occurrence in women aged 67-94 years diagnosed with DCIS during 2004-2009, with follow-up through 2011. We applied a matched propensity score approach to compare the stage-specific incidence rate of CBC according to MRI use. Our sample consisted of 9166 beneficiaries, 1258 (13.7 %) of whom received preoperative MRI. After propensity score matching, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (108.6 vs. 29.7 per 1000 person-years; hazard ratio [HR] = 3.65; p < .001) with no significant differences in subsequent CBC rate (6.7 vs. 6.8 per 1000 person-years; HR = 0.90; p = .71). The 6-year cumulative incidence of any CBC (in situ plus invasive) remained significantly higher among women undergoing MRI, compared with those not undergoing MRI (9 vs. 4 %, p < .001). Women undergoing MRI also had a higher incidence of invasive CBC (4 vs. 3 %, p = .04). MRI use resulted in an increased detection of synchronous CBC but did not prevent subsequent CBC occurrence, suggesting that many of the undetected CBC lesions may not become clinically evident.

  13. A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma

    PubMed Central

    Kwag, Hye Rin; Serbo, Janna V.; Korangath, Preethi; Sukumar, Saraswati

    2016-01-01

    A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma. PMID:26831041

  14. A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma.

    PubMed

    Kwag, Hye Rin; Serbo, Janna V; Korangath, Preethi; Sukumar, Saraswati; Romer, Lewis H; Gracias, David H

    2016-04-01

    A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma.

  15. ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth.

    PubMed

    Rath, Nicola; Morton, Jennifer P; Julian, Linda; Helbig, Lena; Kadir, Shereen; McGhee, Ewan J; Anderson, Kurt I; Kalna, Gabriela; Mullin, Margaret; Pinho, Andreia V; Rooman, Ilse; Samuel, Michael S; Olson, Michael F

    2017-02-01

    Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death; identifying PDAC enablers may reveal potential therapeutic targets. Expression of the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human and mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression in human patients, or conditional ROCK2 activation in a Kras(G12D)/p53(R172H) mouse PDAC model, was associated with reduced survival. Conditional ROCK1 or ROCK2 activation promoted invasive growth of mouse PDAC cells into three-dimensional collagen matrices by increasing matrix remodeling activities. RNA sequencing revealed a coordinated program of ROCK-induced genes that facilitate extracellular matrix remodeling, with greatest fold-changes for matrix metalloproteinases (MMPs) Mmp10 and Mmp13 MMP inhibition not only decreased collagen degradation and invasion, but also reduced proliferation in three-dimensional contexts. Treatment of Kras(G12D)/p53(R172H) PDAC mice with a ROCK inhibitor prolonged survival, which was associated with increased tumor-associated collagen. These findings reveal an ancillary role for increased ROCK signaling in pancreatic cancer progression to promote extracellular matrix remodeling that facilitates proliferation and invasive tumor growth.

  16. Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?

    PubMed

    Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kaku, Tsunehisa; Kato, Kiyoko; Oda, Yoshinao

    2016-01-01

    "Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.

  17. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  18. A review of the management of ductal carcinoma in situ following breast conserving surgery.

    PubMed

    Boxer, M M; Delaney, G P; Chua, B H

    2013-12-01

    Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 10-20% of all new breast tumours. Evidence shows a statistically significant local control benefit for adjuvant radiotherapy (RT) following breast conserving surgery (BCS) for all patients. The baseline recurrence risk of individual patients varies according to clinical-pathological criteria and in selected patients, omission of RT may be considered, following a discussion with the patient. The role of adjuvant endocrine therapy remains uncertain. Ongoing studies are attempting to define subgroups of patients who are at sufficiently low risk of recurrence that RT may be safely omitted; investigating RT techniques and dose fractionation schedules; and defining the role of endocrine therapy. Future directions in the management of patients with DCIS will include investigation of prognostic and predictive biomarkers to inform individualised therapy tailored to the risk of recurrence.

  19. Can MRI biomarkers at 3 T identify low-risk ductal carcinoma in situ?

    PubMed

    Rahbar, Habib; Parsian, Sana; Lam, Diana L; Dontchos, Brian N; Andeen, Nicole K; Rendi, Mara H; Lehman, Constance D; Partridge, Savannah C

    2016-01-01

    The objective was to explore whether 3-T magnetic resonance imaging (MRI) can identify low-risk ductal carcinoma in situ (DCIS). Dynamic contrast-enhanced and diffusion-weighted (DWI) MRI features of 36 DCIS lesions [8 low risk, Van Nuys Pathologic Classification (VNPC) 1; 28 high risk, VNPC 2/3] were reviewed. An MRI model that best identified low-risk DCIS was determined using multivariate logistic regression. Low-risk DCIS exhibited different DWI properties [i.e., higher contrast-to-noise ratio (P=.02) and lower normalized apparent diffusion coefficients (P=.04)] than high-risk DCIS. A model combining these DWI features provided best performance (area under receiver operating characteristic curve =0.86). DWI may help identify DCIS lesions requiring less therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. A rare case of male breast ductal carcinoma in-situ associated with prolactinoma.

    PubMed

    Mallawaarachchi, Chandike Maithri; Ivanova, Snezana; Shorthouse, Alice; Shousha, Sami; Sinnett, Dudley

    2011-08-31

    A case of ductal carcinoma in-situ (DCIS) associated with prolactinoma in a male patient is described. A 56-year-old gentleman presented with lethargy and loss of libido. His prolactin at presentation was 3680 mU/l and an MRI scan of the head revealed a pituitary tumour suggestive of prolactinoma. Following 18 months of treatment with cabergoline, the prolactin level reduced to 914 mU/l. However, 3 years later he presented with blood stained nipple discharge, the cytology of which was negative for cancer. Ultrasound scan of his right breast revealed a single dilated mammary duct. Microdochectomy was performed. The histology revealed incompletely excised DCIS. There is increasing evidence of prolactinoma associated with breast cancer with or without DCIS in females. A review of the literature reveals only one previous case report of this association in males. This is the first case of pure DCIS preceded by prolactinoma in a male patient.

  1. Ductal Carcinoma In Situ: What Can We Learn from Clinical Trials?

    PubMed Central

    Fortunato, Lucio; Poccia, Igor; de Paula, Ugo; Santini, Elena

    2012-01-01

    Ductal Carcinoma in situ has been diagnosed more frequently in the last few years and now accounts for approximately one-fourth of all treated breast cancers. Traditionally, this disease has been treated with total mastectomy, but conservative surgery has become increasingly used in the absence of unfavourable clinical conditions, if a negative excision margin can be achieved. It is controversial whether subgroups of patients with favourable in situ tumors could be managed by conservative surgery alone, without radiation. As the disease is diagnosed more frequently in younger patients, these issues are very relevant, and much research has focused on this topic in the last two decades. We reviewed randomized trials regarding adjuvant radiation after breast-conservative surgery and compared data with available retrospective studies. PMID:22649720

  2. Protocol for Biomarker Ratio Imaging Microscopy with Specific Application to Ductal Carcinoma In situ of the Breast

    PubMed Central

    Clark, Andrea J.; Petty, Howard R.

    2016-01-01

    This protocol describes the methods and steps involved in performing biomarker ratio imaging microscopy (BRIM) using formalin fixed paraffin-embedded (FFPE) samples of human breast tissue. The technique is based on the acquisition of two fluorescence images of the same microscopic field using two biomarkers and immunohistochemical tools. The biomarkers are selected such that one biomarker correlates with breast cancer aggressiveness while the second biomarker anti-correlates with aggressiveness. When the former image is divided by the latter image, a computed ratio image is formed that reflects the aggressiveness of tumor cells while increasing contrast and eliminating path-length and other artifacts from the image. For example, the aggressiveness of epithelial cells may be assessed by computing ratio images of N-cadherin and E-cadherin images or CD44 and CD24 images, which specifically reflect the mesenchymal or stem cell nature of the constituent cells, respectively. This methodology is illustrated for tissue samples of ductal carcinoma in situ (DCIS) and invasive breast cancer. This tool should be useful in tissue studies of experimental cancer as well as the management of cancer patients. PMID:27857940

  3. Implications on glycobiological aspects of tumor hypoxia in breast ductal carcinoma in situ.

    PubMed

    Rêgo, Moacyr Jesus Barreto de Melo; Vieira de Mello, Gabriela Souto; da Silva Santos, Carlos André; Chammas, Roger; Beltrão, Eduardo Isidoro Carneiro

    2013-06-01

    Breast carcinoma is one of the most common neoplasia and the first cause of women cancer related deaths worldwide. In the past few years with diagnostic increment, the number of patients diagnosed with ductal carcinoma in situ (DCIS) increased considerably and opened up new ways in research and new dilemmas in diagnostic and clinical practice. This work aimed to evaluate differences in Galectin-1 and Galectin-3 expression and lectins ligands profile on DCIS cells in hypoxic microenvironment. Lectin histochemistry and immunohistochemistry were performed with Concanavalin A, Wheat Germ Agglutinin, Peanut Agglutinin and Ulex europaeus Agglutinin lectins and with anti-Galectin-1 and anti-Galectin-3 antibodies. Lectin ligands were more recognized in hypoxic lesions by Concanavalin A (p = 0.0019), Wheat Germ Agglutinin (p < 0.001) and Ulex europaeus Agglutinin (p = 0.0014), but not by Peanut Agglutinin (p = 0.5779) when compared to non-hypoxic. Galectin-1 was not observed in all cases analyzed on both groups, differing from Galectin-3 that was overexpressed on cytoplasm of DCIS hypoxic group in relation to control group (p = 0.031). As far as we are concerned, this is the first paper that describes glycobiological alterations in breast cancer hypoxic environment in vivo that could be used to validate in vitro models on this aspect. Moreover, comedogenic/necrotic carcinomas were usually associated with poor-prognostic than others, and our results show that glycosylation may play an important role in this event.

  4. Efficacy of Contrast-enhanced Harmonic Endoscopic Ultrasonography in the Diagnosis of Pancreatic Ductal Carcinoma

    PubMed Central

    Uekitani, Toshiyuki; Kaino, Seiji; Harima, Hirofumi; Suenaga, Shigeyuki; Sen-yo, Manabu; Sakaida, Isao

    2016-01-01

    Background/Aims: Distinguishing pancreatic ductal carcinoma (DC) from other pancreatic masses remains challenging. This study aims at evaluating the efficacy of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) in the diagnosis of DC. Patients and Methods: Forty-nine patients with solid pancreatic mass lesions underwent CEH-EUS. EUS (B-mode) was used to evaluate the inner echoes, distributions, and borders of the masses. The vascular patterns of the masses were evaluated with CEH-EUS at 30–50 s (early phase) and 70–90 s (late phase) after the administration of Sonazoid®. Results: The final diagnoses included DCs (37), mass-forming pancreatitis (6), endocrine neoplasms (3), a solid pseudopapillary neoplasm (1), a metastatic carcinoma (1), and an acinar cell carcinoma (1). The sensitivity, specificity, and accuracy of the diagnoses of DC in hypoechoic masses using EUS (B-mode) were 89.2%, 16.7%, and 71.4%, respectively. The sensitivity, specificity, and accuracy for the diagnosis of DC in hypovascular masses using CEH-EUS were 73.0%, 91.7%, and 77.6% in the early phase and 83.8%, 91.7%, and 85.7% in the late phase, respectively. Conclusions: CEH-EUS for the diagnosis of DC is superior to EUS. CEH-EUS in the late phase was particularly efficacious in the diagnosis of DC. PMID:27184637

  5. Glucose Uptake and Intracellular pH in a Mouse Model of Ductal Carcinoma In situ (DCIS) Suggests Metabolic Heterogeneity

    PubMed Central

    Lobo, Rebecca C.; Hubbard, Neil E.; Damonte, Patrizia; Mori, Hidetoshi; Pénzváltó, Zsófia; Pham, Cindy; Koehne, Amanda L.; Go, Aiza C.; Anderson, Steve E.; Cala, Peter M.; Borowsky, Alexander D.

    2016-01-01

    Mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast carcinoma remain unclear. Previously we showed that the transition to invasiveness in the mammary intraepithelial neoplastic outgrowth (MINO) model of DCIS does not correlate with its serial acquisition of genetic mutations. We hypothesized instead that progression to invasiveness depends on a change in the microenvironment and that precancer cells might create a more tumor-permissive microenvironment secondary to changes in glucose uptake and metabolism. Immunostaining for glucose transporter 1 (GLUT1) and the hypoxia marker carbonic anhydrase 9 (CAIX) in tumor, normal mammary gland and MINO (precancer) tissue showed differences in expression. The uptake of the fluorescent glucose analog dye, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG), reflected differences in the cellular distributions of glucose uptake in normal mammary epithelial cells (nMEC), MINO, and Met1 cancer cells, with a broad distribution in the MINO population. The intracellular pH (pHi) measured using the fluorescent ratio dye 2′,7′-bis(2-carboxyethyl)-5(6)-155 carboxyfluorescein (BCECF) revealed expected differences between normal and cancer cells (low and high, respectively), and a mixed distribution in the MINO cells, with a subset of cells in the MINO having an increased rate of acidification when proton efflux was inhibited. Invasive tumor cells had a more alkaline baseline pHi with high rates of proton production coupled with higher rates of proton export, compared with nMEC. MINO cells displayed considerable variation in baseline pHi that separated into two distinct populations: MINO high and MINO low. MINO high had a noticeably higher mean acidification rate compared with nMEC, but relatively high baseline pHi similar to tumor cells. MINO low cells also had an increased acidification rate compared with nMEC, but with a more acidic pHi similar to nMEC. These findings

  6. Evaluating Human Breast Ductal Carcinomas with High-Resolution Magic-Angle Spinning Proton Magnetic Resonance Spectroscopy

    NASA Astrophysics Data System (ADS)

    Cheng, Leo Ling; Chang, I.-Wen; Smith, Barbara L.; Gonzalez, R. Gilberto

    1998-11-01

    We report the results of a study of human breast ductal carcinomas, conducted by using high resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1HMRS). This recently developed spectroscopic technique can measure tissue metabolism from intact pathological specimens and identify tissue biochemical changes, which closely correspond to tumorin vivostate. This procedure objectively indicates diagnostic parameters, independent of the skill and experience of the investigator, and has the potential to reduce the sampling errors inherently associated with procedures of conventional histopathology. In this study, we measured 19 cases of female ductal carcinomas. Our results demonstrate that: (1) highly resolved spectra of intact specimens of human breast ductal carcinomas can be obtained; (2) carcinoma-free tissues and carcinomas are distinguishable by alterations in the intensities and the spin-spin relaxation time T2 of cellular metabolites; and (3) tumor metabolic markers, such as phosphocholine, lactate, and lipids, may correlate with the histopathological grade determined from evaluation of the adjacent specimen. Our results suggest that biochemical markers thus measured may function as a valuable adjunct to histopathology to improve the accuracy of and reduce the time frame required for the diagnosis of human breast cancer.

  7. Treatment for ductal carcinoma in situ in an Asian population: outcome and prognostic factors.

    PubMed

    Chuwa, Esther W L; Tan, Vincent H S; Tan, Puay-Hoon; Yong, Wei-Sean; Ho, Guy-Hui; Wong, Chow-Yin

    2008-01-01

    Breast cancer is the most common cancer among Singapore women and ductal carcinoma in situ (DCIS) is believed to be the precursor of most invasive breast cancers. The incidence of DCIS has increased dramatically with mammographic screening, but its treatment remains controversial. Further, results of treatment for DCIS in Asians, and in particular Singapore women, are lacking. We review our institution's results treating a predominantly Chinese population with DCIS of the breast before the introduction of mammographic screening and aim to determine treatment outcomes and identify prognostic factors for disease recurrence. Between January 1994 and December 2000, 170 consecutive patients with DCIS were treated at our institution. One hundred and three (60.5%) were managed with breast conservation (17 with local wide excision alone and 86 with adjuvant irradiation following wide excision) whereas 67 (39.4%) underwent mastectomy. Of those who underwent wide local excision, 56 (54.3%) underwent re-excision for margin clearance. Overall, the axilla was surgically staged in 47 (27.6%) and no nodal involvement was found in all cases. Pathological specimens were reviewed by one of the authors. Median follow up was 86 months (range 4-151 months). Sixty-two patients (36%) were asymptomatic at presentation whereas most (64%) presented with clinical symptoms; out of these more than half (54%) presented with a palpable lump. The median size of tumours was 13 mm (range 1.5-90 mm). Patients who underwent breast conservation surgery had oncologically more favourable lesions - with a significantly higher incidence of smaller and non-palpable lesions and lesions of lower nuclear grade. However, there was also a significantly higher incidence of local recurrence in this group. At the end of follow up, there were 12 patients (7.1%) who developed local recurrence and 8 patients (4.7%) developed contralateral disease. The crude incidence of all breast events (including both local failure

  8. Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS).

    PubMed

    Chen, Youdinghuan; Marotti, Jonathan D; Jenson, Erik G; Onega, Tracy L; Johnson, Kevin C; Christensen, Brock C

    2017-08-01

    The utility and reliability of assessing molecular biomarkers for translational applications on pre-operative core biopsy specimens assume consistency of molecular profiles with larger surgical specimens. Whether DNA methylation in ductal carcinoma in situ (DCIS), measured in core biopsy and surgical specimens are similar, remains unclear. Here, we compared genome-scale DNA methylation measured in matched core biopsy and surgical specimens from DCIS, including specific DNA methylation biomarkers of subsequent invasive cancer. DNA was extracted from guided 2mm cores of formalin fixed paraffin embedded (FFPE) specimens, bisulfite-modified, and measured on the Illumina HumanMethylation450 BeadChip. DNA methylation profiles of core biopsies exhibited high concordance with matched surgical specimens. Within-subject variability in DNA methylation was significantly lower than between-subject variability (all P<2.20E-16). In 641 CpGs whose methylation was related with increased hazard of invasive breast cancer, lower within-subject than between-subject variability was observed in 92.3% of the study participants (P<0.05). Between patient-matched core biopsy and surgical specimens, <0.6% of CpGs measured had changes in median DNA methylation >15%, and a pathway analysis of these CpGs indicated enrichment for genes related with wound healing. Our results indicate that DNA methylation measured in core biopsies are representative of the matched surgical specimens and suggest that DCIS biomarkers measured in core biopsies can inform clinical decision-making. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Role of HGF in epithelial–stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ

    PubMed Central

    2013-01-01

    Introduction Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal–epithelial interactions evolve in benign and pre-invasive lesions. Methods To study epithelial–stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and MCF10AT1). Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis. Results Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulated the HGF receptor MET. In three-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with the basal-like subtype, with approximately 86% of basal-like cancers highly expressing the HGF signature, and because high expression of HGF signature was associated with poor survival. Conclusions Coordinated and complementary changes in HGF/MET expression occur in epithelium and stroma during progression of pre-invasive basal-like lesions. These results suggest that

  10. Variations in the management of the axilla in screen-detected ductal carcinoma in situ: evidence from the UK NHS breast screening programme audit of screen detected DCIS.

    PubMed

    Nicholson, S; Hanby, A; Clements, K; Kearins, O; Lawrence, G; Dodwell, D; Bishop, H; Thompson, A

    2015-01-01

    The diagnosis and surgical management of screen-detected Ductal Carcinoma In Situ (DCIS) remains controversial including a range of axillary approaches and consequent morbidity. This study examined the management of the axilla in all patients with DCIS presenting through the United Kingdom National Health Service Breast Screening Programme (UK NHS BSP). Retrospective analysis of the UK NHS BSP identified 26,696 women initially diagnosed with DCIS over the 8 years 1 April 2003-31 March 2011. The final breast pathology of these women was upgraded to invasive ductal cancer in 5564 (20.8%) women or micro-invasive cancer in 1031 (3.9%) women. At first operation, 5290 (26.3%) of the 20,094 women who had a final post-operative diagnosis of DCIS only underwent axillary surgery (72.4% at the time of mastectomy, 23.8% breast conservation surgery, 3.8% axillary surgery alone). Performance of axillary surgery reflected increasing tumour size, micro-invasion or increasing nuclear grade for the final diagnosis of DCIS. More extensive nodal surgery was performed in those undergoing mastectomy; 10.8% of women had more than 8 nodes removed. Overall, 12.0% of women with invasive cancer, 1.7% with micro-invasion, and 0.2% with DCIS alone, were ultimately node positive. Improved pre-operative sampling of DCIS, axillary assessment by ultrasound with needle biopsy for suspected metastases, risk stratification for sentinel node biopsy (for high grade or extensive DCIS) and avoiding axillary clearance for a pre-operative diagnosis of DCIS alone should reduce unnecessary axillary surgery. Standards using such criteria for axillary surgery in screen-detected DCIS should be integrated into the NHS BSP. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  11. Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast.

    PubMed

    Chan, C M; Baratta, F S; Ozzello, L; Ceriani, R L

    1994-01-01

    Monoclonal antibody (MoAb) BrE-3, an anti-human milk fat globule (HMFG) MoAb, is used here as a novel prognostic indicator for survival and relapse time in patients with infiltrating ductal carcinoma of the breast. A scoring system (4-Score method) was developed to this effect that measured, in a statistically reliable fashion, the level of expression of the epitope for MoAb BrE-3 in the cytoplasm and membranes of breast carcinoma cells in paraffin-embedded sections. In univariate analysis, data obtained by the 4-Score Method as well as data from traditional prognostic indicators (tumor size, axillary node status, and grade of differentiation) were found to be associated with patient survival and relapse. In multivariate analysis, using a Cox proportional hazards regression model, levels of expression of BrE-3 epitope plus tumor size and axillary node status were weighted and combined in an Individual Linear Composite Prognostic Score (ILCPS) that had a high level of association with survival and relapse time in this sample model of patients with infiltrating ductal carcinoma of the breast. This level of association was found to be higher than the level of association for any other combination of traditional or 4-Score method variables. The level of expression of BrE-3 significantly adds to the prognostic capacity of traditional prognostic markers for infiltrating ductal carcinoma of the breast.

  12. Immunostaining of ductal breast carcinomas with the monoclonal-antibody-h.

    PubMed

    Arvanitis, D; Kouklis, P; Demoro, G; Goutas, N; Kittas, C; Szuchet, S

    1995-11-01

    Twenty cases of infiltrating ductal breast carcinomas were stained with the mouse monoclonal antibody H, an IgM, in order to estimate the distribution of the epitope (a carbohydrate moiety) recognized by this antibody in the malignant cells. The results showed that in all cases examined, the epitope was present in the cytoplasm of the neoplastic cells arranged mainly in a diffuse pattern. To identify the polypeptides that carry this epitope, we used extracts from the MCF-7 human breast carcinoma eel line in immunoblotting experiments. In addition to cytokeratin 8 this epitope was also found on five polypeptides originating from Triton X-100-soluble (M(r)x10(-3) of 232, 67, and 37) and from the Triton X-100-insoluble (M(r)x10(-3) of 51, and 50) fractions, respectively. The contribution, if any, of these polypeptides to the staining patterns is not known. These data reveal the existence of a common epitope between cytokeratin 8 and other cellular polypeptides. They also serve as a note of caution in the interpretation of immunohistochemical staining when anti-cytokeratin antibodies are used.

  13. Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast.

    PubMed

    Jacobs, Carmel; Clemons, Mark; Addison, Christina; Robertson, Susan; Arnaout, Angel

    2016-01-01

    Invasive lobular carcinoma (ILC) of the breast is the second most common type of invasive breast carcinoma accounting for 8-14% of all breast cancers. Traditional management of ILC has followed similar paradigms as that for invasive ductal carcinoma (IDC). However, ILC represents a pathologically, clinically and biologically unique variant of breast cancer with particular management challenges. These challenges are seen in both the loco-regional management of ILC; where ILC tumors tend to avoid detection and hence present as more clinically advanced and surgically challenging carcinomas, and the systemic management with a unique response pattern to standard systemic therapies. Because of these challenges, the outcome for patients with ILC has likely lagged behind the continued improvements seen in outcome for patients with IDC. Here, we discuss some of the unique challenges ILC presents and discuss possible management strategies to best overcome the difficulties in the loco-regional and systemic management of patients with ILC.

  14. Diagnostic underestimation of atypical ductal hyperplasia and ductal carcinoma in situ at percutaneous core needle and vacuum-assisted biopsies of the breast in a Brazilian reference institution*

    PubMed Central

    Badan, Gustavo Machado; Roveda Júnior, Decio; Piato, Sebastião; Fleury, Eduardo de Faria Castro; Campos, Mário Sérgio Dantas; Pecci, Carlos Alberto Ferreira; Ferreira, Felipe Augusto Trocoli; D'Ávila, Camila

    2016-01-01

    Objective To determine the rates of diagnostic underestimation at stereotactic percutaneous core needle biopsies (CNB) and vacuum-assisted biopsies (VABB) of nonpalpable breast lesions, with histopathological results of atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) subsequently submitted to surgical excision. As a secondary objective, the frequency of ADH and DCIS was determined for the cases submitted to biopsy. Materials and Methods Retrospective review of 40 cases with diagnosis of ADH or DCIS on the basis of biopsies performed between February 2011 and July 2013, subsequently submitted to surgery, whose histopathological reports were available in the internal information system. Biopsy results were compared with those observed at surgery and the underestimation rate was calculated by means of specific mathematical equations. Results The underestimation rate at CNB was 50% for ADH and 28.57% for DCIS, and at VABB it was 25% for ADH and 14.28% for DCIS. ADH represented 10.25% of all cases undergoing biopsy, whereas DCIS accounted for 23.91%. Conclusion The diagnostic underestimation rate at CNB is two times the rate at VABB. Certainty that the target has been achieved is not the sole determining factor for a reliable diagnosis. Removal of more than 50% of the target lesion should further reduce the risk of underestimation. PMID:26929454

  15. Biologic behavior and long-term outcomes of breast ductal carcinoma in situ with microinvasion

    PubMed Central

    Wang, Wei; Fei, Xiaochun; Zong, Yu; Chen, Xiaosong; Huang, Ou; He, Jianrong; Chen, Weiguo; Li, Yafen; Shen, Kunwei; Zhu, Li

    2016-01-01

    Background Ductal carcinoma in situ with microinvasion (DCIS-Mi) generally has favorable prognosis, but the long-term outcomes of DCIS-Mi and the biologic evolution from ductal carcinoma in situ (DCIS), DCIS-Mi, to DCIS with T1a breast cancer (DCIS-T1a) has not been specified. The aim of our study was to explore the biological and prognostic features of DCIS-Mi, compared with pure DCIS and DCIS-T1a. Results After a median follow-up of 31 months, the 3-year estimated disease free survival(DFS) rate of DCIS-Mi patients was significantly lower than that of pure DCIS patients (89.5% vs 97.1%, P=0.009). Patients with DCIS-Mi or DCIS-T1a tumors had comparable 3-year estimated DFS rates (89.5% vs 94.3%, P=0.13). No significant difference in overall survival (OS) was found among different groups (99.6%, 100% and 99.1% for DCIS, DCIS-Mi and DCIS-T1a, P=0.797). In chemotherapy and trastuzumab-naive DCIS-Mi patients, human epidermal growth factor receptor2 (HER2) positivity (HR=21.8, 95%CI, 1.7-286.8, P=0.019) were independent predictor of worse DFS on multivariate analysis. Methods During September 2002 and December 2014, 602 breast cancer patients who underwent radical surgery were retrospectively reviewed. Three hundred and fifty-nine patients (59.6%) had pure DCIS, 84(14.0%) and 159(26.4%) were diagnosed as DCIS-Mi and DCIS-T1a. Clinico-pathological features were compared between different subgroups. Conclusions DCIS-Mi displayed a comparable survival to that of DCIS-T1a and a more aggressive biological nature than pure DCIS. Patients with HER2-positive DCIS-Mi had a worse survival and adjuvant chemotherapy plus target therapy needs to be further optimized in those patients. PMID:27577080

  16. Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data.

    PubMed

    Laurinavicius, Arvydas; Laurinaviciene, Aida; Ostapenko, Valerijus; Dasevicius, Darius; Jarmalaite, Sonata; Lazutka, Juozas

    2012-03-16

    Molecular studies of breast cancer revealed biological heterogeneity of the disease and opened new perspectives for personalized therapy. While multiple gene expression-based systems have been developed, current clinical practice is largely based upon conventional clinical and pathologic criteria. This gap may be filled by development of combined multi-IHC indices to characterize biological and clinical behaviour of the tumours. Digital image analysis (DA) with multivariate statistics of the data opens new opportunities in this field. Tissue microarrays of 109 patients with breast ductal carcinoma were stained for a set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16). Aperio imaging platform with the Genie, Nuclear and Membrane algorithms were used for the DA. Factor analysis of the DA data was performed in the whole group and hormone receptor (HR) positive subgroup of the patients (n = 85). Major factor potentially reflecting aggressive disease behaviour (i-Grade) was extracted, characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α. The i-Grade factor scores revealed bimodal distribution and were strongly associated with higher Nottingham histological grade (G) and more aggressive intrinsic subtypes. In HR-positive tumours, the aggressiveness of the tumour was best defined by positive Ki67 and negative ER loadings. High Ki67/ER factor scores were strongly associated with the higher G and Luminal B types, but also were detected in a set of G1 and Luminal A cases, potentially indicating high risk patients in these categories. Inverse relation between HER2 and PR expression was found in the HR-positive tumours pointing at differential information conveyed by the ER and PR expression. SATB1 along with HIF-1α reflected the second major factor of variation in our patients; in the HR-positive group they were inversely associated with the HR and BCL2 expression and represented the major factor of variation. Finally, we

  17. Regression analysis of the initial karyometric data on tumor cells in ductal carcinoma and fibroadenoma of the mammary gland.

    PubMed

    Kirillov, Vladimir; Akimova, Lydmila

    2010-04-01

    To reveal the differences in the parameters of the second order regression curve with a cluster of experimental points on scattergrams showing the dependence of the perimeter on the area of tumor cell nuclei between ductal carcinoma and fibroadenoma of the mammary gland. Punctate smears taken from patients with ductal carcinoma and fibroadenoma of the mammary gland with coincident histologic and cytologic conclusion were studied and selected. Karyometry of tumor cells was performed with the help of a semiautomatic computer analyzer of digital images. It has been shown that the cluster of experimental points on scattergrams showing the dependence of the perimeter on the area of tumor cell nuclei can be well described by a second order regression curve, which is a parabola. The differences in parabola parameters (coefficients of the parabola equation) characterizing the population of tumor cells in ductal carcinoma and fibroadenoma of the mammary gland were revealed. Boundary values of these parameters in the groups of comparison were ascertained. Parameters of the regression curve to a cluster of experimental points on scattergrams showing the dependence of the perimeter on the area of tumor cell nuclei can be used as an additional diagnostic criterion for breast cancer.

  18. Biologic features and prognosis of ductal carcinoma in situ are not adversely impacted by initial large body mass.

    PubMed

    Kuerer, Henry M; Lari, Sara A; Arun, Banu K; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A; Albarracin, Constance T; Babiera, Gildy V; Caudle, Abigail S; Wagner, Jamie L; Litton, Jennifer K; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K

    2012-06-01

    Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m(2)), overweight (BMI 25 to <30 kg/m(2)), or of normal weight or underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local-regional recurrence was calculated using the Kaplan-Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66-5.80) or Hispanic (OR, 1.44; CI, 1.02-2.04), be postmenopausal (OR, 1.63; CI, 1.28-2.07), have diabetes (OR, 4.60; CI, 2.60-8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00-192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01-1.80). At a median follow-up time of 4.96 years (range, 1.0-14.34 years), no significant differences in local recurrence rates were detected based on patients' initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS.

  19. The Impact of Preoperative Magnetic Resonance Imaging on Surgical Treatment and Outcomes for Ductal Carcinoma In Situ

    PubMed Central

    Itakura, Kaoru; Lessing, Juan; Sakata, Theadora; Heinzerling, Amy; Vriens, Eline; Wisner, Dorota; Alvarado, Michael; Esserman, Laura; Ewing, Cheryl; Hylton, Nola; Hwang, E. Shelley

    2014-01-01

    Background Although magnetic resonance imaging (MRI) is a useful imaging modality for invasive cancer, its role in preoperative surgical planning for ductal carcinoma in situ (DCIS) has not been established. We sought to determine whether preoperative MRI affects surgical treatment and outcomes in women with pure DCIS. Patients and Methods We reviewed consecutive records of women diagnosed with pure DCIS on core biopsy between 2000 and 2007. Patient characteristics, surgical planning, and outcomes were compared between patients with and without preoperative MRI. Multivariable regression was performed to determine which covariates were independently associated with mastectomy or sentinel lymph node biopsy (SLNB). Results Of 149 women diagnosed with DCIS, 38 underwent preoperative MRI. On univariate analysis, patients undergoing MRI were younger (50 years vs. 59 years; P < .001) and had larger DCIS size on final pathology (1.6 cm vs. 1.0 cm; P = .007) than those without MRI. Mastectomy and SLNB rates were significantly higher in the preoperative MRI group (45% vs. 14%, P < .001; and 47% vs. 23%, P = .004, respectively). However, there were no differences in number of re-excisions, margin status, and margin size between the two groups. On multivariate analysis, preoperative MRI and age were independently associated with mastectomy (OR, 3.16, P = .018; OR, 0.95, P = .031, respectively), while multifocality, size, and family history were not significant predictors. Conclusion We found a strong association between preoperative MRI and mastectomy in women undergoing treatment for DCIS. Additional studies are needed to examine the increased rates of mastectomy as a possible consequence of preoperative MRI for DCIS. PMID:21421520

  20. [Ductal carcinoma in situ of the breast (DCIS) under 40: a specific management?].

    PubMed

    Tunon de Lara, C

    2008-05-01

    Ductal carcinoma in situ of the breast (DCIS) is rare in younger women, accounting for about 4% of all cases of DCIS in France, and tends to be diagnosed by clinical findings or casually, after plastic surgery. After breast conserving treatment, young age ( less than 40) is a predictive factor of relapses in patients with DCIS. Age may serve as one more parameter that should be considered in the complex decision-making process necessary to create a treatment plan for a woman with DCIS. Breast conservative treatment (BCT) could be used if: margins are free and more than 10 mm; if DCIS size is less than 11 mm and DCIS is free of necrosis and comedocarcinoma. Mastectomy ought to be proposed in case of: multifocal DCIS, or DCIS size more than 30 mm; invaded margins after re-excision; radiotherapy contraindicated; small breasts and patient choice. Immediate breast reconstruction should be proposed for patients with all the poor predictive factors. In other cases, treatment procedure will be explained to the patient and the treatment will be chosen by the patient in consultation with the medical team (radiologist, surgeon, pathologist and oncologist). Radiotherapy with boost or hormonotherapy with tamoxifen should not be used routinely but may be proposed individually.

  1. Ductal carcinoma in situ (DCIS) of the breast: the need for psychosocial research.

    PubMed

    Carrera, C; Payne, S

    1999-01-01

    Since the introduction of the National Health Service Breast Screening Programme (NHSBSP), the number of ductal carcinoma in situ (DCIS) cases has increased considerably. Despite its increased incidence, some NHS leaflets and reports do not mention it, and the general public seems largely unaware of its existence. There are numerous biological studies dealing with this condition, but its psychosocial aspects seem to have been neglected. We have only been able to locate two British studies (Farmer, A. 1996. Unpublished PhD thesis, University of Southampton; Webb, C. and Koch, T. 1997. J. Adv. Nurs., 25, 154-525) that address some of the psychosocial issues associated with DCIS. This paper starts by defining DCIS and explaining its usual presentation, natural history and epidemiology. The treatment options for DCIS are described, together with the great deal of confusion and lack of agreement that accompanies them. The psychological issues that women with screen-detected DCIS have to deal with are different from those affecting women diagnosed with symptomatic breast cancer, and a summary of these issues is given. Finally, some suggestions for future psychosocial research are provided. Because the UK as a whole was not covered by the NHSBSP until 1990 (Baum, M. 1995. Lancet, 346, 436; Gage and Fouquet, 1997), the main focus will be on papers published from that year onwards, although some key papers published before then will also be included. The papers reviewed here were found in MEDLINE, EMBASE and BIDS (ISI).

  2. The Impact of Surgery on Ductal Carcinoma In Situ Outcomes: The Use of Mastectomy

    PubMed Central

    2010-01-01

    Mastectomy has been the historical mainstay of treatment for ductal carcinoma in situ (DCIS), but over time, there have been significant changes in its use for preinvasive breast cancer. Although there was an early reduction in mastectomy rates for DCIS with the introduction of breast-conserving surgery, in some groups, the rates of both mastectomy and contralateral mastectomy for DCIS have increased in recent years. Due to advances in breast cancer screening as well as improvements in breast reconstruction, mastectomy will continue to be an important and acceptable treatment option. Recurrence is rare following mastectomy for DCIS. Nevertheless, there remains a need to follow patients for in-breast, nodal, or contralateral breast events, which can occur long after the index DCIS has been treated. Since up to 70% of women with newly diagnosed DCIS have disease that can be managed with breast-conserving surgery, patient counseling is imperative to ensure the best use of this option for DCIS, given that mastectomy does not significantly impact survival in this setting. PMID:20956829

  3. FT-raman spectra of the border of infiltrating ductal carcinoma lesions.

    PubMed

    de Miranda Marzullo, Ana Carolina; Neto, Osmar Pinto; Bitar, Renata Andrade; da Silva Martinho, Herculano; Martin, Airton Abrahão

    2007-10-01

    The characterization of the FT-Raman spectra of the borders of lesions is of great importance in guiding the surgeon during surgical intervention. The main goals of this study were to investigate spectra of the borders of lesions of samples of infiltrating ductal carcinoma (IDC) and to determine the characteristics of these spectra. A total of 93 spectra were collected from five samples of healthy tissues and from 13 samples of IDC breast tissues using FT-Raman spectroscopy. Cluster analysis was used to separate the spectra into different groups. The results obtained from the statistical analysis were confirmed by a histopathological analysis. The results showed that 17 out of the 67 spectra collected from the IDC samples demonstrated wide variety. The only significant difference between the peaks of the spectra of normal tissues and those of lesion borders is a peak at 538 cm(1) . This peak is related to disulfide bridges in cysteine, and it seems to be the main factor for the FT-Raman determination of the boundaries between healthy and pathological tissue. These results serve as a foundation for future studies and application of Raman spectroscopy for optical diagnosis to guide biopsy and surgical intervention.

  4. Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ.

    PubMed

    Estévez, Laura G; Suarez-Gauthier, Ana; García, Elena; Miró, Cristina; Calvo, Isabel; Fernández-Abad, María; Herrero, Mercedes; Marcos, Manuel; Márquez, Cristina; Lopez Ríos, Fernando; Perea, Sofía; Hidalgo, Manuel

    2014-09-04

    Human epidermal growth factor receptor 2 (HER2) amplification is frequent in ductal carcinoma in situ (DCIS) of the breast and is associated with poorly differentiated tumors and adverse prognosis features. This study aimed to determine the molecular effects of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS. Patients with HER2 positive DCIS received 1,500 mg daily of lapatinib for four consecutive weeks prior to surgical resection. Magnetic resonance imaging (MRI) was used to determine changes in tumor volume. The molecular effects of lapatinib on HER2 signaling (PI3K/AKT and RAS/MAPK pathways), cell proliferation (Ki67 and p27) and apoptosis (TUNEL) were determined in pre and post-lapatinib treatment samples. A total of 20 patients were included. Lapatinib was well tolerated with only minor and transient side effects. The agent effectively modulated HER2 signaling decreasing significantly pHER2 and pERK1 expression, together with a decrease in tumor size evaluated by MRI. There was no evidence of changes in Ki67. Four weeks of neoadjuvant lapatinib in patients with HER2-positive DCIS resulted in inhibition of HER2 and RAS/MAPK signaling pathway. 2008-004492-21 (Registered June 25th 2008).

  5. Classification of ductal carcinoma in-situ by image analysis of calcifications from mammograms

    NASA Astrophysics Data System (ADS)

    Parker, Jon; Dance, David R.; Davies, David H.; Yeoman, L. J.; Michell, M. J.; Humphreys, S.

    1993-07-01

    Image analysis methods have been developed to characterize calcifications associated with Ductal Carcinoma in-Situ (DCIS), and to differentiate between those having comedo or non- comedo histology. Cases were selected from the U.K. breast screening program, and in each case the histology and a magnified mammographic view were obtained. The films were digitized at 25 micron sampling size and 8 bit grey level resolution. Calcifications were manually segmented from the normal breast background, and a radiologist, experienced in breast screening, checked the labelling of a calcifications. An algorithm was developed to classify firstly the individual objects within a film, and secondly the film itself. The algorithm automatically selected the combination of features giving the least estimated Bayes error for a set of object-oriented features evaluated for each calcification. The k-nearest neighbors statistical approach was then used to classify individual objects giving a ratio of comedo to non-comedo objects for a set of training films. Films were classified by applying a threshold to this ratio. In the classification of typical comedo from typical non-comedo the success rate of the algorithm was 100% for a training set of 4 cases and test set of 16 cases.

  6. Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and comedo necrosis.

    PubMed

    Chishiki, Mayuko; Takagi, Kiyoshi; Sato, Ai; Miki, Yasuhiro; Yamamoto, Yuta; Ebata, Akiko; Shibahara, Yukiko; Watanabe, Mika; Ishida, Takanori; Sasano, Hironobu; Suzuki, Takashi

    2017-07-01

    It is well known that comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ (DCIS) of human breast, but its molecular mechanisms remain largely unclear. Therefore, in this study, we first examined the gene expression profile of comedo DCIS based on microarray data and identified CYC1 as a gene associated with comedo necrosis. Cytochrome c1 (CYC1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production. However, the significance of CYC1 has not yet been examined in DCIS. We therefore immunolocalized CYC1 in 47 DCIS cases. CYC1 immunoreactivity was detected in 40% of DCIS cases, and the immunohistochemical CYC1 status was significantly associated with tumor size, nuclear grade, comedo necrosis, van Nuys classification, and Ki-67 labeling index. Subsequent in vitro studies indicated that CYC1 was significantly associated with mitochondrial membrane potential in MCF10DCIS.com DCIS cells. Moreover, CYC1 significantly promoted proliferation activity of MCF10DCIS.com cells and the cells transfected with CYC1 siRNA decreased pro-apoptotic caspase 3 activity under hypoxic or anoxic conditions. Considering that the center of DCIS is poorly oxygenated, these results indicate that CYC1 plays important roles in cell proliferation and comedo necrosis through the elevated oxidative phosphorylation activity in human DCIS. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Magnetic Resonance Imaging in the Evaluation of Ductal Carcinoma In Situ

    PubMed Central

    2010-01-01

    Before 2000, breast magnetic resonance imaging (MRI) was considered a relatively poor imaging tool for ductal carcinoma in situ (DCIS), as a high percentage of false-negative magnetic resonance examinations were cases of DCIS. Three specific shifts in breast MRI occurred, which changed this assessment: 1) a shift from high temporal to high spatial imaging, revealing specific morphological features on MRI suspicious for DCIS; 2) a shift from diagnostic studies of patients with cancers identified on mammography to screening studies of high-risk patients, allowing more accurate comparisons of mammography vs MRI in detecting the full spectrum of breast cancers regardless of appearance on mammography; and 3) a shift from emphasis on masses to improved understanding of features of non–mass-like malignant lesions, distinct from benign background parenchymal enhancement patterns. Over the last decade, research has confirmed that of all imaging tools, MRI has the highest sensitivity in detection of DCIS (compared with mammography and ultrasound). Future studies are needed to clarify how best to use this tool for improved patient outcomes. PMID:20956821

  8. Magnetic resonance imaging in the evaluation of ductal carcinoma in situ.

    PubMed

    Lehman, Constance D

    2010-01-01

    Before 2000, breast magnetic resonance imaging (MRI) was considered a relatively poor imaging tool for ductal carcinoma in situ (DCIS), as a high percentage of false-negative magnetic resonance examinations were cases of DCIS. Three specific shifts in breast MRI occurred, which changed this assessment: 1) a shift from high temporal to high spatial imaging, revealing specific morphological features on MRI suspicious for DCIS; 2) a shift from diagnostic studies of patients with cancers identified on mammography to screening studies of high-risk patients, allowing more accurate comparisons of mammography vs MRI in detecting the full spectrum of breast cancers regardless of appearance on mammography; and 3) a shift from emphasis on masses to improved understanding of features of non-mass-like malignant lesions, distinct from benign background parenchymal enhancement patterns. Over the last decade, research has confirmed that of all imaging tools, MRI has the highest sensitivity in detection of DCIS (compared with mammography and ultrasound). Future studies are needed to clarify how best to use this tool for improved patient outcomes.

  9. A new cell line (8701-BC) from primary ductal infiltrating carcinoma of human breast.

    PubMed Central

    Minafra, S.; Morello, V.; Glorioso, F.; La Fiura, A. M.; Tomasino, R. M.; Feo, S.; McIntosh, D.; Woolley, D. E.

    1989-01-01

    A cell line, designated 8701-BC, was established in culture from tissue fragments of primary ductal infiltrating carcinoma of human breast. The cell cultures after the sixth passage were devoid of contaminating fibroblasts as judged by the positive staining of all cells with the specific epithelial cell markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and cytokeratin 8. The epithelial nature of these cells was confirmed by ultrastructural analyses which demonstrated the retention of specific structural properties characteristic of the original tumour. The cells possessed an abnormal karyotype with 55-60 chromosomes per cell with numerous rearrangements. They do not express HLA antigens and the c-myc gene was not amplified. The 8701-BC cells have a doubling time of approx. 29h and have been maintained in culture for more than 100 passages. These properties suggest the establishment of a human neoplastic cell line which, with its ability to produce homotrimer collagen in vitro, will provide a useful model system for the study of tumour cell:stromal matrix interactions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8 PMID:2548558

  10. Ductal carcinoma in situ of the male breast. Analysis of 31 cases.

    PubMed

    Cutuli, B; Dilhuydy, J M; De Lafontan, B; Berlie, J; Lacroze, M; Lesaunier, F; Graic, Y; Tortochaux, J; Resbeut, M; Lesimple, T; Gamelin, E; Campana, F; Reme-Saumon, M; Moncho-Bernier, V; Cuilliere, J C; Marchal, C; De Gislain, G; N'Guyen, T D; Teissier, E; Velten, M

    1997-01-01

    From 1970 to 1992, 31 pure ductal carcinoma in situ (DCIS) of the male breast treated in 19 French Regional Cancer Centres were reviewed. They represent 5% of all breast cancers treated in men in the same period. The median age was 58 years, but 6 patients were younger than 40 years. TNM classification (UICC, 1978) showed 12 T0 (discovered only by bloody nipple discharge), 10 T1, 5 T2 and four unclassified tumours (Tx). 11 patients (35.5%) had clinical gynecomastia, and three (10%) had a family history of breast cancer. 6 patients underwent lumpectomy, and 25 mastectomy. Axillary dissection was performed in 19 cases. 6 cases received postoperative irradiation. 15 out of 31 lesions were of the papillary subtype, pure or associated with a cribriform component. The size of the 12 measured lesions varied from 3 to 45 mm. All lymph nodes sampled were negative. With a median follow-up of 83 months, 4 patients (13%) presented a local relapse (LR), respectively, at 12, 27, 36 and 55 months. 3 of these patients had been initially treated by lumpectomy. In one case LR was still in situ, but already infiltrating in the 3 others. Radical salvage surgery was performed in 3 cases, but one patient developed metastases and died 30 months later. The last patient was treated by multiple local excisions and tamoxifen. One 43-year-old patient developed a contralateral DCIS and three others developed a metachronous cancer. The aetiology and risk factors of male breast cancer remain unknown. Gynecomastia, which implies an imbalance between androgen and oestrogen, may be a predisposing factor. As in women, DCIS in the male breast has a good prognosis. Total mastectomy without axillary dissection is the basic treatment. Frequently, the first symptom is a bloody nipple discharge. The age of occurrence is younger than for infiltrating carcinoma, suggesting that DCIS is the first step in the development of breast cancer.

  11. Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study.

    PubMed

    Solin, Lawrence J; Gray, Robert; Hughes, Lorie L; Wood, William C; Lowen, Mary Ann; Badve, Sunil S; Baehner, Frederick L; Ingle, James N; Perez, Edith A; Recht, Abram; Sparano, Joseph A; Davidson, Nancy E

    2015-11-20

    To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians. © 2015 by American Society of Clinical Oncology.

  12. The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and is required to sustain FAK steady state levels in breast cancer epithelial cells.

    PubMed

    Bosch, Almudena; Panoutsopoulou, Konstantina; Corominas, Josep Maria; Gimeno, Ramón; Moreno-Bueno, Gema; Martín-Caballero, Juan; Morales, Saleta; Lobato, Tania; Martínez-Romero, Carles; Farias, Eduardo F; Mayol, Xavier; Cano, Amparo; Hernández-Muñoz, Inmaculada

    2014-04-30

    In early stages of metastasis malignant cells must acquire phenotypic changes to enhance their migratory behavior and their ability to breach the matrix surrounding tumors and blood vessel walls. Epigenetic regulation of gene expression allows the acquisition of these features that, once tumoral cells have escape from the primary tumor, can be reverted. Here we report that the expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral cells that invade the stroma in human ductal breast carcinoma and its expression is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer cell lines revealed that Ring1B is required to sustain Fak expression in basal conditions as well as in Tgfβ-treated cells. Functionally, endogenous Ring1B is required for cell migration and invasion in vitro and for in vivo invasion of the mammary fat pad by tumoral cells. Finally we identify p63 as a target of Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63 expression, which in turns represses Fak expression. Importantly, Fak downregulation upon Ring1B depletion is dependent on p63 expression. Our findings provide new insights in the biology of the breast carcinoma and open new avenues for breast cancer prognosis and therapy.

  13. The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and is required to sustain FAK steady state levels in breast cancer epithelial cells

    PubMed Central

    Bosch, Almudena; Panoutsopoulou, Konstantina; Corominas, Josep Maria; Gimeno, Ramón; Moreno-Bueno, Gema; Martín-Caballero, Juan; Morales, Saleta; Lobato, Tania; Martínez-Romero, Carles; Farias, Eduardo F.; Mayol, Xavier; Cano, Amparo; Hernández-Muáoz, Inmaculada

    2014-01-01

    In early stages of metastasis malignant cells must acquire phenotypic changes to enhance their migratory behavior and their ability to breach the matrix surrounding tumors and blood vessel walls. Epigenetic regulation of gene expression allows the acquisition of these features that, once tumoral cells have escape from the primary tumor, can be reverted. Here we report that the expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral cells that invade the stroma in human ductal breast carcinoma and its expression is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer cell lines revealed that Ring1B is required to sustain Fak expression in basal conditions as well as in Tgfβ-treated cells. Functionally, endogenous Ring1B is required for cell migration and invasion in vitro and for in vivo invasion of the mammary fat pad by tumoral cells. Finally we identify p63 as a target of Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63 expression, which in turns represses Fak expression. Importantly, Fak downregulation upon Ring1B depletion is dependent on p63 expression. Our findings provide new insights in the biology of the breast carcinoma and open new avenues for breast cancer prognosis and therapy. PMID:24742605

  14. Invasive micropapillary carcinoma: A distinct type of adenocarcinomas in the gastrointestinal tract

    PubMed Central

    Guzińska-Ustymowicz, Katarzyna; Niewiarowska, Katarzyna; Pryczynicz, Anna

    2014-01-01

    Invasive micropapillary carcinoma (IMPC) is a rare histological type of tumor, first described in invasive ductal breast cancer, than in malignancies in other organs such as lungs, urinary bladder, ovaries or salivary glands. Recent literature data shows that this histological lesion has also been found in cancers of the gastrointestinal system. The micropapillary components are clusters of neoplastic cells that closely adhere to each other and are located in distinct empty spaces. Moreover, clusters of neoplastic cells do not have a fibrous-vascular core. The IMPC cells show reverse polarity resulting in typical ‘’inside-out’’ structures that determines secretary properties, disturbs adhesion and conditions grade of malignancy in gastrointestinal (GI) tract. Invasive micropapillary carcinoma in this location is associated with metastases to local lymph nodes and lymphovascular invasion. IMPC can be a prognostic factor for patients with cancers of the stomach, pancreas and with colorectal cancer since it is related with disease-free and overall survival. The purpose of this review is to present the characterization of invasive micropapillary carcinoma in colon, rectum, stomach and others site of GI tract, and to determine the immunohistological indentification of IMPC in those localization. PMID:24782612

  15. Investigating Ductal Carcinoma in Situ Using Noninvasive Imaging of Genetically Engineered Mouse Models

    DTIC Science & Technology

    2013-08-01

    LaMarca H, Edwards D, Kerbawy S, Heestand JC, Young E, Mukhopadhyay P, Yeh HW, Allred DC, Hu M, Polyak K, Rosen JM, Medina D. An intraductal human...2010 134-8. Behbod F, Kittrell F S, Lamarca H, Edwards D, Kerbawy S, Heestand J C, Young E, Mukhopadhyay P, Yeh H W, Allred D C, Hu M, Polyak K, Rosen...Bauerlein E L, Hahn W C, Gelman R S, Allred C, Bissell M J, Schnitt S and Polyak K 2008 Regulation of in situ to invasive breast carcinoma

  16. PS2-33: Incidence and Treatment of Ductal Carcinoma in Situ in Kaiser Permanente, 2000–2010

    PubMed Central

    Carroll, Nikki; Weinmann, Sheila; Habel, Laurel; Haque, Reina; Butler, Melissa; Waitzfelder, Beth; Chu-Ling, Yu; Wrenn, Michelle; Bachman, Don; McGlynn, Elizabeth; Feigelson, Heather

    2014-01-01

    Background/Aims Ductal carcinoma in situ (DCIS) makes up approximately 25% of all breast cancer diagnoses and is considered to be a precursor to invasive cancer. Most DCIS diagnoses will not progress to invasive cancer, but reliable prognostic and predictive markers to guide treatment have not been established. Considerable debate exists about how to best treat DCIS, and many have expressed concern that DCIS is over-diagnosed and over-treated. This study examined patterns of DCIS incidence and treatment across six regions of Kaiser Permanente (KP). Methods Women aged ≥ 18 years of age diagnosed with DCIS between 2000 and 2010 were identified from tumor registries at each region using distributed code. Annual age-adjusted incidence rates of DCIS were estimated overall and by region and were standardized to the 2000 US population. The annual incidence of DCIS was also estimated for women aged ≥ 45 years and stratified on hormone replacement therapy status at DCIS diagnosis. Demographic characteristics and variation in first course of therapy were compared. Results Across six KP regions, overall age-adjusted incidence was 35.2/100,000 in 2000, increased to a high of 47.2/100,000 in 2007, and then decreased to 42.6/100,000 in 2010. Age-adjusted incidence rates for women on estrogen plus progestin hormone therapy prior to diagnosis were higher than for women on estrogen only or no hormone therapy. The most common first course therapy was breast conserving surgery plus radiation (38%); however, we observed different treatment patterns across regions. These patterns will be explored further in additional analyses that will include examining variation in treatment patterns by age, year of diagnosis, and histopathologic characteristics such as hormone receptor status and tumor grade. Conclusions Although age-adjusted incidence rates from six KP regions were consistent over time, we observed differences in treatment patterns. Differences in patient mix, tumor

  17. Conservative treatment of breast ductal carcinoma in situ: results of an Italian multi-institutional retrospective study.

    PubMed

    Vidali, Cristiana; Caffo, Orazio; Aristei, Cynthia; Bertoni, Filippo; Bonetta, Alberto; Guenzi, Marina; Iotti, Cinzia; Leonardi, Maria Cristina; Mussari, Salvatore; Neri, Stefano; Pietta, Nicoletta

    2012-10-25

    The incidence of ductal carcinoma in situ (DCIS) has increased markedly in recent decades. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery followed by radiation therapy (RT) has become the standard approach. We present the final results of a multi-institutional retrospective study of an Italian Radiation Oncology Group for the study of conservative treatment of DCIS, characterized by a very long period of accrual, from February 1985 to March 2000, and a median follow-up longer than 11 years. A collaborative multi-institutional study was conducted in Italy in 10 Radiation Oncology Departments. A consecutive series of 586 women with DCIS histologically confirmed, treated between February 1985 and March 2000, was retrospectively evaluated. Median age at diagnosis was 55 years (range: 29-84); 32 patients were 40 years old or younger. All women underwent conservative surgery followed by whole breast RT. Irradiation was delivered to the entire breast, for a median total dose of 50 Gy; the tumour bed was boosted in 295 cases (50%) at a median dose of 10 Gy. After a median follow-up of 136 months (range: 16-292 months), 59/586 patients (10%) experienced a local recurrence: invasive in 37 cases, intraductal in 20 and not specified in two. Salvage mastectomy was the treatment of choice in 46 recurrent patients; conservative surgery in 10 and it was unknown in three patients. The incidence of local recurrence was significantly higher in women younger than 40 years (31.3%) (p= 0.0009). Five patients developed distant metastases. Furthermore 40 patients developed a contralateral breast cancer and 31 a second primary tumour in a different site. The 10-year actuarial overall survival (OS) was 95.5% and the 10-year actuarial disease-specific survival (DSS) was 99%. Our results are consistent with those reported in the literature. In particular it has been defined the importance of young age (40 years

  18. Conservative treatment of breast ductal carcinoma in situ: results of an Italian multi-institutional retrospective study

    PubMed Central

    2012-01-01

    Background The incidence of ductal carcinoma in situ (DCIS) has increased markedly in recent decades. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery followed by radiation therapy (RT) has become the standard approach. We present the final results of a multi-institutional retrospective study of an Italian Radiation Oncology Group for the study of conservative treatment of DCIS, characterized by a very long period of accrual, from February 1985 to March 2000, and a median follow-up longer than 11 years. Methods A collaborative multi-institutional study was conducted in Italy in 10 Radiation Oncology Departments. A consecutive series of 586 women with DCIS histologically confirmed, treated between February 1985 and March 2000, was retrospectively evaluated. Median age at diagnosis was 55 years (range: 29–84); 32 patients were 40 years old or younger. All women underwent conservative surgery followed by whole breast RT. Irradiation was delivered to the entire breast, for a median total dose of 50 Gy; the tumour bed was boosted in 295 cases (50%) at a median dose of 10 Gy. Results After a median follow-up of 136 months (range: 16–292 months), 59/586 patients (10%) experienced a local recurrence: invasive in 37 cases, intraductal in 20 and not specified in two. Salvage mastectomy was the treatment of choice in 46 recurrent patients; conservative surgery in 10 and it was unknown in three patients. The incidence of local recurrence was significantly higher in women younger than 40 years (31.3%) (p= 0.0009). Five patients developed distant metastases. Furthermore 40 patients developed a contralateral breast cancer and 31 a second primary tumour in a different site. The 10-year actuarial overall survival (OS) was 95.5% and the 10-year actuarial disease-specific survival (DSS) was 99%. Conclusions Our results are consistent with those reported in the literature. In particular it has been

  19. Proteomic analysis of infiltrating ductal carcinoma tissues by coupled 2-D DIGE/MS/MS analysis.

    PubMed

    Davalieva, K; Kiprijanovska, S; Broussard, C; Petrusevska, G; Efremov, G D

    2012-01-01

    There is a growing interest in protein expression profiling aiming to identify novel diagnostic markers in breast cancer. Proteomic approaches such as two-dimensional differential gel electrophoresis coupled with tandem mass spectrometry analysis (2-D DIGE/MS/MS) have been used successfully for the identification of candidate biomarkers for screening, diagnosis, prognosis and monitoring of treatment response in various types of cancer. Identifying previously unknown proteins of potential clinical relevance will ultimately help in reaching effective ways to manage the disease. We analyzed breast cancer tissues from five tumor and five normal tissue samples from ten breast cancer subjects with infiltrating ductal carcinoma (IDC) by 2-D DIGE using two types of immobilized pH gradient (IPG) strips: pH 3-10 and pH 4-7. From all the spots detected, differentially expressed (p < 0.05 and ratio > 2) were 50 spots. Of these, 39 proteins were successfully identified by MS, representing 29 different proteins. Ten proteins were overexpressed in the tumor samples. The 2-D DIGE/MS/MS analysis revealed an increase in the expression levels in tumor samples of several proteins not previously associated with breast cancer, such as: macrophage-capping protein (CAPG), phosphomannomutase 2 (PMM2), ATPase ASN1, methylthioribose-1-phosphate isomerase (MRI1), peptidyl-prolyl cis-trans isomerase FKBP4, cellular retinoic acid-binding protein 2 (CRABP2), lamin B1 and keratin, type II cytoskeletal 8 (KRT8). Ingenuity Pathway Analysis (IPA) revealed highly significant (p = 10(-26)) interactions between the identified proteins and their association with cancer. These proteins are involved in many diverse pathways and have established roles in cellular metabolism. It remains the goal of future work to test the suitability of the identified proteins in samples of larger and independent patient groups.

  20. Rates of Second Malignancies After Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast

    SciTech Connect

    Shaitelman, Simona F.; Grills, Inga S.; Kestin, Larry L.; Ye Hong; Nandalur, Sirisha; Huang Jiayi; Vicini, Frank A.

    2011-12-01

    Purpose: We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone. Methods and Materials: The S+RT cohort consisted of 256 women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age {+-} 2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system. Results: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p = 0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p = 0.439). The 15-year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p = 0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. Conclusions: Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS.

  1. Adjuvant Hormonal Therapy Use Among Women with Ductal Carcinoma In Situ

    PubMed Central

    Livaudais, Jennifer C.; Hwang, E. Shelley; Karliner, Leah; Nápoles, Anna; Stewart, Susan; Bloom, Joan

    2012-01-01

    Abstract Objective In the absence of consistent guidelines for the use of adjuvant hormonal therapy (HT) in treating ductal carcinoma in situ (DCIS), our purpose was to explore a variety of factors associated with discussion, use, and discontinuation of this therapy for DCIS, including patient, tumor, and treatment-related characteristics and physician-patient communication factors. Methods We identified women from eight California Cancer Registry regions diagnosed with DCIS from 2002 through 2005, aged ≥18 years, of Latina or non-Latina white race/ethnicity. A total of 744 women were interviewed an average of 24 months postdiagnosis about whether they had (1) discussed with a physician, (2) used, and (3) discontinued adjuvant HT. Results Although 83% of women discussed adjuvant HT with a physician, 47% used adjuvant HT, and 23% of users reported discontinuation by a median of 11 months. In multivariable adjusted analyses, Latina Spanish speakers were less likely than white women to discuss therapy (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.18-0.69) and more likely to discontinue therapy (OR 2.67, 95% CI 1.05-6.81). Seeing an oncologist for follow-up care was associated with discussion (OR 5.10, 95% CI 3.14-8.28) and use of therapy (OR 4.20, 95% CI 2.05-8.61). Similarly, physician recommendation that treatment was necessary vs. optional was positively associated with use (OR 11.2, 95% CI 6.50-19.4) and inversely associated with discontinuation (OR 0.38, 95% CI 0.19-0.73). Conclusions Physician recommendation is an important factor associated with use and discontinuation of adjuvant HT for DCIS. Differences in discussion and discontinuation of therapy according to patient characteristics, particularly ethnicity/language, suggest challenges to physician-patient communication about adjuvant HT across a language barrier. PMID:21902542

  2. Reporting the greatest linear extent of ductal carcinoma in situ on needle core biopsy.

    PubMed

    Reisenbichler, Emily S; Hameed, Omar

    2016-04-01

    Ductal carcinoma in situ (DCIS) of the breast is staged as pTis regardless of size; however, extent of DCIS correlates with local recurrence rates and likelihood of close or positive margins. As a result, DCIS extent influences patient management and is an important element in the College of American Pathologists tumor summary checklist for excision specimens. There are no recommendations regarding routine reporting of DCIS extent on needle core biopsy material, and to our knowledge, no systematic studies have evaluated the impact of reporting this in biopsy material. Consecutive cases of DCIS performed or reviewed at our institution were identified by pathology report search over a 7-year period. The greatest linear extent of DCIS on core biopsy was compared with the estimated extent in the excision. Of 241 total cases, there were 157 (65%) cases in which the DCIS extent on biopsy was smaller, 13 (5%) cases in which the sizes were equal, and 70 (29%) cases in which the biopsy size was greater, including 30 (12%) with no residual tumor on excision. Mean extent was greater on excision than on core biopsy (16.0 versus 5.7 mm; P < .0001); however, the opposite was seen when only small tumors (≤ 10 mm final size) were considered (4.5 versus. 3.6 mm; P = .0161). There was strong linear correlation (r = 0.9761; P < .0001) between the size change (excision size minus biopsy size) and final pathologic size. For accurate tumor summary checklist completion, DCIS extent should be reported for needle biopsy material, particularly in the setting of small tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Value of pre-operative breast MRI for the size assessment of ductal carcinoma in situ

    PubMed Central

    Proulx, Francesca; Correa, José A; Ferré, Romuald; Omeroglu, Atilla; Aldis, Ann; Meterissian, Sarkis

    2016-01-01

    Objective: To retrospectively evaluate the accuracy of pre-operative breast MRI and mammography in determining the size of ductal carcinoma in situ (DCIS) compared with the histopathological results. Methods: 79 patients [mean age: 56.5 (standard deviation 10.2) years] with pathologically proven DCIS (79 lesions) obtained a bilateral mammogram and a pre-operative contrast-enhanced MRI. The accuracy of MRI and mammography to detect tumour size were estimated and compared, using histopathological size as the gold standard, on the subjects with measurements with both modalities (n = 60). Results: MRI detected 67 (85%) lesions, mammography detected 72 (91%) and both modalities detected 60 (76%). Median DCIS size detected by mammography vs MRI was smaller (1.55 vs 1.65 cm). Out of these 60 cases, compared with the histopathological size, the accuracy of MRI and mammography was 0.66 and 0.56, respectively (p = 0.045). MRI showed better accuracy than mammography for younger patients (age ≤ 50 years, p = 0.003). For tumour nuclear grade, there was a statistically significant difference for the intermediate level, with higher accuracy for MRI (p = 0.03). Conclusion: MRI was more accurate than mammography in DCIS size assessment when visible, particularly in lesions of intermediate grade and in patients less than 50 years of age. Advances in knowledge: Breast MRI may help in management of DCIS of intermediate grade and in females less than 50 years of age. PMID:26568438

  4. Trends in Health-Related Quality of Life After a Diagnosis of Ductal Carcinoma In Situ

    PubMed Central

    Sprague, Brian L.; Lakoski, Susan G.; Hampton, John M.; Newcomb, Polly A.; Gangnon, Ronald E.; Trentham-Dietz, Amy

    2016-01-01

    Purpose Studies of quality of life (QoL) are scarce among survivors of ductal carcinoma in situ (DCIS). The objective of this study was to assess long-term QoL in DCIS survivors in relation to age at diagnosis, time since diagnosis, and treatments received. Methods We assessed physical and mental measures of health-related QoL in 1,604 patients with DCIS diagnosed in 1997 to 2006 with up to four follow-up interviews. We further compared baseline QoL to 1,055 control patients without DCIS. QoL was measured using the validated Medical Outcomes Study Short Form 36 Health Status Survey questionnaire. Among patients with DCIS, we examined trends in QoL over time since diagnosis using generalized linear regression models, adjusting for confounders. We tested for effect modification by surgical treatment choice, post-treatment endocrine therapy use, and age at diagnosis. Results Both physical and mental measures of QoL among DCIS survivors at fewer than 2 years after diagnosis were comparable to controls. Mental measures of QoL among patients with DCIS declined at ≥ 10 years after diagnosis and were significantly lower than at less than 2 years after diagnosis (47.4 v 52.0; P < .01). In the first 5 years after a DCIS diagnosis, mental QoL was significantly higher among women diagnosed at ages 50 to 74 years compared with those diagnosed at ages 28 to 49 years, although this difference was not sustained in later time periods. Conclusion QoL after a DCIS diagnosis was generally comparable to that of women of similar age without a personal history of DCIS. Our findings suggest that DCIS survivors, and particularly those diagnosed at a younger age, may benefit from support for mental QoL. PMID:26884560

  5. Evaluation of automated breast volume scanner for breast conservation surgery in ductal carcinoma in situ.

    PubMed

    Huang, Anqian; Zhu, Luoxi; Tan, Yanjuan; Liu, Jian; Xiang, Jingjing; Zhu, Qingqing; Bao, Lingyun

    2016-10-01

    The present is a retrospective study examining the use of automated breast volume scanner (ABVS) for guiding breast conservation surgery in ductal carcinoma in situ (DCIS). A total of 142 patients with pathologically confirmed DCIS were initially included in the study. The patients underwent preoperative examination by conventional ultrasound and by ABVS. The BI-RADS category system was used to identify benign and malignant lesions, after which breast conservation surgery was performed, and the therapeutic effects were compared. DCIS lesions were found in each quadrant of the breasts. Typical symptoms included: Duct ectasia and filling in 23 cases, mass (mainly solid, occasionally cystic, with or without calcification) in 38 cases, hypoechoic area (with or without calcification) in 33 cases, calcifications (simple) in 23 cases, and architectural distortion in 17 cases. In addition, 110 cases (82.1%) were detected as grade ≥4 according to the BI-RADS category, and 92 cases (68.7%) were considered malignant lesions following conventional ultrasound scanning. The detection rate of ABVS was significantly higher than that of conventional ultrasound (χ(2)=268.000, P<0.001). The average tumor diameter was 2.5±0.8 cm using ABVS and 2.0±0.9 cm using conventional ultrasound (the former being significantly higher than the latter; t=6.325, P=0.034). Eight patients (5.6%) had recurrences of the cancer, and the tumor diameter in the 8 patients was significantly larger using ABVS as compared to conventional ultrasound. In the diagnosis of DCIS, ABVS was superior to conventional ultrasound scanner in guiding breast conservation surgery and predicting recurrence. However, large-scale studies are required for confirmation of the findings.

  6. Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

    PubMed

    Thomas, Jeremy; Hanby, Andrew; Pinder, Sarah E; Ball, Graham; Lawrence, Gill; Maxwell, Anthony; Wallis, Matthew; Evans, Andrew; Dobson, Hilary; Clements, Karen; Thompson, Alastair

    2014-07-01

    The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. International variation in management of screen-detected ductal carcinoma in situ of the breast

    PubMed Central

    Ponti, Antonio; Lynge, Elsebeth; James, Ted; Májek, Ondřej; von Euler-Chelpin, My; Anttila, Ahti; Fitzpatrick, Patricia; Mano, Maria Piera; Kawai, Masaaki; Scharpantgen, Astrid; Fracheboud, Jacques; Hofvind, Solveig; Vidal, Carmen; Ascunce, Nieves; Salas, Dolores; Bulliard, Jean-Luc; Segnan, Nereo; Kerlikowske, Karla; Taplin, Stephen

    2014-01-01

    Background Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. Methods We sought screen-detected DCIS data from the ICSN countries identified during 2004–2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. Results Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50–69 years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67–90% of DCIS received breast conservation surgery (BCS), and in 41–100% of the cases this was followed by radiotherapy; 6.4–59% received sentinel lymph node biopsy (SLNB) only and 0.8–49% axillary dissection (ALND) with 0.6% (range by programmes 0–8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. Conclusions Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction. PMID:25149183

  8. Detection of Ductal Carcinoma In Situ by Ultrasound and Mammography: Size-dependent Inaccuracy.

    PubMed

    Eichler, Christian; Abrar, Sharareh; Puppe, Julian; Arndt, Mariam; Ohlinger, Ralf; Hahn, Markus; Warm, Mathias

    2017-09-01

    Retrospective analysis of breast cancer imaging methods is a common tool for evaluating the effectiveness of ultrasound and mammography regarding ductal carcinoma in situ (DCIS). No large number subpopulation of pure DCIS has been reported. It is however known that mammography and ultrasound underestimate tumor dimension with increasing tumor size. We aimed to quantify this discrepancy. This retrospective analysis reviewed the ultrasound and mammography data from 173 patients with DCIS at the University of Cologne - Department of Gynecology and Obstetrics between the years 2007 and 2010. Of these 173 patients, 34 fulfilled the DCIS analysis requirements and were evaluated in this study. Overall, ultrasound underestimated tumor size 79.4% of the time, while overestimating only 20.6% of the time. Mammography underestimated tumor size in 50%, overestimated in 38.2%, correctly estimating in 11.8%. Over and underestimation distributions differed drastically above and a cut-off point of ≤2 cm actual tumor size, with a significant shift toward severe underestimation by both methods above a tumor size of 2 cm. DCIS misestimation was defined as the absolute value of the difference between actual tumor size and pre-surgical measurement by an imaging method. Mean DCIS size misestimation (actual tumor size ≤2 cm) was 3 mm for ultrasound and 6.2 mm for mammography. We support previous findings that ultrasound and mammography lose accuracy with increasing tumor size. Nonetheless, ultrasound may be more useful in estimation of DCIS size for tumors ≤2 cm than previously expected. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Treatment of Ductal Carcinoma In Situ Among Patients Cared for in Large Integrated Health Plans

    PubMed Central

    Haque, Reina; Achacoso, Ninah S.; Fletcher, Suzanne W.; Nekhlyudov, Larissa; Collins, Laura C.; Schnitt, Stuart J.; Quesenberry, Charles P.; Habel, Laurel A.

    2013-01-01

    Objective To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. Study Design Cross-sectional study nested within a cohort of women diagnosed as having DCIS between 1990 and 2001. Methods We reviewed medical records of 3000 non-Hispanic white (69%), black (10%), Hispanic (9%), and Asian or Pacific Islander (12%) women diagnosed as having DCIS between 1990 and 2001 and treated with breast-conserving therapy. χ2 Test and multinomial logistic regression analysis were used to examine the association between race/ethnicity and use of adjuvant treatments after controlling for patient and clinical variables, including certain pathologic factors. Results We found no significant differences in DCIS adjuvant treatment among racial/ethnic groups in bivariate or multinomial analyses after adjusting for demographic characteristics, comorbidity, and clinical factors. Minority women were as likely to undergo adjuvant radiation therapy as non-Hispanic white women. However, women 70 years or older (odds ratio, 0.40; 95% confidence interval, 0.31–0.51) and women who lived in areas with low geocoded median family income (odds ratio, 0.65; 95% confidence interval, 0.48–0.89) were less likely to receive adjuvant radiation therapy. Tumor size and comedo histologic growth pattern were associated with increased likelihood of receiving radiation therapy. Conclusion Use of adjuvant therapy by minority women in these managed care plans is similar to that by non-Hispanic white women, although use was less among older women and among women who lived in poorer neighborhoods. PMID:20469955

  10. Ductal Carcinoma in Situ-The Influence of the Radiotherapy Boost on Local Control

    SciTech Connect

    Wong, Philip; Lambert, Christine; Agnihotram, Ramanakumar V.; David, Marc; Duclos, Marie; Freeman, Carolyn R.

    2012-02-01

    Purpose: Local recurrence (LR) of ductal carcinoma in situ (DCIS) is reduced by whole-breast irradiation after breast-conserving surgery (BCS). However, the benefit of adding a radiotherapy boost to the surgical cavity for DCIS is unclear. We sought to determine the impact of the boost on LR in patients with DCIS treated at the McGill University Health Centre. Methods and Materials: A total of 220 consecutive cases of DCIS treated with BCS and radiotherapy between January 2000 and December 2006 were reviewed. Of the patients, 36% received a radiotherapy boost to the surgical cavity. Median follow-up was 46 months for the boost and no-boost groups. Kaplan-Meier survival analyses and Cox regression analyses were performed. Results: Compared with the no-boost group, patients in the boost group more frequently had positive and <0.1-cm margins (48% vs. 8%) (p < 0.0001) and more frequently were in higher-risk categories as defined by the Van Nuys Prognostic (VNP) index (p = 0.006). Despite being at higher risk for LR, none (0/79) of the patients who received a boost experienced LR, whereas 8 of 141 patients who did not receive a boost experienced an in-breast LR (log-rank p = 0.03). Univariate analysis of prognostic factors (age, tumor size, margin status, histological grade, necrosis, and VNP risk category) revealed only the presence of necrosis to significantly correlate with LR (log-rank p = 0.003). The whole-breast irradiation dose and fractionation schedule did not affect LR rate. Conclusions: Our results suggest that the use of a radiotherapy boost improves local control in DCIS and may outweigh the poor prognostic effect of necrosis.

  11. Evaluation of automated breast volume scanner for breast conservation surgery in ductal carcinoma in situ

    PubMed Central

    Huang, Anqian; Zhu, Luoxi; Tan, Yanjuan; Liu, Jian; Xiang, Jingjing; Zhu, Qingqing; Bao, Lingyun

    2016-01-01

    The present is a retrospective study examining the use of automated breast volume scanner (ABVS) for guiding breast conservation surgery in ductal carcinoma in situ (DCIS). A total of 142 patients with pathologically confirmed DCIS were initially included in the study. The patients underwent preoperative examination by conventional ultrasound and by ABVS. The BI-RADS category system was used to identify benign and malignant lesions, after which breast conservation surgery was performed, and the therapeutic effects were compared. DCIS lesions were found in each quadrant of the breasts. Typical symptoms included: Duct ectasia and filling in 23 cases, mass (mainly solid, occasionally cystic, with or without calcification) in 38 cases, hypoechoic area (with or without calcification) in 33 cases, calcifications (simple) in 23 cases, and architectural distortion in 17 cases. In addition, 110 cases (82.1%) were detected as grade ≥4 according to the BI-RADS category, and 92 cases (68.7%) were considered malignant lesions following conventional ultrasound scanning. The detection rate of ABVS was significantly higher than that of conventional ultrasound (χ2=268.000, P<0.001). The average tumor diameter was 2.5±0.8 cm using ABVS and 2.0±0.9 cm using conventional ultrasound (the former being significantly higher than the latter; t=6.325, P=0.034). Eight patients (5.6%) had recurrences of the cancer, and the tumor diameter in the 8 patients was significantly larger using ABVS as compared to conventional ultrasound. In the diagnosis of DCIS, ABVS was superior to conventional ultrasound scanner in guiding breast conservation surgery and predicting recurrence. However, large-scale studies are required for confirmation of the findings. PMID:27698816

  12. Prospective Multicenter Trial Evaluating Balloon-Catheter Partial-Breast Irradiation for Ductal Carcinoma in Situ

    SciTech Connect

    Abbott, Andrea M.; Portschy, Pamela R.; Lee, Chung; Le, Chap T.; Han, Linda K.; Washington, Tara; Kinney, Michael; Bretzke, Margit; Tuttle, Todd M.

    2013-11-01

    Purpose: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. Methods and Materials: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results: A total of 41 patients (42 breasts) completed treatment in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. Conclusions: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended.

  13. Correlation of clinicopathologic parameters and immunohistochemical features of triple-negative invasive lobular carcinoma.

    PubMed

    Harbhajanka, Aparna; Lamzabi, Ihab; Singh, Rohit I; Ghai, Ritu; Reddy, Vijaya B; Bitterman, Pincas; Gattuso, Paolo

    2014-07-01

    Invasive lobular carcinoma (ILC) is a subtype of invasive breast carcinoma. With the advent of gene profiling, breast cancer has been classified into luminal A, luminal B, HER2-overexpressing, and triple-negative carcinoma (TNC). Several studies have described TNC (ER, PR, HER2) as a surrogate for basal-like breast carcinoma. However, there is sparse literature on triple-negative lobular carcinoma (TNLC), as most of them show hormone receptor expression. The aim of this study was to investigate the correlation of clinicopathologic parameters of TNLC that has been demonstrated in invasive ductal carcinoma. Clinicopathologic parameters and immunohistochemical stains for ER, PR, E-cadherin, HER2, MIB1, and fluorescent in situ hybridization for HER2 of 255 ILC cases were retrieved. In addition, immunohistochemical analysis was performed for p53, c-kit, vimentin, p16, cyclinD1, and BCL2 on 78 cases where 12 were TNC cases and 66 were non-TNC cases. Of the 255 ILC cases, 218 (85.5%) were classic and 37 (14.5%) were pleomorphic. Seventy-seven (30.1%) cases showed axillary lymph node metastasis. There were 14 of the 255 TNC cases (5.49%) that showed higher incidence in the elderly patients. Six of the 37 (16.21%) cases were pleomorphic and 8 of the 218 (3.7%) cases were classic. Positivity for vimentin was seen in 8 of the 12 cases (67.7%), CK 5 in 3 of the 12 (25%) cases, p16 in 11 of the 12 (91.6%) cases, p53 in 8 of the 12 (66.7%) cases, c-kit in 6 of the 12 (50%) cases, and cyclinD1 in 6 of the 12 cases (50%) indicating basal-like phenotype in 3 cases and nonbasal-like phenotype in 9 cases. There was no statistical significance in lymph node metastasis, tumor recurrence, and distant metastasis between TNC and non-TNC. TNLC showed distinct clinicopathologic features such as more frequently seen in the elderly, pleomorphic, larger tumor size, increased expression of vimentin, CK 5, p16, p53, and c-kit. Not all cases showed basal-like phenotype. TNLC is less frequently

  14. The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer.

    PubMed

    Gujam, F J A; McMillan, D C; Mohammed, Z M A; Edwards, J; Going, J J

    2015-09-29

    Tumour budding has previously been reported to predict survival in several solid organ tumours, including breast; however, whether this is independent of other aspects of the tumour microenvironment is unknown. In the present study, the relationship between tumour budding, the tumour microenvironment and survival was examined in patients with invasive ductal breast cancer. Patients presenting between 1995 and 1998 were studied (n=474). Using routine pathological sections, tumour budding was measured at the invasive margin and its association with clinicopathological characteristics and cancer-specific survival (CSS) was examined. Tumour budding was associated with several adverse pathological characteristics, including lymph node involvement, lymph vessel invasion (LVI), increased tumour stroma percentage (TSP) and weaker local inflammatory infiltrative. Tumour budding was associated with reduced CSS (hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.14-3.09, P=0.004), independent of nodal status, molecular subtypes, tumour necrosis, CD8+, CD138+, LVI, blood vessel invasion and TSP. Further, tumour budding was independently associated with reduced CSS in node-negative patients (HR 2.63, 95% CI 1.16-5.92, P=0.020) and those who have low TSP (HR 1.98, 95% CI 1.09-3.57, P=0.024) and high-grade local inflammatory infiltrative (HR 2.27, 95% CI 1.35-5.36, P=0.014). Tumour budding was a significant predictor of survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. The present study further confirms the clinical utility of both tumour and host-based factors of tumour microenvironment.

  15. The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer

    PubMed Central

    Gujam, F J A; McMillan, D C; Mohammed, Z M A; Edwards, J; Going, J J

    2015-01-01

    Background: Tumour budding has previously been reported to predict survival in several solid organ tumours, including breast; however, whether this is independent of other aspects of the tumour microenvironment is unknown. In the present study, the relationship between tumour budding, the tumour microenvironment and survival was examined in patients with invasive ductal breast cancer. Methods: Patients presenting between 1995 and 1998 were studied (n=474). Using routine pathological sections, tumour budding was measured at the invasive margin and its association with clinicopathological characteristics and cancer-specific survival (CSS) was examined. Results: Tumour budding was associated with several adverse pathological characteristics, including lymph node involvement, lymph vessel invasion (LVI), increased tumour stroma percentage (TSP) and weaker local inflammatory infiltrative. Tumour budding was associated with reduced CSS (hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.14–3.09, P=0.004), independent of nodal status, molecular subtypes, tumour necrosis, CD8+, CD138+, LVI, blood vessel invasion and TSP. Further, tumour budding was independently associated with reduced CSS in node-negative patients (HR 2.63, 95% CI 1.16–5.92, P=0.020) and those who have low TSP (HR 1.98, 95% CI 1.09–3.57, P=0.024) and high-grade local inflammatory infiltrative (HR 2.27, 95% CI 1.35–5.36, P=0.014). Conclusions: Tumour budding was a significant predictor of survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. The present study further confirms the clinical utility of both tumour and host-based factors of tumour microenvironment. PMID:26263482

  16. Biologic features and prognosis of ductal carcinoma in situ are not adversely impacted by initial large body mass

    PubMed Central

    Lari, Sara A.; Arun, Banu K.; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A.; Albarracin, Constance T.; Babiera, Gildy V.; Caudle, Abigail S.; Wagner, Jamie L.; Litton, Jennifer K.; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K.

    2013-01-01

    Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI 25 to<30 kg/m2), or of normal weight or underweight (BMI <25 kg/m2). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local–regional recurrence was calculated using the Kaplan–Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66–5.80) or Hispanic (OR, 1.44; CI, 1.02–2.04), be postmenopausal (OR, 1.63; CI, 1.28–2.07), have diabetes (OR, 4.60; CI, 2.60–8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00–192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01–1.80). At a median follow-up time of 4.96 years (range, 1.0–14.34 years), no significant differences in local recurrence rates were detected based on patients’ initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS. PMID:22392043

  17. Adjuvant radiotherapy versus observation following lumpectomy in ductal carcinoma in-situ: A meta-analysis of randomized controlled trials.

    PubMed

    Garg, Pankaj Kumar; Jakhetiya, Ashish; Pandey, Rambha; Chishi, Nilokali; Pandey, Durgatosh

    2017-08-22

    The role of adjuvant radiotherapy (RT) following lumpectomy for ductal carcinoma in-situ (DCIS) was addressed in four major randomized controlled trials (RCTs) which were conducted two to three decades ago. Initial results of these trials suggested the protective role of RT in reducing the ipsilateral breast recurrences. Long-term results of all these four trials, based on more than 10-years follow-up data, have recently been published. A meta-analysis of four published RCTs which have addressed the role of adjuvant RT following lumpectomy for DCIS was conducted. Review manager (Cochrane Collaboration's software) version RevMan 5.2 was used for analysis. Evaluated events were ipsilateral breast recurrences (both DCIS and invasive), regional recurrences, contralateral breast events, distant recurrences, and overall mortality. The events were entered as dichotomous variable. The present meta-analysis included four RCTs and a total of 3680 patients - 1710 received adjuvant RT following lumpectomy while 1970 patients did not receive any adjuvant treatment. Patients who received RT had almost half of risk of ipsilateral breast recurrence (RR = 0.53, 95% CI = 0.45-0.62) and regional recurrence (RR = 0.54, 95% CI = 0.32-0.91) compared to those who did not receive adjuvant treatment - there was absolute risk reduction in 15% (95% CI = 12%-17%) for ipsilateral breast recurrences in adjuvant RT treated patients. There was no significant difference in distant recurrence (RR = 1.06, 95% CI = 0.74-1.53), contralateral breast events (RR = 1.22, 95% CI = 0.98-1.52) and overall mortality (RR = 0.93, 95% CI = 0.79-1.09). Though addition of postoperative RT to lumpectomy does not reduce overall mortality, the present meta-analysis confirms that it decreases the ipsilateral breast and regional recurrence by almost half. © 2017 Wiley Periodicals, Inc.

  18. High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast.

    PubMed

    Somiari, Richard I; Sullivan, Anthony; Russell, Stephen; Somiari, Stella; Hu, Hai; Jordan, Rick; George, Alisha; Katenhusen, Richard; Buchowiecka, Alicja; Arciero, Cletus; Brzeski, Henry; Hooke, Jeff; Shriver, Craig

    2003-10-01

    Large-scale proteomics will play a critical role in the rapid display, identification and validation of new protein targets, and elucidation of the underlying molecular events that are associated with disease development, progression and severity. However, because the proteome of most organisms are significantly more complex than the genome, the comprehensive analysis of protein expression changes will require an analytical effort beyond the capacity of standard laboratory equipment. We describe the first high-throughput proteomic analysis of human breast infiltrating ductal carcinoma (IDCA) using OCT (optimal cutting temperature) embedded biopsies, two-dimensional difference gel electrophoresis (2-D DIGE) technology and a fully automated spot handling workstation. Total proteins from four breast IDCAs (Stage I, IIA, IIB and IIIA) were individually compared to protein from non-neoplastic tissue obtained from a female donor with no personal or family history of breast cancer. We detected differences in protein abundance that ranged from 14.8% in stage I IDCA versus normal, to 30.6% in stage IIB IDCA versus normal. A total of 524 proteins that showed > or = three-fold difference in abundance between IDCA and normal tissue were picked, processed and identified by mass spectrometry. Out of the proteins picked, approximately 80% were unambiguously assigned identities by matrix-assisted laser desorbtion/ionization-time of flight mass spectrometry or liquid chromatography-tandem mass spectrometry in the first pass. Bioinformatics tools were also used to mine databases to determine if the identified proteins are involved in important pathways and/or interact with other proteins. Gelsolin, vinculin, lumican, alpha-1-antitrypsin, heat shock protein-60, cytokeratin-18, transferrin, enolase-1 and beta-actin, showed differential abundance between IDCA and normal tissue, but the trend was not consistent in all samples. Out of the proteins with database hits, only heat shock

  19. Inter- and intra-individual variability in somatic allele loss in ductal carcinoma of the breast

    SciTech Connect

    Rebbeck, T.; Godwin, A.; Rosvold, E.

    1994-09-01

    The etiology of most cancers involves both inherited genetic susceptibility and somatic genetic changes. We studied 28 ductal carcinomas of the breast to evaluate variability in loss of constitutional heterozygosity (LOH) across loci and across individuals and to assess the relationship of candidate genes with LOH. LOH was measured on 33 chromosome arms using the most telomeric, highly heterozygous tetranucleotide repeat markers from the Cooperative Human Linkage Center (CHLC). The overall mean proportion of LOH was 11%. The proportion of LOH ranged from 0% to 37% across loci. LOH > 20% was observed at chromosomes 1p, 7q, 10q, 11p, 17p, and 18q. Of these, simultaneous losses at the following locus pairs occurred more often than expected: 1p & 11p; 1p & 17p; 7q & 18q; 11p & 17p. An elevated proportion of LOH was not observed for the marker on chromosome 17q. The proportion of LOH ranged from 0% to 67% across individuals. 20 tumors showed less than 10% LOH, and 6 showed more than 20% LOH. There was no correlation between LOH and tumor stage. To examine whether variability in candidate genes was associated with LOH, allelic variability was measured at CYP1A1, CYP2D6, epoxide hydrolase (EH), HADP(H):quinone oxidoreductase (NQO1), and glutathione-S-transferase-{mu} (GST-{mu}). An elevated proportion of LOH was observed for genotypes at CYP2D6 (17% for 1/1, 1/2`s vs. 8% for 2/2`s), NQO1 (13% for 1/2, 2/2`s vs. 8% for 1/1`s), and GST-{mu} (15% for {open_quotes}null{close_quotes} genotypes vs. 7% for wild types), but not at CYP1A1 (12% for 1/2`s vs. 10% for 1/1`s) or EH (11% for 1/1`s vs. 10% for 1/2`s). Our results suggest that LOH is not randomly distributed across the genome, and that there is substantial interindividual variability in LOH. This interindividual variability may be explained by genes that metabolize environmental carcinogens or steroid hormones.

  20. Cardiovascular Morbidity and Mortality After Treatment for Ductal Carcinoma In Situ of the Breast

    PubMed Central

    Boekel, Naomi B.; Schaapveld, Michael; Gietema, Jourik A.; Rutgers, Emiel J. T.; Versteegh, Michel I. M.; Visser, Otto; Aleman, Berthe M. P.

    2014-01-01

    Background Recent concerns about potential overdiagnosis and overtreatment of ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects of treatment, such as cardiovascular disease (CVD), of great importance. We studied cardiovascular morbidity and mortality in a large population-based cohort of DCIS patients. Methods Data on all incident DCIS case patients in the Netherlands between 1989 and 2004 who were diagnosed before the age of 75 years were obtained (n = 10468). CVD data was acquired through linkage with population-based registries. Standardized mortality ratios were calculated by comparing mortality in our cohort with that in the Dutch female population, taking into account person-years of observation. Within-cohort comparisons were based on multivariable competing-risk regression. Results Compared with the general population, 5-year survivors of DCIS had a similar risk of dying due to any cause (standardized mortality ratio [SMR] = 1.04; 95% confidence interval [CI] = 0.97 to 1.11) but a lower risk of dying of CVD (SMR = 0.77; 95% CI = 0.67 to 0.89). No difference in CVD risk was found when comparing 5-year survivors treated with radiotherapy with those treated with surgery only. Left-sided vs right-sided radiotherapy also did not increase this risk (hazard ratio [HR] = 0.94; 95% CI = 0.67 to 1.32). In a subgroup analysis of all DCIS patients diagnosed between 1997 and 2005, we were able to account for history of CVD and did not observe a risk difference between treatment groups (left-sided vs right-sided radiotherapy: HR = 0.94; 95% CI = 0.68 to 1.29). Conclusions After a median follow-up of 10 years, we did not find an increased risk for cardiovascular morbidity or mortality after radiotherapy for DCIS when comparing surgery and radiotherapy vs surgery only, nor when comparing radiotherapy for left-sided vs right-sided DCIS. Compared with the general population, DCIS patients have a decreased risk of cardiovascular death

  1. Comparative Effectiveness of Ductal Carcinoma In Situ Management and the Roles of Margins and Surgeons

    PubMed Central

    Sorbero, Melony S.; Ahrendt, Gretchen M.; Hayman, James A.; Gold, Heather T.; Schiffhauer, Linda; Stark, Azadeh; Griggs, Jennifer J.

    2011-01-01

    Background The high incidence of ductal carcinoma in situ (DCIS) and variations in its treatment motivate inquiry into the comparative effectiveness of treatment options. Few such comparative effectiveness studies of DCIS, however, have been performed with detailed information on clinical and treatment attributes. Methods We collected detailed clinical, nonclinical, pathological, treatment, and long-term outcomes data from multiple medical records of 994 women who were diagnosed with DCIS from 1985 through 2000 in Monroe County (New York) and the Henry Ford Health System (Detroit, MI). We used ipsilateral disease-free survival models to characterize the role of treatments (surgery and radiation therapy) and margin status (positive, close [<2 mm], or negative [≥2 mm]) and logistic regression models to characterize the determinants of treatments and margin status, including the role of surgeons. All statistical tests were two-sided. Results Treatments and margin status were statistically significant and strong predictors of long-term disease-free survival, but results varied substantially by surgeon. This variation by surgeon accounted for 15%–35% of subsequent ipsilateral 5-year recurrence rates and for 13%–30% of 10-year recurrence rates. The overall differences in predicted 5-year disease-free survival rates for mastectomy (0.993), breast-conserving surgery with radiation therapy (0.945), and breast-conserving surgery without radiation therapy (0.824) were statistically significant (Pdiff < .001 for each of the differences). Similarly, each of the differences at 10 years was statistically significant (P < .001). Conclusions Our work demonstrates the contributions of treatments and margin status to long-term ipsilateral disease-free survival and the link between surgeons and these key measures of care. Although variation by surgeon could be generated by patients’ preferences, the extent of variation and its contribution to long-term health outcomes are

  2. An argument against routine use of radiotherapy for ductal carcinoma in situ.

    PubMed

    Silverstein, Melvin J

    2003-11-01

    Three prospective randomized trials have shown that postexcisional radiation therapy can reduce the relative risk of local recurrence by about 50% in conservatively treated patients with ductal carcinoma in situ (DCIS). In an era of evidence-based medicine, how then can one possibly take a stand against the routine use of radiation therapy after local excision? Surprisingly, the rationale is straightforward. In some low-risk DCIS patients, the costs may far outweigh the potential benefits. In spite of a relative 50% reduction in the probability of local recurrence, the absolute reduction may only be a few percentage points. In addition, the prospective trials focus on local recurrence as their primary end point because it is, by far, the most common untoward event following conservative treatment. Local recurrence is clearly important, but breast cancer-specific survival is, in fact, an even more important end point, and no trial in patients with DCIS has ever shown a survival benefit with the use of radiation. Moreover, radiation therapy is not without financial and physical cost. So, if there is no difference in breast cancer-specific survival regardless of the treatment and in some subgroups the absolute benefit from radiation therapy is extremely small, it seems reasonable to attempt to develop a system to select patients with DCIS who could be safely treated in the least aggressive way. The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) uses five independent predictors of local recurrence to do exactly that. The combination of tumor size, margin width, nuclear grade, age, and the presence or absence of comedonecrosis can be used to identify subgroups of patients with an extremely low probability of developing a local recurrence after excision alone. When accurate measurements of tumor size cannot be made, margin width can be used as a surrogate parameter for the USC/VNPI. New oncoplastic techniques that allow more extensive excisions

  3. How different terminology for ductal carcinoma in situ impacts women's concern and treatment preferences: a randomised comparison within a national community survey

    PubMed Central

    McCaffery, Kirsten; Nickel, Brooke; Moynihan, Ray; Hersch, Jolyn; Teixeira-Pinto, Armando; Irwig, Les; Barratt, Alexandra

    2015-01-01

    Objective There have been calls to remove ‘carcinoma’ from terminology for in situ cancers such as ductal carcinoma in situ (DCIS), to reduce overdiagnosis and overtreatment. We investigated the effect of describing DCIS as ‘abnormal cells’ versus ‘pre-invasive breast cancer cells’ on women's concern and treatment preferences. Setting and participants Community sample of Australian women (n=269) who spoke English as their main language at home. Design Randomised comparison within a community survey. Women considered a hypothetical scenario involving a diagnosis of DCIS described as either ‘abnormal cells’ (arm A) or ‘pre-invasive breast cancer cells’ (arm B). Within each arm, the initial description was followed by the alternative term and outcomes reassessed. Results Women in both arms indicated high concern, but still indicated strong initial preferences for watchful waiting (64%). There were no differences in initial concern or preferences by trial arm. However, more women in arm A (‘abnormal cells’ first term) indicated they would feel more concerned if given the alternative term (‘pre-invasive breast cancer cells’) compared to women in arm B who received the terms in the opposite order (67% arm A vs 52% arm B would feel more concerned, p=0.001). More women in arm A also changed their preference towards treatment when the terminology was switched from ‘abnormal cells’ to ‘pre-invasive breast cancer cells’ compared to arm B. In arm A, 18% of women changed their preference to treatment while only 6% changed to watchful waiting (p=0.008). In contrast, there were no significant changes in treatment preference in arm B when the terminology was switched (9% vs 8% changed their stated preference). Conclusions In a hypothetical scenario, interest in watchful waiting for DCIS was high, and changing terminology impacted women's concern and treatment preferences. Removal of the cancer term from DCIS may assist in efforts towards

  4. Eliminating "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) terminology in clinical breast practice: The cognitive psychology point of view.

    PubMed

    Pravettoni, Gabriella; Yoder, Whitney R; Riva, Silvia; Mazzocco, Ketti; Arnaboldi, Paola; Galimberti, Viviana

    2016-02-01

    There is evidence from the literature that the terms "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) should be eliminated in clinical breast cancer practice and replaced with the new "ductal intraepithelial neoplasia" (DIN) and "lobular intraepithelial neoplasia" (LIN) terminology. The main purpose of the present article is to expand on this argument from a cognitive psychology perspective and offer suggestions for further research, emphasizing how the elimination of the term "carcinoma" in "in situ" breast cancer diagnoses has the potential to reduce both patient and health care professional confusion and misperceptions that are often associated with the DCIS and LCIS diagnoses, as well as limit the adverse psychological effects of women receiving a DCIS or LCIS diagnosis. We comment on the recent peer-reviewed literature on the clinical implications and psychological consequences for breast cancer patients receiving a DCIS or LCIS diagnosis and we use a cognitive perspective to offer new insight into the benefits of embracing the new DIN and LIN terminology. Using cognitive psychology and cognitive science in general, as a foundation, further research is advocated in order to yield data in support of changing the terminology and therefore, offer a chance to significantly improve the lives and psychological sequelae of women facing such a diagnosis. Typology: Controversies/Short Commentary.

  5. Immunohistochemical detection of antiapoptotic protein X-linked inhibitor of apoptosis in mammary carcinoma.

    PubMed

    Jaffer, Shabnam; Orta, Lurmag; Sunkara, Srinivas; Sabo, Edmond; Burstein, David E

    2007-06-01

    An immunohistochemical survey of X-linked inhibitor of apoptosis (XIAP) expression in mammary carcinoma was performed. XIAP, the most potent of the inhibitor of apoptosis family of caspase inhibitors, has been linked to tumor aggressiveness and therapeutic resistance in several malignancies and is considered an attractive target for cancer drug discovery. Routinely processed sections from 94 ductal carcinomas, 9 lobular carcinomas, and 10 ductal carcinomas with lobular components or features were subjected to citrate-based antigen retrieval, immunostained with anti-XIAP (BD Biosciences, Franklin Lakes, NJ), Envision+ reagents (Dako, Carpinteria, CA), and diaminobenzidine. Positive staining was found in 22.7% of grade 1, 44% of grade 2, and 89.5% of grade 3 ductal carcinomas. Strong staining occurred in no cases of grade 1, 13% of grade 2, and 55.2% of grade 3 ductal carcinomas. XIAP staining increased overall with grade of ductal carcinoma in situ as well. The staining intensity of invasive carcinoma correlated with that of the corresponding ductal carcinoma in situ in 70% of cases. Ductal carcinomas overall showed more staining than lobular carcinomas. XIAP is most strongly and commonly detected in grade 3 ductal carcinoma. The degree of XIAP expression appears frequently to be determined in the preinvasive intraductal phase of tumorigenesis. These findings suggest a possible role of XIAP in the more aggressive clinical behavior of grade 3, compared with lower-grade ductal carcinomas.

  6. Statistical Learning Algorithm for In-situ and Invasive Breast Carcinoma Segmentation

    PubMed Central

    Jayender, Jagadeesan; Gombos, Eva; Chikarmane, Sona; Dabydeen, Donnette; Jolesz, Ferenc A.; Vosburgh, Kirby G.

    2013-01-01

    DCE-MRI has proven to be a highly sensitive imaging modality in diagnosing breast cancers. However, analyzing the DCE-MRI is time-consuming and prone to errors due to the large volume of data. Mathematical models to quantify contrast perfusion, such as the Black Box methods and Pharmacokinetic analysis, are inaccurate, sensitive to noise and depend on a large number of external factors such as imaging parameters, patient physiology, arterial input function, fitting algorithms etc., leading to inaccurate diagnosis. In this paper, we have developed a novel Statistical Learning Algorithm for Tumor Segmentation (SLATS) based on Hidden Markov Models to auto-segment regions of angiogenesis, corresponding to tumor. The SLATS algorithm has been trained to identify voxels belonging to the tumor class using the time-intensity curve, first and second derivatives of the intensity curves (“velocity” and “acceleration” respectively) and a composite vector consisting of a concatenation of the intensity, velocity and acceleration vectors. The results of SLATS trained for the four vectors has been shown for 22 Invasive Ductal Carcinoma (IDC) and 19 Ductal Carcinoma In Situ (DCIS) cases. The SLATS trained for the velocity tuple shows the best performance in delineating the tumors when compared with the segmentation performed by an expert radiologist and the output of a commercially available software, CADstream. PMID:23693000

  7. Hypoxia induces oncogene yes-associated protein 1 nuclear translocation to promote pancreatic ductal adenocarcinoma invasion via epithelial-mesenchymal transition.

    PubMed

    Wei, Honglong; Xu, Zongzhen; Liu, Feng; Wang, Fuhai; Wang, Xin; Sun, Xueying; Li, Jie

    2017-05-01

    Pancreatic ductal adenocarcinoma is one of the most lethal cancers. The Hippo pathway is involved in tumorigenesis and remodeling of tumor microenvironments. Hypoxia exists in the microenvironment of solid tumors, including pancreatic ductal adenocarcinoma and plays a vital role in tumor progression and metastasis. However, it remains unclear how hypoxia interacts with the Hippo pathway to regulate these events. In this study, expressions of yes-associated protein 1 and hypoxia-inducible factor-1α were found to be elevated in pancreatic ductal adenocarcinoma samples compared with those in matched adjacent non-tumor samples. Moreover, hypoxia-inducible factor-1α expression was positively correlated with yes-associated protein 1 level in pancreatic ductal adenocarcinoma tissues. The higher expression of nuclear yes-associated protein 1 was associated with poor histological grade and prognosis for pancreatic ductal adenocarcinoma patients. In vitro, yes-associated protein 1 was highly expressed in pancreatic ductal adenocarcinoma cells. Depletion of yes-associated protein 1 inhibited the invasion of pancreatic ductal adenocarcinoma cells via downregulation of Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-13, and upregulation of E-cadherin. In addition, hypoxia promoted the invasion of pancreatic ductal adenocarcinoma cells via regulating the targeted genes. Hypoxia also deactivated the Hippo pathway and induced yes-associated protein 1 nuclear translocation. Furthermore, depletion of yes-associated protein 1 or hypoxia-inducible factor-1α suppressed the invasion of pancreatic ductal adenocarcinoma cells under hypoxia. Mechanism studies showed that nuclear yes-associated protein 1 interacted with hypoxia-inducible factor-1α and activated Snail transcription to participate in epithelial-mesenchymal transition-mediated and matrix metalloproteinase-mediated remodeling of tumor microenvironments. Collectively, yes-associated protein 1 is an

  8. Validation of transgenic models of breast cancer: ductal carcinoma in situ (DCIS) and Brca1-mutation-related breast cancer.

    PubMed

    Frech, M S; Jones, L P; Furth, P A

    2005-08-01

    Available mouse models of ductal carcinoma in situ (DCIS) and BRCA1-mutation-related breast cancer are reviewed. The best validated mouse models of human DCIS are the conditional estrogen receptor α in mammary tissue (CERM) model initiated by deregulated estrogen receptor α and the serial explant mouse model initiated by p53 deficiency. At present the most useful and best validated mouse model of BRCA1-mutation-related breast cancer uses the cre-lox system to make a conditional Brca1 deletion targeted to mammary epithelial cells. The major shortcoming of the non-conditional Brca1 models is the high incidence of non-mammary tumor development. The use of mammary gland transplants or explants from these mice into nude hosts is one approach that could be used to circumvent this deficiency. Development and validation of a Brca1-mutation-related mouse model of basal cell breast cancer is an important next step.

  9. Protein alterations in infiltrating ductal carcinomas of the breast as detected by nonequilibrium pH gradient electrophoresis and mass spectrometry.

    PubMed

    Kabbage, Maria; Chahed, Karim; Hamrita, Bechr; Guillier, Christelle Lemaitre; Trimeche, Mounir; Remadi, Sami; Hoebeke, Johan; Chouchane, Lotfi

    2008-01-01

    Improvement of breast-cancer detection through the identification of potential cancer biomarkers is considered as a promising strategy for effective assessment of the disease. The current study has used nonequilibrium pH gradient electrophoresis with subsequent analysis by mass spectrometry to identify protein alterations in invasive ductal carcinomas of the breast from Tunisian women. We have identified multiple protein alterations in tumor tissues that were picked, processed, and unambiguously assigned identities by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). The proteins identified span a wide range of functions and are believed to have potential clinical applications as cancer biomarkers. They include glycolytic enzymes, molecular chaperones, cytoskeletal-related proteins, antioxydant enzymes, and immunologic related proteins. Among these proteins, enolase 1, phosphoglycerate kinase 1, deoxyhemoglobin, Mn-superoxyde dismutase, alpha-B-crystallin, HSP27, Raf kinase inhibitor protein, heterogeneous nuclear ribonucleoprotein A2/B1, cofilin 1, and peptidylprolyl isomerase A were overexpressed in tumors compared with normal tissues. In contrast, the IGHG1 protein, the complement C3 component C3c, which are two newly identified protein markers, were downregulated in IDCA tissues.

  10. Protein Alterations in Infiltrating Ductal Carcinomas of the Breast as Detected by Nonequilibrium pH Gradient Electrophoresis and Mass Spectrometry

    PubMed Central

    Kabbage, Maria; Chahed, Karim; Hamrita, Bechr; Guillier, Christelle Lemaitre; Trimeche, Mounir; Remadi, Sami; Hoebeke, Johan; Chouchane, Lotfi

    2008-01-01

    Improvement of breast-cancer detection through the identification of potential cancer biomarkers is considered as a promising strategy for effective assessment of the disease. The current study has used nonequilibrium pH gradient electrophoresis with subsequent analysis by mass spectrometry to identify protein alterations in invasive ductal carcinomas of the breast from Tunisian women. We have identified multiple protein alterations in tumor tissues that were picked, processed, and unambiguously assigned identities by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). The proteins identified span a wide range of functions and are believed to have potential clinical applications as cancer biomarkers. They include glycolytic enzymes, molecular chaperones, cytoskeletal-related proteins, antioxydant enzymes, and immunologic related proteins. Among these proteins, enolase 1, phosphoglycerate kinase 1, deoxyhemoglobin, Mn-superoxyde dismutase, α-B-crystallin, HSP27, Raf kinase inhibitor protein, heterogeneous nuclear ribonucleoprotein A2/B1, cofilin 1, and peptidylprolyl isomerase A were overexpressed in tumors compared with normal tissues. In contrast, the IGHG1 protein, the complement C3 component C3c, which are two newly identified protein markers, were downregulated in IDCA tissues. PMID:18401453

  11. Predictive values of BI-RADS(®) magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS).

    PubMed

    Badan, Gustavo Machado; Piato, Sebastião; Roveda, Décio; de Faria Castro Fleury, Eduardo

    2016-10-01

    The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI. Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy. Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%. BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Challenges in ductal carcinoma in situ risk communication and decision-making: report from an American Cancer Society and National Cancer Institute workshop.

    PubMed

    Partridge, Ann H; Elmore, Joann G; Saslow, Debbie; McCaskill-Stevens, Worta; Schnitt, Stuart J

    2012-01-01

    In September 2010, the American Cancer Society and National Cancer Institute convened a conference to review current issues in ductal carcinoma in situ (DCIS) risk communication and decision-making and to identify directions for future research. Specific topics included patient and health care provider knowledge and attitudes about DCIS and its treatment, how to explain DCIS to patients given the heterogeneity of the disease, consideration of nomenclature changes, and the usefulness of decision tools/aids. This report describes the proceedings of the workshop in the context of the current literature and discusses future directions. Evidence suggests that there is a lack of clarity about the implications and risks of a diagnosis of DCIS among patients, providers, and researchers. Research is needed to understand better the biology and mechanisms of the progression of DCIS to invasive breast cancer and the factors that predict those subtypes of DCIS that do not progress, as well as efforts to improve the communication and informed decision-making surrounding DCIS.

  13. Evaluation of CD56 and CD57 immunostainings for discrimination between endocrine ductal carcinoma in situ and intraductal papilloma.

    PubMed

    Tajima, Shinya; Maeda, Ichiro; Kanemaki, Yoshihide; Nakajima, Yasuo; Tatsunami, Shinobu; Fukuda, Mamoru; Takagi, Masayuki

    2010-06-01

    Endocrine ductal carcinoma in situ (E-DCIS) is an intraductal carcinoma characterized by endocrine features and expression of neuroendocrine markers. E-DCIS and intraductal papilloma (IDP) resemble in their clinical features. However, the former is an intraductal carcinoma, and the latter is an intraductal benign lesion. It is sometimes difficult to distinguish E-DCIS from IDP because both can show near solid intraductal cellular proliferation. Discrimination between lesions is important not only histopathologically, but also clinically. This study aimed to evaluate the applicability of CD56 and CD57 for the discrimination between E-DCIS and IDP. Specimens were obtained from 17 E-DCIS patients as the subject group, and 27 IDP patients as the control group, diagnosed in St Marianna University Hospital. E-DCIS was diagnosed using Chromogranin A, Synaptophysin, and Grimelius stainings by the premise of histopathological features. These specimens were subjected to CD56, CD57 immunostainings. Staining results were compared between E-DCIS and IDP. In our study, CD56 revealed significant differences for distinguishing E-DCIS from IDP as determined by Fisher's test (cutoff: not less than 33-67%< immunopositivity, P < 0.05). We found that not only E-DCIS but also IDP revealed immunopositivity for CD56. However, it is considered that E-DCIS diagnosis is possible by diffuse immunopositivity of CD56 after having been based on histopathology.

  14. Loss of MMP-8 in ductal carcinoma in situ (DCIS)-associated myoepithelial cells contributes to tumour promotion through altered adhesive and proteolytic function.

    PubMed

    Sarper, Muge; Allen, Michael D; Gomm, Jenny; Haywood, Linda; Decock, Julie; Thirkettle, Sally; Ustaoglu, Ahsen; Sarker, Shah-Jalal; Marshall, John; Edwards, Dylan R; Jones, J Louise

    2017-03-23

    Normal myoepithelial cells (MECs) play an important tumour-suppressor role in the breast but display an altered phenotype in ductal carcinoma in situ (DCIS), gaining tumour-promoter functions. Matrix metalloproteinase-8 (MMP-8) is expressed by normal MECs but is lost in DCIS. This study investigated the function of MMP-8 in MECs and the impact of its loss in DCIS. Primary normal and DCIS-associated MECs, and normal (N-1089) and DCIS-modified myoepithelial (β6-1089) cell lines, were used to assess MMP-8 expression and function. β6-1089 lacking MMP-8 were transfected with MMP-8 WT and catalytically inactive MMP-8 EA, and MMP-8 in N-1089 MEC was knocked down with siRNA. The effect on adhesion and migration to extracellular matrix (ECM), localisation of α6β4 integrin to hemidesmosomes (HD), TGF-β signalling and gelatinase activity was measured. The effect of altering MEC MMP-8 expression on tumour cell invasion was investigated in 2D and 3D organotypic models. Assessment of primary cells and MEC lines confirmed expression of MMP-8 in normal MEC and its loss in DCIS-MEC. Over-expression of MMP-8 WT but not MMP-8 EA in β6-1089 cells increased adhesion to ECM proteins and reduced migration. Conversely, knock-down of MMP-8 in N-1089 reduced adhesion and increased migration. Expression of MMP-8 WT in β6-1089 led to greater localisation of α6β4 to HD and reduced retraction fibre formation, this being reversed by MMP-8 knock-down in N-1089. Over-expression of MMP-8 WT reduced TGF-β signalling and gelatinolytic activity. MMP-8 knock-down enhanced TGF-β signalling and gelatinolytic activity, which was reversed by blocking MMP-9 by knock-down or an inhibitor. MMP-8 WT but not MMP-8 EA over-expression in β6-1089 reduced breast cancer cell invasion in 2D and 3D invasion assays, while MMP-8 knock-down in N-1089 enhanced cancer cell invasion. Staining of breast cancer cases for MMP-8 revealed a statistically significant loss of MMP-8 expression in DCIS with invasion

  15. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    PubMed Central

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis. PMID:27757356

  16. Matricellular protein CCN1 (CYR61) expression is associated with high-grade ductal carcinoma in situ.

    PubMed

    Saglam, Ozlen; Dai, Feng; Husain, Seema; Zhan, Yilei; Toruner, Gokce; Haines, G Kenneth

    2014-06-01

    Cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma overexpressed gene (CCN) comprise a family of matricellular proteins that have multiple physiologic functions including development, tissue repair, cell adhesion, migration, and proliferation. The expression of CCN1, cyclin D1, β-catenin, and p53 was explored by immunohistochemistry in different grades of ductal carcinoma in situ (DCIS) cases. These cases did not contain any infiltrating carcinoma components. In addition, all cysteine-rich protein 61 gene exons (encoding the CCN1 protein) were sequenced in 30 samples. Allred and H-scores were calculated for expression in both DCIS and the surrounding benign breast tissue. All cases of DCIS showed degrees of cytoplasmic CCN1 staining with median H-scores of 170, 160, and 60 in grades 3, 2, and 1, respectively (P = .043). Twelve of 28 DCIS 3, 1 of 15 DCIS 2, and 0 of 18 DCIS 1 also showed nuclear staining for CCN1. The cytoplasmic staining difference was preserved when the cases were divided into estrogen receptor (ER)+/DCIS grade 1, ER+/DCIS 2 and 3, and ER-/DCIS 2 and 3 by the H-score (P = .037). Cyclin D1 expression was positively correlated with the CCN1 cytoplasmic H-score in all DCIS samples (P = .038). Membranous β-catenin expression correlated with the grade of intraepithelial carcinoma by both H-score (P = .047) and Allred score (P = .026). Our results suggest that CCN1 has a role in the development of intraepithelial carcinoma. CCN1 expression correlates with grade of DCIS independent of ER status. It can induce cell cycle progression through cyclin D1. It is warranted to study high expression of CCN1 in DCIS as an independent risk factor in a larger cohort.

  17. Loss of Heterozygosity on Chromosome 11p15 during Histological Progression in Microdissected Ductal Carcinoma of the Breast

    PubMed Central

    Lichy, Jack H.; Zavar, Maryam; Tsai, Mark M.; O’Leary, Timothy J.; Taubenberger, Jeffery K.

    1998-01-01

    Microdissection of histologically identifiable components from formalin-fixed, paraffin-embedded tissue sections allows molecular genetic analyses to be correlated directly with pathological findings. In this study, we have characterized loss of heterozygosity (LOH) at chromosome 11p15 at different stages of progression in microdissected tumor components from 115 ductal carcinomas of the breast. Microdissected foci of intraductal, infiltrating, and metastatic tumors were analyzed to determine the stage of progression at which LOH at 11p15 occurs. LOH was detected in 43 (37%) of 115 cases. Foci of intraductal carcinoma could be microdissected from 85 cases, of which 30 (35%) showed LOH at some stage of progression. LOH was detected in the intraductal component in 26 of these 30 cases. Interstitial deletions were characterized by using a panel of 10 highly polymorphic markers. The smallest region of overlap (SRO) for LOH at 11p15 was bounded by the markers D11S4046 and D11S1758. LOH at 11p15.5 showed no correlation with estrogen receptor status, the presence of positive lymph nodes, tumor size, histological grade, or long-term survival. We conclude that 11p15 LOH usually occurs early in breast cancer development but less frequently does not develop until the infiltrating or metastatic stages of tumor progression. PMID:9665488

  18. Accuracy of classification of invasive lobular carcinoma on needle core biopsy of the breast.

    PubMed

    Naidoo, Kalnisha; Beardsley, Brooke; Carder, Pauline J; Deb, Rahul; Fish, David; Girling, Anne; Hales, Sally; Howe, Miles; Wastall, Laura M; Lane, Sally; Lee, Andrew H S; Philippidou, Marianna; Quinn, Cecily; Stephenson, Tim; Pinder, Sarah E

    2016-12-01

    Although the UK National Institute for Health and Care Excellence guidelines recommend that in patients with biopsy-proven invasive lobular carcinoma (ILC), preoperative MRI scan is considered, the accuracy of diagnosis of ILC in core biopsy of the breast has not been previously investigated. Eleven pathology laboratories from the UK and Ireland submitted data on 1112 cases interpreted as showing features of ILC, or mixed ILC and IDC/no special type (NST)/other tumour type, on needle core biopsy through retrieval of histology reports. Of the total 1112 cases, 844 were shown to be pure ILC on surgical excision, 154 were mixed ILC plus another type (invariably ductal/NST) and 113 were shown to be ductal/NST. Of those lesions categorised as pure ILC on core, 93% had an element of ILC correctly identified in the core biopsy sample and could be considered concordant. Of cores diagnosed as mixed ILC plus another type on core, complete agreement between core and excision was 46%, with 27% cases of pure ILC, whilst 26% non-concordant. These data indicate that there is not a large excess of expensive MRIs being performed as a result of miscategorisation histologically. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate.

    PubMed

    Zumwalde, Nicholas A; Haag, Jill D; Sharma, Deepak; Mirrielees, Jennifer A; Wilke, Lee G; Gould, Michael N; Gumperz, Jenny E

    2016-04-01

    Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of preinvasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Because most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyte compartment of non-cancerous human breast tissue and identified a subset of T lymphocytes that can be pharmacologically targeted to enhance their responses to breast cancer cells. Specifically, Vδ2(+) γδ T cells were consistently present in preparations of mammary ductal epithelial organoids and they proliferated in response to zoledronic acid, an aminobisphosphonate drug. Vδ2(+) T cells from breast ductal organoids produced the antitumor cytokine IFNγ and efficiently killed bisphosphonate-pulsed breast carcinoma cells. These findings demonstrate the potential for exploiting the ability of Vδ2(+) γδ T cells to respond to FDA-approved bisphosphonate drugs as a novel immunotherapeutic approach to inhibit the outgrowth of breast cancers.

  20. Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

    PubMed

    Magers, Martin J; Dueber, Julie C; Lew, Madelyn; Pang, Judy C; Davenport, Robertson D

    2016-06-01

    Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Diagnostic and therapeutic implications of a novel immunohistochemical panel detecting duodenal mucosal invasion by pancreatic ductal adenocarcinoma

    PubMed Central

    Sopha, Sabrina C; Gopal, Purva; Merchant, Nipun B; Revetta, Frank L; Gold, David V; Washington, Kay; Shi, Chanjuan

    2013-01-01

    Background: We investigated a series of pancreaticoduodenectomy and duodenal biopsies with a panel of immunohistochemical markers to identify duodenal mucosal invasion by pancreatic ductal adenocarcinoma (PDAC), including markers of poor prognosis and targets of promising novel immunotherapies. Materials and Methods: Eighteen consecutive pancreaticoduodenectomy specimens with duodenal mucosal invasion by PDAC were examined for expression of MUC1, MUC4, MUC5AC, MUC6, mesothelin, MUC2, CDX2, and DPC4 on formalin-fixed, paraffin-embedded sections of duodenal-ampullary-pancreatic junctions. Expression of all but MUC6 was also assessed in duodenal biopsies from 12 patients with duodenal mucosal invasion by PDAC. Results: The duodenal mucosa expressed MUC1 (crypts), MUC2 (goblet cells), MUC6 (Brunner glands), CDX2, and DPC4. PDACs in the duodenal mucosa from the resection (n=16-18) and biopsy (n=12) specimens were marked as follows: MUC1 100% (30/30), MUC4 83% (24/29), MUC5AC 83% (25/30), mesothelin 82% (23/28), MUC2 7% (2/30), and CDX2 36% (10/28). Loss of DPC4 expression was seen in 16 of 29 (55%) cases. Reactive mucosa adjacent to PDAC expressed MUC4, MUC5AC and mesothelin in 65% (17/26), 19% (5/27), and 19% (5/26) of cases, respectively. While MUC5AC and mesothelin had high diagnostic accuracy for detection of PDAC, MUC2, CDX2 and DPC4 expression demonstrated negative correlation with PDAC, with absent expression being highly specific for PDAC. Conclusion: Immunohistochemical labeling for PDAC biomarkers may aid the diagnosis of PDAC in duodenal biopsy, especially in situations where diagnosis of a pancreatic mass is challenging. PMID:24228110

  2. Bile duct carcinoma involving the common channel associated with pancreaticobiliary maljunction shows an extension pattern similar to ductal carcinoma of the pancreas.

    PubMed

    Yoshida, Nao; Esaki, Minoru; Kishi, Yoji; Shimada, Kazuaki; Ojima, Hidenori; Kanai, Yae; Hiraoka, Nobuyoshi

    2013-08-01

    Biliary tract cancer occurs frequently in patients with pancreaticobiliary maljunction (PBM), although no details of its clinicopathological characteristics have been reported. Here we describe a case of bile duct (BD) cancer that developed in association with PBM. This BD cancer involved the common channel, extended to the main pancreatic duct (MPD) via the common channel, and invaded the pancreatic parenchyma, where its growth and spread, and features of its recurrence, were similar to those of ductal carcinoma of the pancreas. We assumed that MPD extension of BD cancer via the common channel was the reason for its deep spread to the pancreas, since BD cancer usually spreads along the BD and rarely reaches the common channel of the ampulla of Vater. During the follow-up of patients with PBM, attention should be paid to involvement of the common channel by BD cancer and also to cancer developing silently in the pancreas after extrahepatic BD resection.

  3. Prognostic implication of the tumor location according to molecular subtypes in axillary lymph node-positive invasive ductal cancer in a Korean population.

    PubMed

    Lim, Seung Taek; Choi, Jung Eun; Kim, Sei Joong; Kim, Hyun Ah; Kim, Ji Young; Park, Heung Kyu; Suh, Young Jin

    2016-04-01

    Previous studies have not considered the axillary lymph node status when investigating the prognostic role of tumor location according to each molecular subtype. The present study aimed to investigate the prognostic implication of tumor location according to each molecular subtype in Korean invasive ductal carcinoma (IDC) patients with axillary lymph node metastasis. Data from 7856 Korean IDC women with axillary lymph node metastasis were retrospectively analyzed. According to tumor location, patients were divided into the following groups: upper-outer quadrant, lower-outer quadrant, upper-inner quadrant, lower-inner quadrant (LIQ), and central group. Overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated according to tumor location and molecular subtype. A subgroup analysis based on tumor size categorization was also performed. The patients' mean age was 47.97 ± 9.64 years, and the median follow-up time was 90 months. The LIQ group showed significantly worse prognosis in OS and BCSS (76.4 and 83.3 %, respectively) compared with the other groups, which was only significant in human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative (TN) subtypes. In the subgroup analysis according to tumor size, the LIQ group showed a significantly worse prognosis in OS and BCSS compared with the other groups, in HER2 and TN subtypes, and only in patients with more than T2 stage. In Korean IDC patients with axillary lymph node metastasis, LIQ tumor location was associated with poor prognosis among those with HER2 and TN molecular subtypes and especially in those with more than T2 stage.

  4. Immunohistochemical comparison of MUC1, CA125, and Her2Neu in invasive micropapillary carcinoma of the urinary tract and typical invasive urothelial carcinoma with retraction artifact.

    PubMed

    Sangoi, Ankur R; Higgins, John P; Rouse, Robert V; Schneider, Anne G; McKenney, Jesse K

    2009-05-01

    On the basis of recent clinical studies, some urologic oncologists do not offer bladder-sparing therapy for patients diagnosed with micropapillary carcinoma of the urinary bladder, even in the setting superficially invasive disease. Unfortunately, the distinction of invasive micropapillary carcinoma from typical invasive urothelial carcinoma with prominent retraction artifact may be difficult in some cases. In this study, we compared the immunophenotype of invasive micropapillary carcinoma to invasive urothelial carcinoma with retraction artifact using antibodies previously reported as specific for micropapillary carcinoma. Immunohistochemical staining was performed on 24 invasive micropapillary carcinomas of the urinary tract and 24 case controls of invasive urothelial carcinoma with retraction artifact using monoclonal antibodies MUC1, CA125, and Her2Neu. The staining extent and intensity for MUC1 and CA125 were scored on one representative section per case. Immunostaining for Her2Neu was scored based on the 2007 CAP/ASCO guidelines for breast carcinoma. Basal ('reverse-apical') MUC1 staining was identified in 23 of the 24 (96%) invasive micropapillary carcinomas and in 15 of the 24 (63%) invasive urothelial carcinomas with retraction artifact (P=0.0102). Membranous reactivity with CA125 was seen in 8 of the 24 (33%) invasive micropapillary carcinomas and in 3 of the 24 (13%) invasive urothelial carcinomas with retraction artifact (P=0.1681). Positive (3+) membranous Her2Neu staining was present in 6 of 24 (25%) invasive micropapillary carcinomas and in 2 of the 24 (8%) invasive urothelial carcinomas with retraction artifact (P=0.2448). The specificity for invasive micropapillary carcinoma vs invasive urothelial carcinoma with retraction artifact using antibodies MUC1, CA125, and Her2Neu was 37, 87, and 92%, respectively. Invasive micropapillary carcinoma more commonly showed immunoreactivity for MUC1, CA125, and Her2Neu compared to invasive urothelial carcinoma

  5. Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient.

    PubMed

    Pfrommer, Sarah; Weber, Achim; Dutkowski, Philipp; Schäfer, Niklaus G; Müllhaupt, Beat; Bourquin, Jean-Pierre; Breitenstein, Stefan; Pestalozzi, Bernhard C; Stenner, Frank; Renner, Christoph; D'Addario, Giannicola; Graf, Hans-Jörg; Knuth, Alexander; Clavien, Pierre-Alain; Samaras, Panagiotis

    2013-01-01

    Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life.

  6. Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient

    PubMed Central

    Pfrommer, Sarah; Weber, Achim; Dutkowski, Philipp; Schäfer, Niklaus G.; Müllhaupt, Beat; Bourquin, Jean-Pierre; Breitenstein, Stefan; Pestalozzi, Bernhard C.; Stenner, Frank; Renner, Christoph; D'Addario, Giannicola; Graf, Hans-Jörg; Knuth, Alexander; Clavien, Pierre-Alain; Samaras, Panagiotis

    2013-01-01

    Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life. PMID:24163668

  7. Molecular and immunochemical analyses of RB1 and cyclin D1 in human ductal pancreatic carcinomas and cell lines.

    PubMed

    Huang, L; Lang, D; Geradts, J; Obara, T; Klein-Szanto, A J; Lynch, H T; Ruggeri, B A

    1996-02-01

    Somatic mutations in the retinoblastoma-1 gene (RB1) and loss of RB1 protein function have been implicated in a number of human malignancies, but the role of RB1 gene and protein abnormalities in ductal pancreatic cancer (DPCA) is virtually unknown. We therefore analyzed expression of the RB1 protein immunohistochemically and/or by western blotting in a total of 54 sporadic and eight familial cases of archival and frozen DPCA and in 18 pancreatic carcinoma cell lines by using the antibodies RB-WL-1, 84-B3-1, and PMG3-245. Mutations in the RB1 promotor region and exons 13-21 of the RB1 gene were likewise examined by single-strand conformation polymorphism (SSCP) analyses and DNA sequencing of genomic DNA from 30 microdissected primary pancreatic tumors and the pancreatic carcinoma cell lines. Moreover, amplification and expression of a major regulatory component of RB1 function, cyclin D1, were assessed by southern and immunohistochemical analyses, respectively. The DPCAs were heterogeneous in both the intensity of RB1 nuclear staining and the percentage of immunoreactive cells. The tumors often had areas where RB1 staining was weak or absent adjacent to normal pancreatic tissue; however, only two of 32 archival cases and one of 30 frozen cases of DPCA completely lacked RB1 nuclear staining. Immunohistochemical and western blot analyses of 18 pancreatic carcinoma cell lines demonstrated the absence of RB1 expression in only two cell lines, Capan-1 and QGP-1. Analyses of the RB1 gene and promotor region by SSCP and DNA sequencing largely confirmed the immunochemical findings. Three of 30 primary carcinomas had abnormalities revealed by SSCP analyses. In one case a single base-pair deletion was confirmed in exon 18 and resulted in premature termination and the absence of detectable RB1 protein. A second case had TAC-->TTC missense mutation in exon 13. The third primary carcinoma could not be reliably sequenced because it had a low percentage of epithelial cells. The

  8. The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.

    PubMed

    Jean-Louis, Christopher J; Masdon, Joshua; Smith, Betsy; Battles, Oscar; Dale, Paul

    2017-05-01

    For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS

  9. Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Invasive Lobular Carcinoma

    SciTech Connect

    Shah, Chirag; Wilkinson, J. Ben; Shaitelman, Simona; Grills, Inga; Wallace, Michelle; Mitchell, Christina; Vicini, Frank

    2011-11-15

    Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

  10. Eight-year update of a prospective study of wide excision alone for small low- or intermediate-grade ductal carcinoma in situ (DCIS).

    PubMed

    Wong, Julia S; Chen, Yu-Hui; Gadd, Michele A; Gelman, Rebecca; Lester, Susan C; Schnitt, Stuart J; Sgroi, Dennis C; Silver, Barbara J; Smith, Barbara L; Troyan, Susan L; Harris, Jay R

    2014-01-01

    Whether wide excision with margins ≥1 cm is sufficient treatment for small low- or intermediate-grade ductal carcinoma in situ (DCIS) is unclear. This is an updated analysis of a phase II, single-arm, prospective trial testing this hypothesis. A total of 158 patients with low- or intermediate-grade DCIS who underwent wide excision alone (without radiation or tamoxifen) were entered onto the trial from 1995 to 2002. Entry criteria included mammographic extent ≤2.5 cm, predominantly low or intermediate nuclear grade, and excision with final microscopic margins ≥1 cm. Eight-year minimum potential follow-up was required for inclusion in the analysis; the final population comprised 143 patients. Cumulative incidence curves were generated to assess rates of local recurrence (LR) or other events. Median follow-up time was 11 years. Nineteen patients (13 %) had LR as a first event within 8 years. Thirteen LR (68 %) were DCIS only and six (32 %) were invasive. Fourteen (74 %) occurred in the original quadrant. The 10-year estimated cumulative incidence of LR was 15.6 %. The estimated annual percentage rate of LR was 1.9 % per patient-year. With longer follow-up, there remains a substantial and ongoing risk of LR in patients with favorable DCIS treated with wide excision margins without radiation. This information should be useful as patients and clinicians weigh the options of wide excision with and without radiation.

  11. Family history and risk of ductal carcinoma in situ and triple negative breast cancer in a Han Chinese population: a case-control study.

    PubMed

    Zhou, Wenbin; Pan, Hong; Liang, Mengdi; Xia, Kai; Liang, Xiuqing; Xue, Jinqiu; Cheng, Lin; Xue, Jialei; Chen, Si; Liu, Xiaoan; Ding, Qiang; Ling, Lijun; Wang, Shui

    2013-10-01

    The association between family history and risk of triple negative breast cancer and ductal carcinoma in situ (DCIS) has not been well investigated, especially in Asian populations. We investigated the association between family history and risk of DCIS or triple negative breast cancer in a Han Chinese population. A case-control study, comprising 926 breast cancer patients and 1,187 benign breast disease controls, was conducted in our hospital. Multivariate logistic regression was used to assess the relationships between family history and risk of DCIS or triple negative breast cancer. Subjects with a family history of breast cancer had higher breast cancer risk than those without a family history (odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.26 to 3.52). Family history was not significantly associated with an increased risk of DCIS (OR = 1.27, 95% CI = 0.36 to 4.46), while family history was significantly associated with an increased risk of invasive breast cancer (OR = 2.22, 95% CI = 1.32 to 3.75), irrespective of triple negative breast cancer (OR = 3.35, 95% CI = 1.43 to 7.88) or non-triple negative breast cancer (OR = 2.14, 95% CI = 1.21 to 3.80). Our results indicate that having a family history of breast cancer is associated with an increased risk of triple negative breast cancer with a magnitude of association similar to that for non-triple negative breast cancer. Furthermore, family history is not significantly associated with an increased risk of DCIS. Future cohort studies with larger sample sizes are still needed to explore these relationships.

  12. Widespread chromosomal abnormalities in high-grade ductal carcinoma in situ of the breast. Comparative genomic hybridization study of pure high-grade DCIS.

    PubMed

    Moore, E; Magee, H; Coyne, J; Gorey, T; Dervan, P A

    1999-03-01

    For a variety of technical reasons it is rarely possible to study cytogenetic abnormalities in ductal carcinoma in situ (DCIS) using traditional techniques. However, by combining molecular biology and computerized image analysis it is possible to carry out cytogenetic analyses on formalin-fixed, paraffin-embedded tissue, using comparative genomic hybridization (CGH). The purpose of this study was to identify the prevalence of chromosomal amplifications and deletions in high-grade DCIS and to look specifically for unique or consistent abnormalities in this pre-invasive cancer. Twenty-three cases of asymptomatic, non-palpable, screen-detected, high-grade DCIS were examined using CGH on tumour cells obtained from histology slides. All cases showed chromosomal abnormalities. A wide variety of amplifications and deletions were spread across the genome. The most frequent changes were gains of chromosomes 17 (13 of 23), 16p (13 of 23), and 20q (9 of 23) and amplifications of 11q13 (22 of 23), 12q 24.1-24.2 (12 of 23), 6p21.3 (11 of 23), and 1q31-qter (6 of 23). The most frequent deletions were on 13q 21.3-q33 (7 of 23), 9p21 (4 of 23), and 6q16.1 (4 of 23). These findings indicate that high-grade DCIS is, from a cytogenetic viewpoint, an advanced lesion. There was no absolutely consistent finding in every case, but amplification of 11q13 was found in 22 of the 23 cases. The precise significance of this is unknown at present. This region of chromosome 11q harbours a number of known oncogenes, including cyclin D1 andINT2. It is likely that many of these findings are the result of accumulated chromosomal abnormalities, reflecting an unstable genome in established malignancy.

  13. Patient-calibrated agent-based modelling of ductal carcinoma in situ (DCIS): From microscopic measurements to macroscopic predictions of clinical progression

    PubMed Central

    Macklin, Paul; Edgerton, Mary E.; Thompson, Alastair M.; Cristini, Vittorio

    2012-01-01

    Ductal carcinoma in situ (DCIS)—a significant precursor to invasive breast cancer—is typically diagnosed as microcalcifications in mammograms. However, the effective use of mammograms and other patient data to plan treatment has been restricted by our limited understanding of DCIS growth and calcification. We develop a mechanistic, agent-based cell model and apply it to DCIS. Cell motion is determined by a balance of biomechanical forces. We use potential functions to model interactions with the basement membrane and amongst cells of unequal size and phenotype. Each cell’s phenotype is determined by genomic/proteomic- and microenvironment-dependent stochastic processes. Detailed “sub-models” describe cell volume changes during proliferation and necrosis; we are the first to account for cell calcification. We introduce the first patient-specific calibration method to fully constrain the model based upon clinically-accessible histopathology data. After simulating 45 days of solid-type DCIS with comedonecrosis, the model predicts: necrotic cell lysis acts as a biomechanical stress relief, and is responsible for the linear DCIS growth observed in mammography; the rate of DCIS advance varies with the duct radius; the tumour grows 7 to 10 mm per year—consistent with mammographic data; and the mammographic and (post-operative) pathologic sizes are linearly correlated—in quantitative agreement with the clinical literature. Patient histopathology matches the predicted DCIS microstructure: an outer proliferative rim surrounds a stratified necrotic core with nuclear debris on its outer edge and calcification in the centre. This work illustrates that computational modelling can provide new insight on the biophysical underpinnings of cancer. It may one day be possible to augment a patient’s mammography and other imaging with rigorously-calibrated models that help select optimal surgical margins based upon the patient’s histopathologic data. PMID:22342935

  14. Development of Aggressive Pancreatic Ductal Adenocarcinomas Depends on Granulocyte Colony Stimulating Factor Secretion in Carcinoma Cells.

    PubMed

    Pickup, Michael W; Owens, Philip; Gorska, Agnieszka E; Chytil, Anna; Ye, Fei; Shi, Chanjuan; Weaver, Valerie M; Kalluri, Raghu; Moses, Harold L; Novitskiy, Sergey V

    2017-09-01

    The survival rate for pancreatic ductal adenocarcinoma (PDAC) remains low. More therapeutic options to treat this disease are needed, for the current standard of care is ineffective. Using an animal model of aggressive PDAC (Kras/p48(TGFβRIIKO)), we discovered an effect of TGFβ signaling in regulation of G-CSF secretion in pancreatic epithelium. Elevated concentrations of G-CSF in PDAC promoted differentiation of Ly6G(+) cells from progenitors, stimulated IL10 secretion from myeloid cells, and decreased T-cell proliferation via upregulation of Arg, iNOS, VEGF, IL6, and IL1b from CD11b(+) cells. Deletion of csf3 in PDAC cells or use of a G-CSF-blocking antibody decreased tumor growth. Anti-G-CSF treatment in combination with the DNA synthesis inhibitor gemcitabine reduced tumor size, increased the number of infiltrating T cells, and decreased the number of Ly6G(+) cells more effectively than gemcitabine alone. Human analysis of human datasets from The Cancer Genome Atlas and tissue microarrays correlated with observations from our mouse model experiments, especially in patients with grade 1, stage II disease. We propose that in aggressive PDAC, elevated G-CSF contributes to tumor progression through promoting increases in infiltration of neutrophil-like cells with high immunosuppressive activity. Such a mechanism provides an avenue for a neoadjuvant therapeutic approach for this devastating disease. Cancer Immunol Res; 5(9); 718-29. ©2017 AACR. ©2017 American Association for Cancer Research.

  15. The Efficacy of Intraoperative Frozen Section Analysis During Breast-Conserving Surgery for Patients with Ductal Carcinoma In Situ

    PubMed Central

    Kim, Mi Jin; Kim, Cheol Seung; Park, Young Sam; Choi, Eun Hye; Han, Kyu Dam

    2016-01-01

    INTRODUCTION Recently, the incidence of ductal carcinoma in situ (DCIS), a noninvasive breast malignancy, has increased. This has resulted in an increase in the incidence of breast-conserving surgery (BCS). Numerous studies have suggested that intraoperative frozen section analysis (IFSA) could reduce the rate of additional excisions required to obtain adequate resection margins. However, DCIS is a known risk factor for positive margin status during BCS. Furthermore, some authors have concluded that IFSA may not be reliable for the detection of DCIS. AIM The aim of this study was to evaluate the safety and efficacy of IFSA in patients with DCIS. METHODS The operative and pathological reports of patients with DCIS, who underwent BCS at our institute between 2006 and 2015, were retrospectively reviewed. The results of IFSA and the pathological findings of final reanalyzed frozen tissue specimens were analyzed. RESULTS In total, 25 patients were included in our analysis. None of the patients required additional operations. The correct diagnosis rate for IFSA was 89.6%, with a sensitivity and specificity of 60.0% and 95.8%, respectively. CONCLUSION IFSA could be beneficial for determining safety resection margins in patients with DCIS. PMID:27980416

  16. Clinicopathologic assessment of pancreatic ductal carcinoma located at the head of the pancreas, in relation to embryonic development.

    PubMed

    Okamura, Yukiyasu; Fujii, Tsutomu; Kanzaki, Akiyuki; Yamada, Suguru; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Nakao, Akimasa

    2012-05-01

    Pancreaticoduodenectomy is performed for pancreatic head cancer that originated from the dorsal or ventral primordium. Although the extent of lymph node (LN) dissection is the same irrespective of the origin, the lymphatic continuities may differ between the 2 primordia. Between March 2003 and September 2010, 152 patients underwent pancreaticoduodenectomy for pancreatic cancer. One hundred six patients were assigned into 2 groups according to tumor location on preoperative computed tomography, and their clinical and pathological features were retrospectively analyzed in view of the embryonic development of the pancreas. Sixty of 106 patients were classified with tumors that were derived from the dorsal pancreas (D group) and 46 from the ventral pancreas (V group). The frequency of LN involvement around the middle colic artery (LN 15) in the D group was higher than in the V group (P = 0.008). The rate of additional resection of the pancreas tended to be higher in the D group (P = 0.067). The present study showed the detailed pattern of spread of pancreatic ductal carcinoma to the LNs and provided important information for determining the optimal surgical strategy.

  17. Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment

    PubMed Central

    Takagi, K; Ishida, T; Miki, Y; Hirakawa, H; Kakugawa, Y; Amano, G; Ebata, A; Mori, N; Nakamura, Y; Watanabe, M; Amari, M; Ohuchi, N; Sasano, H; Suzuki, T

    2013-01-01

    Background: Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment. Methods: Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis. Results: Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues. Conclusion: These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens. PMID:23756858

  18. Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment.

    PubMed

    Takagi, K; Ishida, T; Miki, Y; Hirakawa, H; Kakugawa, Y; Amano, G; Ebata, A; Mori, N; Nakamura, Y; Watanabe, M; Amari, M; Ohuchi, N; Sasano, H; Suzuki, T

    2013-07-09

    Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment. Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis. Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues. These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens.

  19. Variation in detection of ductal carcinoma in situ during screening mammography: a survey within the International Cancer Screening Network.

    PubMed

    Lynge, Elsebeth; Ponti, Antonio; James, Ted; Májek, Ondřej; von Euler-Chelpin, My; Anttila, Ahti; Fitzpatrick, Patricia; Frigerio, Alfonso; Kawai, Masaaki; Scharpantgen, Astrid; Broeders, Mireille; Hofvind, Solveig; Vidal, Carmen; Ederra, Maria; Salas, Dolores; Bulliard, Jean-Luc; Tomatis, Mariano; Kerlikowske, Karla; Taplin, Stephen

    2014-01-01

    There is concern about detection of ductal carcinoma in situ (DCIS) in screening mammography. DCIS accounts for a substantial proportion of screen-detected lesions but its effect on breast cancer mortality is debated. The International Cancer Screening Network conducted a comparative analysis to determine variation in DCIS detection. Data were collected during 2004-2008 on number of screening examinations, detected breast cancers, DCIS cases and Globocan 2008 breast cancer incidence rates derived from national or regional cancer registers. We calculated screen-detection rates for breast cancers and DCIS. Data were obtained from 15 screening settings in 12 countries; 7,176,050 screening examinations; 29,605 breast cancers and 5324 DCIS cases. The ratio between highest and lowest breast cancer incidence was 2.88 (95% confidence interval (CI) 2.76-3.00); 2.97 (95% CI 2.51-3.51) for detection of breast cancer; and 3.49 (95% CI 2.70-4.51) for detection of DCIS. Considerable international variation was found in DCIS detection. This variation could not be fully explained by variation in incidence nor in breast cancer detection rates. It suggests the potential for wide discrepancies in management of DCIS resulting in overtreatment of indolent DCIS or undertreatment of potentially curable disease. Comprehensive cancer registration is needed to monitor DCIS detection. Efforts to understand discrepancies and standardise management may improve care. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women.

    PubMed

    Looi, Lai-Meng; Cheah, Phaik-Leng; Ng, Min-Hwei; Yip, Cheng-Har; Mun, Kein-Seong; Rahman, Nazarina Abdul

    2010-01-01

    A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.

  1. Differentiation of ductal carcinoma in situ versus fibrocystic changes by magnetic resonance imaging: are there pathognomonic imaging features?

    PubMed

    Dietzel, Matthias; Kaiser, Clemens G; Wenkel, Evelyn; Clauser, Paola; Uder, Michael; Schulz-Wendtland, Rüdiger; Baltzer, Pascal At

    2017-10-01

    Background In breast magnetic resonance imaging (MRI), the diagnosis of ductal carcinoma in situ (DCIS) remains controversial; the most challenging cause of false-positive DCIS diagnosis is fibrocystic changes (FC). Purpose To search for typical and pathognomonic patterns of DCIS and FC using a standard clinical MRI protocol. Material and Methods Consecutive patients scheduled for breast MRI (standardized protocols @ 1.5T: dynamic-T1-GRE before/after Gd-DTPA [0.1 mmol/kg body weight (BW)]; T1-TSE), with subsequent pathological sampling, were investigated. Sixteen MRI descriptors were prospectively assessed by two experienced radiologists in consensus (blinded to pathology) and explored in patients with DCIS (n = 77) or FC (n = 219). Univariate and multivariate statistics were performed to identify the accuracy of descriptors (alone, combined). Furthermore, pathognomonic descriptor-combinations with an accuracy of 100% were explored (χ(2) statistics; decision trees). Results Six breast MRI descriptors significantly differentiated DCIS from FC ( Pcorrected < 0.05; odds ratio < 7.9). Pathognomonic imaging features were present in 33.8% (n = 100) of all cases allowing the identification of 42.9% of FC (n = 94). Conclusion Pathognomonic patterns of DCIS and FC were frequently observed in a standard clinical MRI protocol. Such imaging patterns could decrease the false-positive rate of breast MRI and hence might help to decrease the number of unnecessary biopsies in this clinically challenging subgroup.

  2. Cutaneous invasion from sarcomatoid urothelial carcinoma: clinical and dermatopathologic features*

    PubMed Central

    Bernardes Filho, Fred; de Melo, Alessandro Severo Alves; Pires, Andréa Rodriguez Cordovil; Lupi, Omar; Neves, Daniel Gama das; da Cruz, Margareth Fernandes; Kac, Bernard Kawa

    2016-01-01

    In Brazil, without considering the non-melanoma skin tumors, bladder cancer in men is the eighth most common, and the urothelial carcinoma or transitional cell carcinoma is the most common among these. Cutaneous metastases from urothelial neoplasms appear as single or multiple erythematous, infiltrated nodules or plaques, and like other cases of distant disease, it is indicative of poor prognosis. The invasive urothelial carcinoma is recognized for its ability to present divergent differentiation and morphological variants. The sarcomatoid urothelial carcinoma is a rare cancer that consists of two different components: one composed of epithelial tissue and the other with sarcomatoid features of mesenchymal origin. The authors describe a case of cutaneous metastasis of sarcomatoid urothelial carcinoma in a 63-year-old male patient. PMID:26982782

  3. Merkel cell polyomavirus infection in both components of a combined Merkel cell carcinoma and basal cell carcinoma with ductal differentiation; each component had a similar but different novel Merkel cell polyomavirus large T antigen truncating mutation.

    PubMed

    Iwasaki, Takeshi; Kodama, Hajime; Matsushita, Michiko; Kuroda, Naoto; Yamasaki, Yoshikazu; Murakami, Ichiro; Yamamoto, Osamu; Hayashi, Kazuhiko

    2013-03-01

    Merkel cell polyomavirus infects up to 80% of patients with Merkel cell carcinoma. Combined Merkel cell carcinoma and cutaneous tumors occur occasionally. Previous reports have suggested that Merkel cell polyomavirus is absent from combined Merkel cell carcinoma and squamous cell carcinomas. This is the first report that Merkel cell polyomavirus infected in both lesions of a combined Merkel cell carcinoma and basal cell carcinoma. A 92-year-old Japanese man presented with a right thigh small subcutaneous mass. Histologic examination revealed a combined tumor with Merkel cell carcinoma and basal cell carcinoma with ductal differentiation. Both tumors and intermingled Merkel cells in basal cell carcinoma expressed Merkel cell polyomavirus large T antigen, and 17 and 240 copies of Merkel cell polyomavirus/cell were detected in the microdissected Merkel cell carcinoma and basal cell carcinoma specimens, respectively. Mutation analysis of Merkel cell polyomavirus large T antigen revealed a novel truncating mutation in Merkel cell carcinoma and a similar but different mutation in the basal cell carcinoma. These results suggest that each was infected by a different Merkel cell polyomavirus subclone derived from a single Merkel cell polyomavirus.

  4. Impact of Obesity on Tamoxifen Chemoprevention in a Model of Ductal Carcinoma In Situ

    DTIC Science & Technology

    2010-10-01

    postmenopausal women, in fact, 30-50% of breast cancer deaths in post- menopausal women may be attributed to excess body weight (1). The HER-2/neu...in carcinoma cells. However, tumors negative for estrogen receptor (ER-) confer a much worse prognosis (3). Energy balance modulation through diet ...model, in which mice were fed a standard diet -induced obesity regimen. Task 1 was to modulate diets in MMTV-erbB2 mice and measure effects on tumor

  5. MiR-328 May be Considered as an Oncogene in Human Invasive Breast Carcinoma

    PubMed Central

    Saberi, Alihossein; Danyaei, Amir; Neisi, Niloofar; Dastoorpoor, Maryam; Tahmasbi Birgani, Mohammad Javad

    2016-01-01

    Background The recent investigations have rendered microRNAs (miRs) as a novel biomarker in cancer research. In fact, alteration in miR expression may be associated with tumor suppression, tumorigenesis, metastasis, and poor prognosis in human breast cancer (BC). Objectives The aim of this clinical experimental study was to measure the miR-328 expression level in breast cancer tissues, at first. Then, we tried to find out any possible correlation between miR-328 and prognostic and predictive biomarkers in BC. Both of these two objectives were investigated for the first time; and we did not find any similar survey measuring the expression level of miR-328 in both tumor and non-tumor breast tissues. This research was conducted in Iran (Ahvaz, Khuzestan), between December 2013 and April 2014. Furthermore, we did not find any previous document investigating the correlation between miR-328 expression level and prognostic factors in BC. Due to the lack of similar studies intending to measure the expression level of miR-328 in tumor and adjacent non-tumor tissues, we decided to carry out a pilot study. Methods We measured the expression level of miR-328 by Poly (A) real-time PCR based on SYBR Green-I in 28 fresh samples of BC tissues and 28 samples of normal adjacent tissues, including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS). We tried to attribute the results to clinicopathologic features such as status of estrogen and progesterone receptors (ER/PR), HER2/neu (HER2), P53 and also Ki67 labeling (Ki67-LI). Results The results showed that the miR-328 median level of expression was 0.88 (2-ΔΔCt) (25th-75th percentile, 0.07 - 2.34). It means that the expression level increased in tumor tissues compared to normal adjacent tissues (NATs). However, a statistically significant correlation between the miR-328 median expression level and prognostic factors, including pathologic diagnosis, age, and also the status of ER

  6. Cortactin is associated with perineural invasion in the deep invasive front area of laryngeal carcinomas.

    PubMed

    Ambrosio, Eliane Papa; Rosa, Fabíola Encinas; Domingues, Maria Aparecida Custódio; Villacis, Rolando André Rios; Coudry, Renata de Almeida; Tagliarini, José Vicente; Soares, Fernando Augusto; Kowalski, Luiz Paulo; Rogatto, Silvia Regina

    2011-09-01

    The cortactin gene, mapped at 11q13, has been associated with an aggressive clinical course in many cancers because of its function of invasiveness. This study evaluated CTTN protein and its prognostic value in the deep invasive front and superficial areas of laryngeal squamous cell carcinomas. The transcript expression levels were evaluated in a subset of cases. Overexpression of CTTN cytoplasmatic protein (80% of cases in both the deep invasive front and superficial areas) and transcript (30% of samples) was detected in a significant number of cases. In more than 20% of cases, observation verified membrane immunostaining in the deep invasive front and superficial areas. Perineural invasion was significantly associated with N stage and recurrence (P = .0058 and P = .0037, respectively). Higher protein expression levels were correlated with perineural invasion (P = .004) in deep invasive front cells, suggesting that this area should be considered a prognostic tool in laryngeal carcinomas. Although most cases had moderate to strong CTTN expression on the tumor surface, 2 sets of cases revealed a differential expression pattern in the deep invasive front. A group of cases with absent to weak expression of CTTN in the deep invasive front showed good prognosis parameters, and a second group with moderate to strong expression of CTTN were associated with an unfavorable prognosis, suggesting an association with worse outcome. Taken together, these results suggest that the deep invasive front might be considered a grading system in laryngeal carcinomas and that cortactin is a putative marker of worse outcome in the deep invasive front of laryngeal carcinomas.

  7. The angiotensin receptor blocker, Losartan, inhibits mammary tumor development and progression to invasive carcinoma

    PubMed Central

    Coulson, Rhiannon; Liew, Seng H.; Connelly, Angela A.; Yee, Nicholas S.; Deb, Siddhartha; Kumar, Beena; Vargas, Ana C.; O’Toole, Sandra A.; Parslow, Adam C.; Poh, Ashleigh; Putoczki, Tracy; Morrow, Riley J.; Alorro, Mariah; Lazarus, Kyren A.; Yeap, Evie F.W.; Walton, Kelly L.; Harrison, Craig A.; Hannan, Natalie J.; George, Amee J.; Clyne, Colin D.; Ernst, Matthias; Allen, Andrew M.; Chand, Ashwini L.

    2017-01-01

    -associated macrophages in Losartan or vehicle-treated mammary tumors. Analysis of AT1R expression with radiolabelled ligand binding assays in human breast cancer biopsies showed high AT1R levels in 30% of invasive ductal carcinomas analysed. Furthermore, analysis of the TCGA database identified that high AT1R expression to be associated with luminal breast cancer subtype. Our in vivo data and analysis of human invasive ductal carcinoma samples identify the AT1R is a potential therapeutic target in breast cancer, with the availability of a range of well-tolerated inhibitors currently used in clinics. We describe a novel signalling pathway critical in breast tumorigenesis, that may provide new therapeutic avenues to complement current treatments. PMID:28416734

  8. Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma.

    PubMed

    Leav, I; Schelling, K H; Adams, J Y; Merk, F B; Alroy, J

    2001-08-01

    The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and

  9. Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast.

    PubMed

    Li, Shuai; Yang, Cuicui; Zhai, Lili; Zhang, Wenwei; Yu, Jing; Gu, Feng; Lang, Ronggang; Fan, Yu; Gong, Meihua; Zhang, Xiuqing; Fu, Li

    2012-11-01

    Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n = 22) and IDC-NSTs (n = 24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues.

  10. Intra-pancreatic Distal Bile Duct Carcinoma is Morphologically, Genetically, and Clinically Distinct from Pancreatic Ductal Adenocarcinoma.

    PubMed

    Deshpande, Vikram; Konstantinidis, Ioannis T; Castillo, Carlos Fernandez-Del; Hezel, Aram F; Haigis, Kevin M; Ting, David T; Bardeesy, Nabeel; Goyal, Lipika; Zhu, Andrew X; Warshaw, Andrew L; Lillemoe, Keith D; Ferrone, Cristina R

    2016-05-01

    Differentiating intra-pancreatic distal bile duct carcinoma invading the pancreas from pancreatic ductal adenocarcinomas (PDAC) surrounding the distal common bile duct (CBD) can be challenging. Our aim is to identify clinical, morphological, and genetic features characteristic of intra-pancreatic distal bile duct carcinoma. Clinicopathologic data of 550 patients undergoing a pancreaticoduodenectomy between September 1990 and May 2008 were reviewed. KRAS status was assessed with mass-spectrometric genotyping. Ninety-seven patients with intra-pancreatic adenocarcinomas surrounding the CBD were identified; slides were available for 80. Two relationships with the CBD were recognized as follows: type I (n = 42): cancer grew concentrically around the CBD and type II (n = 38): cancer grew asymmetrically around the CBD. Type I adenocarcinomas were associated with high-grade biliary dysplasia (45 vs. 13 %; p = 0.003); type II were associated with high-grade pancreatic intra-epithelial neoplasia (PanIN-2 or -3) (39 vs. 9 %; p = 0.003). Type I tumors had a better median survival (46 months) compared to type II (23 months) or other PDAC (20 months) (p < 0.001). Mutated KRAS was identified in 3/26 (11 %) type I and 20/21 (95 %) type II cancers (p < 0.001). There may be poorer survival in the presence of a KRAS mutation than wild-type KRAS (22.9 vs. 41.6 months; p = 0.3). Distal periductal adenocarcinomas fall into two distinct groups with biologic, morphologic and genetic differences. Those growing symmetrically around the CBD are more likely to be intra-pancreatic distal bile duct carcinomas and are associated with improved survival whereas cancers with asymmetric growth are more likely to have KRAS mutations and to be PDACs. These findings facilitate a more accurate histopathological diagnosis, which could improve patient selection for therapeutic trials.

  11. Gene-expression signature of vascular invasion in hepatocellular carcinoma

    PubMed Central

    Mínguez, Beatriz; Hoshida, Yujin; Villanueva, Augusto; Toffanin, Sara; Cabellos, Laia; Thung, Swan; Mandeli, John; Sia, Daniela; April, Craig; Fan, Jian-Bing; Lachenmayer, Anja; Savic, Radoslav; Roayaie, Sasan; Mazzaferro, Vincenzo; Bruix, Jordi; Schwartz, Myron; Friedman, Scott L.; Llovet, Josep M.

    2013-01-01

    Background & Aims Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30–40% of patients with early tumors, remains elusive. Methods A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. Results A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48–7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17–6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). Conclusions The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies. PMID:21703203

  12. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2.

    PubMed

    Lyons, Traci R; O'Brien, Jenean; Borges, Virginia F; Conklin, Matthew W; Keely, Patricia J; Eliceiri, Kevin W; Marusyk, Andriy; Tan, Aik-Choon; Schedin, Pepper

    2011-08-07

    The prognosis of breast cancer in young women is influenced by reproductive history. Women diagnosed within 5 years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. Here we describe a mouse model of postpartum breast cancer that identifies mammary gland involution as a driving force of tumor progression. In this model, human breast cancer cells exposed to the involuting mammary microenvironment form large tumors that are characterized by abundant fibrillar collagen, high cyclooxygenase-2 (COX-2) expression and an invasive phenotype. In culture, tumor cells are invasive in a fibrillar collagen and COX-2-dependent manner. In the involuting mammary gland, inhibition of COX-2 reduces the collagen fibrillogenesis associated with involution, as well as tumor growth and tumor cell infiltration to the lung. These data support further research to determine whether women at high risk for postpartum breast cancer would benefit from treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) during postpartum involution.

  13. Gastric intramucosal adenocarcinoma with an invasive micropapillary carcinoma component.

    PubMed

    Tanaka, Hiroki; Baba, Youichirou; Sase, Tomohiro; Isono, Yoshiaki; Matsusaki, Shimpei; Saito, Tomonori; Okano, Hiroshi; Mukai, Katsumi; Murata, Tetsuya; Watanabe, Gen

    2015-02-01

    A 70-year-old woman was referred to our hospital because of early gastric cancer (lesser curvature of the antrum, 0-IIc, tub1, 15 mm) and underwent endoscopic submucosal dissection. Microscopically, the lesion was found to be confined to the mucosa, and predominantly composed of well-differentiated tubular adenocarcinoma with a micropapillary component. On immunohistochemical examination, the characteristic "inside-out pattern" of the micropapillary component was observed; thus, we diagnosed the lesion as gastric cancer with a micropapillary component. Invasive micropapillary carcinoma is a rare subtype of gastric carcinoma, and, to our knowledge, this is the first case of invasive micropapillary carcinoma of the stomach confined to the mucosa.

  14. Primary invasive ocular squamous cell carcinoma in a horse.

    PubMed

    Kaps, Simone; Richter, Marianne; Philipp, Martin; Bart, Madeleine; Eule, Corinna; Spiess, Bernhard M

    2005-01-01

    A 12-year-old Haflinger gelding was presented to the veterinary medical teaching hospital of the University of Zurich with a light-pink raised mass on the temporal limbus and conjunctiva of the left eye. Squamous cell carcinoma was confirmed histologically after keratectomy and cryotherapy. Seven months later, a smooth pink, progressively enlarging mass was observed within the cornea of the left eye. Ultrasonographically, the mass was not only infiltrating the corneal stroma but seemed to protrude into the anterior chamber. The globe was surgically removed and submitted for pathology. A histologic diagnosis of corneal ocular squamous cell carcinoma with deep stromal invasion, infiltration of the uveoscleral meshwork and iridocorneal angle and resulting intraocular extension was made. This is the first detailed description of a limbal squamous cell carcinoma with invasion into the cornea and uvea in the horse.

  15. Extramammary Paget’s Disease of Anal Canal Associated With Rectal Adenoma Without Invasive Carcinoma

    PubMed Central

    Chumbalkar, Vaibhav; Jennings, Timothy A.; Ainechi, Sanaz; Lee, Edward C.; Lee, Hwajeong

    2016-01-01

    Extramammary Paget’s disease (EMPD) is a rare disease which is found in apocrine-rich locations such as anogenital region, axilla and rarely in other sites. Perianal EMPD is often reported as the involvement of perianal skin, but involvement of anal mucosa is very rare. Based on pathogenesis and association with either synchronous or metachronous malignancy, EMPD can be divided into primary and secondary types. Treatment approach for these two types of Paget’s disease and their prognosis is different, thus it is important to make the distinction. Secondary type of Paget’s disease is almost always described in association with invasive malignancy. While secondary Paget’s disease arising in association with ductal carcinoma in situ of the breast is common, secondary EMPD associated with precursor lesion of the rectum without invasion is exceedingly rare. We report a very rare case of secondary Paget’s disease of the anal canal in association with rectal tubular adenoma (precursor lesion) without malignancy. PMID:28058078

  16. Management of atypical lobular hyperplasia, atypical ductal hyperplasia, and lobular carcinoma in situ.

    PubMed

    Clauser, Paola; Marino, Maria A; Baltzer, Pascal A T; Bazzocchi, Massimo; Zuiani, Chiara

    2016-01-01

    Atypical hyperplasia and lobular carcinoma in situ are rare proliferative breast lesions, growing inside ducts and terminal ducto-lobular units. They represent a marker of increased risk for breast cancer and a non-obligate precursor of malignancy. Evidence available on diagnosis and management is scarce. They are frequently found incidentally associated with other lesions, but can be visible through mammography, ultrasound or magnetic resonance. Due to the risk of underestimation, surgical excision is often performed. The analysis of imaging and histopathological characteristics could help identifying low-risk cases, for which surgery is not necessary. Chemopreventive agents can be used for risk reduction. Careful imaging follow up is mandatory; the role of breast MRI as screening modality is under discussion.

  17. Fine-needle aspiration of gray zone lesions of the breast: fibroadenoma versus ductal carcinoma.

    PubMed

    Jing, Xin; Normolle, Daniel; Michael, Claire W

    2013-09-01

    While breast lesions have characteristic cytological features, some lesions, particularly adenocarcinoma and fibroadenoma, may present with overlapping features causing erroneous diagnoses. The current study aimed to define significant cytomorphologic features predictive of fibroadenoma and adenocarcinoma, respectively. Further, we intended to evaluate the predictive characteristics for differentiation between gray zone lesions and to identify root causes contributing to misdiagnoses. First, direct smears prepared from 14 histology-confirmed fibroadenomas and 14 adenocarcinomas were reviewed and characteristics of commonly encountered morphologic features were assessed. We then retrospectively and blindly reviewed nine cytohistologic discrepant cases using the significant characteristic as a guideline, in order to assess whether these discrepant cases could be correctly categorized. Morphologic characteristics predictive of fibroadenoma included moderate cellularity, large, folded cellular sheets/aggregates, staghorn projections, smooth and round borders, monolayers, honeycomb arrangement, smaller nuclear size, and background bipolar cells. Predictive characteristics of adenocarcinoma included high cellularity, loose cohesive sheets/aggregates, pointed projections, irregular borders, larger nuclear size, irregular nuclear membrane, prominent nucleoli, and single atypical epithelial cells. Retrospective, blind review correctly re-classified seven out of nine cytohistologic discrepant cases, including five false negative cases and two false positive cases. Root causes contributing to the misdiagnoses were large branching sheets of carcinoma mimicking folded sheets of fibroadenoma; fibroblasts mimicking myoepithelial cells; apocrine cells mimicking carcinoma cells; and not recognizing the loose myxoid matrix presenting as soap bubbles in fibroadenoma. In conclusion, this study identified significant characteristics that can assist in achieving accurate diagnosis in a

  18. Immunohistochemical Markers Distinguishing Cholangiocellular Carcinoma (CCC) from Pancreatic Ductal Adenocarcinoma (PDAC) Discovered by Proteomic Analysis of Microdissected Cells.

    PubMed

    Padden, Juliet; Ahrens, Maike; Kälsch, Julia; Bertram, Stefanie; Megger, Dominik A; Bracht, Thilo; Eisenacher, Martin; Kocabayoglu, Peri; Meyer, Helmut E; Sipos, Bence; Baba, Hideo A; Sitek, Barbara

    2016-03-01

    Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types that arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvable issue for pathologists. The detection of biomarkers with high specificity and sensitivity for the differentiation of these tumor types would therefore be a valuable tool. Here, we address this problem by comparing microdissected CCC and PDAC tumor cells from nine and eleven cancer patients, respectively, in a label-free proteomics approach. The novel biomarker candidates were subsequently verified by immunohistochemical staining of 73 CCC, 78 primary, and 18 metastatic PDAC tissue sections. In the proteome analysis, we found 180 proteins with a significantly differential expression between CCC and PDAC cells (p value < 0.05, absolute fold change > 2). Nine candidate proteins were chosen for an immunohistochemical verification out of which three showed very promising results. These were the annexins ANXA1, ANXA10, and ANXA13. For the correct classification of PDAC, ANXA1 showed a sensitivity of 84% and a specificity of 85% and ANXA10 a sensitivity of 90% at a specificity of 66%. ANXA13 was higher abundant in CCC. It presented a sensitivity of 84% at a specificity of 55%. In metastatic PDAC tissue ANXA1 and ANXA10 showed similar staining behavior as in the primary PDAC tumors (13/18 and 17/18 positive, respectively). ANXA13, however, presented positive staining in eight out of eighteen secondary PDAC tumors and was therefore not suitable for the differentiation of these from CCC. We conclude that ANXA1 and ANXA10 are promising biomarker candidates with high diagnostic values for the differential diagnosis of intrahepatic CCC and metastatic liver tumors deriving from PDAC. © 2016 by The American Society for Biochemistry

  19. Immunohistochemical Markers Distinguishing Cholangiocellular Carcinoma (CCC) from Pancreatic Ductal Adenocarcinoma (PDAC) Discovered by Proteomic Analysis of Microdissected Cells*

    PubMed Central

    Padden, Juliet; Ahrens, Maike; Kälsch, Julia; Bertram, Stefanie; Megger, Dominik A.; Bracht, Thilo; Eisenacher, Martin; Kocabayoglu, Peri; Meyer, Helmut E.; Sipos, Bence; Baba, Hideo A.; Sitek, Barbara

    2016-01-01

    Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types that arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvable issue for pathologists. The detection of biomarkers with high specificity and sensitivity for the differentiation of these tumor types would therefore be a valuable tool. Here, we address this problem by comparing microdissected CCC and PDAC tumor cells from nine and eleven cancer patients, respectively, in a label-free proteomics approach. The novel biomarker candidates were subsequently verified by immunohistochemical staining of 73 CCC, 78 primary, and 18 metastatic PDAC tissue sections. In the proteome analysis, we found 180 proteins with a significantly differential expression between CCC and PDAC cells (p value < 0.05, absolute fold change > 2). Nine candidate proteins were chosen for an immunohistochemical verification out of which three showed very promising results. These were the annexins ANXA1, ANXA10, and ANXA13. For the correct classification of PDAC, ANXA1 showed a sensitivity of 84% and a specificity of 85% and ANXA10 a sensitivity of 90% at a specificity of 66%. ANXA13 was higher abundant in CCC. It presented a sensitivity of 84% at a specificity of 55%. In metastatic PDAC tissue ANXA1 and ANXA10 showed similar staining behavior as in the primary PDAC tumors (13/18 and 17/18 positive, respectively). ANXA13, however, presented positive staining in eight out of eighteen secondary PDAC tumors and was therefore not suitable for the differentiation of these from CCC. We conclude that ANXA1 and ANXA10 are promising biomarker candidates with high diagnostic values for the differential diagnosis of intrahepatic CCC and metastatic liver tumors deriving from PDAC. PMID:26644413

  20. Outcomes of Low-Risk Ductal Carcinoma In Situ in Southeast Asian Women Treated With Breast Conservation Therapy

    SciTech Connect

    Wong, Fuh Yong; Wang, Fuqiang; Chen, John Ju; Tan, Chiew Har; Tan, Puay Hoon

    2014-04-01

    Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.

  1. Detection of serum VEGF and MMP-9 levels by Luminex multiplexed assays in patients with breast infiltrative ductal carcinoma

    PubMed Central

    ZHANG, JUNYING; YIN, LI; WU, JIANZHONG; ZHANG, YE; XU, TAO; MA, RONG; CAO, HAIXIA; TANG, JINHAI

    2014-01-01

    The aim of the present study was to assess the effect of the combined detection of serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) by Luminex multiplexed assays for the diagnosis, treatment and prognosis of breast cancer. Preoperative levels of serum VEGF and MMP-9 were detected via a lipid chip-based method in 301 breast cancer cases, 83 breast fibroadenoma cases and 40 healthy adults. Postoperative levels of VEGF and MMP-9 were also detected in 118 breast cancer cases. The levels of serum VEGF and MMP-9 in patients with breast infiltrative ductal carcinoma (IDC) were higher than those in the breast fibroadenoma and healthy control groups (P<0.05); there was no statistically significant difference between the breast fibroadenoma and healthy groups (P>0.05). The levels of VEGF and MMP-9 were shown to correlate with the clinical stage, tumor size and the lymph node metastasis status. However, the levels were not associated with age or gender (P>0.05). In addition, the serum level of MMP-9 exhibited a significantly correlation with the VEGF level (r=0.601, P<0.001). Subgroup analysis revealed that in patients with IDC, serum levels of VEGF and MMP-9 prior to surgery were significantly higher than those following surgery (P<0.05). Therefore, the serum levels of VEGF and MMP-9 can be used as markers for the diagnosis of breast IDC and may also be valuable for the prediction of lymph nodes metastasis. PMID:24944618

  2. Pure ductal carcinoma in situ: kinetic and morphologic MR characteristics compared with mammographic appearance and nuclear grade.

    PubMed

    Jansen, Sanaz A; Newstead, Gillian M; Abe, Hiroyuki; Shimauchi, Akiko; Schmidt, Robert A; Karczmar, Gregory S

    2007-12-01

    To retrospectively compare the kinetic and morphologic characteristics of pure ductal carcinoma in situ (DCIS) lesions depicted on dynamic contrast material-enhanced magnetic resonance (MR) images with the nuclear grade and conventional mammographic appearance of these lesions. This HIPAA-compliant retrospective study was institutional review board approved, and informed patient consent was waived. Seventy-eight patients with 79 histologically proved pure DCIS lesions were selected. There were 17 low-nuclear-grade, 26 intermediate-nuclear-grade, 30 high-nuclear-grade, and six unclassified lesions. Sixty-five lesions were classified as fine pleomorphic, fine linear, or fine linear-branching calcifications (n = 31); amorphous or indistinct calcifications (n = 18); noncalcified mass (n = 10); or occult (n = 6) at conventional (x-ray) mammography. One experienced radiologist analyzed lesion morphology and kinetic curve shape according to the Breast Imaging Reporting and Data System lexicon. Initial enhancement percentage, time to peak enhancement (T(peak)), and signal enhancement ratio (a measure of washout) were calculated for each lesion. Of the 79 pure DCIS lesions, 20 (25%) exhibited enhancement plateau curves and 35 (44%) exhibited washout curves. The lesions with a masslike appearance on mammograms exhibited more suspicious kinetic characteristics (mean T(peak) approximately 2 minutes) than did the lesions with amorphous or indistinct calcifications (mean T(peak) = 4.4 minutes). There was no significant difference in enhancement kinetic properties across the nuclear grades. Lesion morphology was predominantly nonmass, with clumped or heterogeneous enhancement in a segmental or linear distribution. The pure DCIS lesions exhibited washout, plateau, and persistent enhancement curves. Enhancement kinetic characteristics varied with mammographic appearance but not with nuclear grade. http://radiology.rsnajnls.org/cgi/content/full/245/3/684/DC1. (c) RSNA, 2007.

  3. Cytokine profiles of tumor supernatants in invasive ductal cancer and fibroadenoma of the breast and its relationship with VEGF-A expression in the tumors.

    PubMed

    Autenshlyus, Alexander I; Arkhipov, Sergey A; Kunts, Tatiana A; Marinkin, Igor O; Mikhailova, Elena S; Karpukhina, Xenia V; Varaksin, Nikolay A

    2017-03-01

    Interrelations between cytokines, produced by invasive ductal carcinoma (IDC) and fibroadenoma (FA) of the breast, and angiogenic growth factor VEGF-A, expressed in IDC and FA, were investigated. The analysis of the cytokine profiles of IDC and FA was performed by cultivation of tumor biopsy specimens in vitro. Testing of the cytokine-producing reserve of the tumors for production of VEGF-A was conducted by culturing samples of IDC and FA in a medium containing polyclonal activator (a complex of phytohemagglutinin, concanavalin A, and lipopolysaccharide). Levels of cytokines and growth factors (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A) and MCP-1 (monocyte chemoattractant protein-1) in tumor supernatants were determined by an ELISA. Expression of VEGF-A was analyzed in tumor biopsy specimens by immunohistochemical analysis. In the IDC supernatants, the concentrations of IL-17, IL-18, and IFN-γ were higher and the concentrations of IL-10 and MCP-1 were lower in comparison with the FA supernatants. We observed negative correlations between the macrophage infiltration and VEGF-A concentration in the IDC supernatants (r = -0.508; P = 0.011) and between VEGF-A expression and the IDC vascularization degree (r = -0.423, P = 0.039). Spontaneous expression of VEGF-A in samples of IDC significantly exceeded the VEGF-A expression in FA. There was no difference between IDC and FA in VEGF-A expression after treatment with the polyclonal activators. Our results indicate that greater malignancy may have a paradoxical effect that is controlled by cytokines and characterized by weakening of tumor angiogenesis during overproduction of VEGF-A. These findings point to complex mechanisms of positive and negative regulation of tumor angiogenesis by cytokines that are produced by the tumor and by cells in its microenvironment, whose cytokine profiles may change at different stages of tumor progression.

  4. Negative estrogen-receptor invasive breast carcinoma: mammographic aspects, correlations with HER2/neu oncoprotein status.

    PubMed

    Enache, Dana Elena; Georgescu, Claudia Valentina; Pătrană, Nicoleta

    2012-01-01

    This study involved 40 ER-negative female patients with invasive breast cancer, aged between 25 and 88 years, diagnosed at Emergency County Hospital of Craiova, Romania, during a two-year interval (2010-2011). All patients that took part in the study were subjected to a preoperative mammography exam, and later to HP and IHC exams, in order to detect the ER, PR and HER2 status. These exams were followed by CISH in ambiguous HER2 cases. The tumor detection method was palpation in 16 cases, whereas in 24 cases the method used was the screening mammography. Histopathologically, the analyzed tumors were infiltrative ductal carcinoma (35 cases), lobular carcinoma (one case), mucinous (two cases) and metaplastic carcinoma (two cases). Depending on the status of the oncoprotein HER2, the 40 ER-negative female patients included in the study formed two groups: the ER-negative, HER2-positive (11 cases, 27.5%) formed the first group and the ER-negative, HER2-negative (29 cases, 72.5%) formed the second group. Depending on the expression of the receptors for progesterone, 60% of cases were classified as triple negative mammary carcinomas (ER-, PR-, HER2-). The comparative study of the ER-negative, HER2-positive and the ER-negative, HER2-negative mammary carcinomas showed that the tumors of the ER-negative, HER2-positive group were mostly high degree cancers (80% vs. 56%), with negative progesterone receptors (81.81% vs. 48.27%), associated with axillary lymph node metastasis (63.63% vs. 48.27%), and were detected at a higher cancer stage (II/III) (81.81% vs. 62.06%). Regarding the mammographic features, the ER-negative HER2-positive breast cancers are more likely to be irregular masses (62.5% vs. 33.33%), with spiculated margins (45.45% vs. 6.9%), frequently associated with dense or heterogeneously dense breast (82% vs. 69%) and pleomorphic calcifications (62.5% vs. 28.57%) comparative with ER-negative HER2-negative cancers that were more frequently round/oval mass, with

  5. Adhesion systems in normal breast and in invasive breast carcinoma.

    PubMed Central

    Glukhova, M.; Koteliansky, V.; Sastre, X.; Thiery, J. P.

    1995-01-01

    To analyze the role of various elements of the adhesion system in the organization of the normal mammary gland and in breast carcinoma, we have studied simultaneously the expression of integrins, E- and P-cadherins, and cytoplasmic constituents of adherens junctions. In the normal gland, E-cadherin and alpha-catenin are present in luminal epithelial and myoepithelial cells, whereas integrins are more abundant in acinar epithelial and in myoepithelial cells. We demonstrate here that, in addition, myoepithelial cells express much more vinculin and alpha-actinin than luminal epithelial cells, whereas talin and focal adhesion kinase (pp125FAK) are restricted to the basal cell layer. In invasive carcinoma, E-cadherin is usually present although often in reduced amount; different integrin subunits are expressed either by a fraction or by all of the cells or are absent. However, the cytoplasmic components of adherens junctions, such as alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK, are expressed at low levels or cannot be detected in the carcinoma cells. Our data suggest that 1), in the normal mammary gland, the myoepithelial cells, being particularly rich in integrins and cytoplasmic components of the adherens junctions, play an important role in the maintenance of tissue integrity; 2), in invasive carcinoma, cell aggregates may be maintained due to varying levels of expression of E-cadherin and/or integrins; and 3), interaction of the transmembrane adhesion molecules with the cytoskeleton in carcinoma may be impaired as revealed by reduced levels of expression of alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK. Importantly, carcinoma cells, when exposed to stroma during invasion, do not acquire the adhesion apparatus characteristic of normal cells in contact with the extracellular matrix. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7887451

  6. Ductal Breast Carcinoma In Situ: Mammographic Features and Its Relation to Prognosis and Tumour Biology in a Population Based Cohort

    PubMed Central

    Sollie, Thomas; Blomqvist, Carl; Abdsaleh, Shahin; Liljegren, Göran

    2017-01-01

    Casting-type calcifications and a histopathological picture with cancer-filled duct-like structures have been presented as breast cancer with neoductgenesis. We correlated mammographic features and histopathological neoductgenesis with prognosis in a DCIS cohort with long follow-up. Mammographic features were classified into seven groups according to Tabár. Histopathological neoductgenesis was defined by concentration of ducts, lymphocyte infiltration, and periductal fibrosis. Endpoints were ipsilateral (IBE) in situ and invasive events. Casting-type calcifications and neoductgenesis were both related to high nuclear grade, ER- and PR-negativity, and HER2 overexpression but not to each other. Casting-type calcifications and neoductgenesis were both related to a nonsignificant lower risk of invasive IBE, HR 0.38 (0.13–1.08) and 0.82 (0.29–2.27), respectively, and the HR of an in situ IBE was 0.90 (0.41–1.95) and 1.60 (0.75–3.39), respectively. Casting-type calcifications could not be related to a worse prognosis in DCIS. We cannot explain why a more aggressive phenotype of DCIS did not correspond to a worse prognosis. Further studies on how the progression from in situ to invasive carcinoma is driven are needed. PMID:28286675

  7. Invasive lobular carcinoma of the breast: MRI pathological correlation following bilateral total mastectomy.

    PubMed

    Stivalet, Aude; Luciani, Alain; Pigneur, Frederic; Dao, Thu Ha; Beaussart, Pauline; Merabet, Zahira; Perlbarg, Julie; Meyblum, Evelyne; Baranes, Laurence; Calitchi, Elie; Lepage, Christophe; Belkacemi, Yazid; Lagrange, Jean-Leon; Lantieri, Laurent; Rahmouni, Alain

    2012-05-01

    Invasive lobular carcinoma (ILC) is more often multifocal and bilateral than invasive ductal carcinoma. MRI is usually recommended for detection of all ILC sites. The performance of known diagnostic breast MRI criteria for ILC characterization has not been evaluated to date using bilateral mastectomy specimens as gold standard. To determine the value of BI-RADS 2006 MRI criteria for ILC detection and characterization, using pathological examination of bilateral mastectomy specimens as the reference standard. Between 2004 and 2007, we retrospectively included all patients with pathologically documented ILC referred to our institution for bilateral mastectomy and preoperative bilateral breast MRI. The location, diameter, and characteristics (BI-RADS) of all lesions were compared with pathological findings. The sensitivity and positive predictive value of bilateral breast MRI for the diagnosis of ILC were calculated. Association of MRI BI-RADS categorical variables and characterization of ILC were assessed (Fisher exact test). Among 360 patients treated for ILC in 2004-2007, 15 patients qualified for this study. Thirty-one ILC foci were found on pathological examination (30 ipsilateral and 1 contralateral tumor; mean diameter 23 mm; range 2-60 mm) and all were identified on MRI, with 90% of masses and 10% non-mass-like enhancements; MRI features significantly associated with ILC included absence of smooth margins (P = 0.02) and rim-shaped enhancement (P = 0.039). Enhancement kinetics of the 31 foci were evenly distributed among wash-out, plateau, and persistent profiles. Eleven additional lesions were seen on MRI, mainly corresponding to fibrocystic disease; 91% presented as masses and 9% had a wash-out profile. Based on the 2006 BI-RADS criteria, breast MRI shows a high sensitivity for ILC detection, at the expense of a 26% false-positive rate, suggesting that a pathological proof by US- or MR-guided biopsy is required in case of suspicious MRI images in this context.

  8. [Hepatocellular carcinoma with cardiovascular invasion. Report of five cases].

    PubMed

    Valera, José M; Merino, Roberto; Palavecino, Patricio; Sepúlveda, Luis; Smok, Gladys; Fernández, Manuel; Brahm, Javier

    2004-12-01

    The diagnosis of hepatocellular carcinoma in cirrhotic patients has increased, mainly due to early detection using newer imaging techniques. The therapeutic approach depends on the tumor staging and the liver function. Cardiac involvement has a very bad prognosis. We report three males aged 59, 75 and 76 years and two females, aged 64 and 79 years. All had cirrhosis of diverse aetiologies with hepatocellular carcinoma and tumoral invasion of the inferior vena cava and right atrium. Three patients died during hospital stay and two were discharged for conservative management at home. This rare complication has to be considered in cirrhosis.

  9. Mucinous breast carcinomas lack PIK3CA and AKT1 mutations.

    PubMed

    Kehr, Elizabeth L; Jorns, Julie M; Ang, Daphne; Warrick, Andrea; Neff, Tanaya; Degnin, Michelle; Lewis, Rebecca; Beadling, Carol; Corless, Christopher L; Troxell, Megan L

    2012-12-01

    Activating point mutations in the phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) are among the most common molecular defects in invasive breast cancer. Point mutations in the downstream kinase AKT1 are seen in a minority of carcinomas. These mutations are found preferentially in estrogen receptor-positive and Her2-positive breast carcinomas; however, special morphologic types of breast cancer have not been well studied. Twenty-nine cases of pure invasive mucinous carcinoma and 9 cases of ductal carcinoma with mucinous differentiation were screened for a panel of point mutations (>321 mutations in 30 genes) using a multiplex polymerase chain reaction panel with mass spectroscopy readout. In addition, associated ductal carcinoma in situ, hyperplasia, or columnar cell lesions were separately tested where available (25 lesions). In 3 invasive cases and 15 ductal carcinoma in situ/proliferative lesions, PIK3CA hotspot mutations were, instead, tested by direct sequencing. No point mutations were identified in invasive mucinous breast carcinoma. This contrasts with the 35% frequency of PIK3CA mutations in a comparative group of invasive ductal carcinomas of no special type. Interestingly, PIK3CA hotspot point mutations were identified in associated ductal carcinoma in situ (3/14) and hyperplasia (atypical ductal hyperplasia [2/3], usual ductal hyperplasia [2/3], columnar cell change [1/5]), suggesting that PIK3CA mutations may play a role in breast epithelial proliferation. This series represents the largest study, to date, of PIK3CA genotyping in mucinous carcinoma and supports the unique pathogenetics of invasive mucinous breast carcinoma.

  10. Management of periorbital basal cell carcinoma with orbital invasion.

    PubMed

    Sun, Michelle T; Wu, Albert; Figueira, Edwin; Huilgol, Shyamala; Selva, Dinesh

    2015-11-01

    Basal cell carcinoma (BCC) is the most common eyelid malignancy; however, orbital invasion by periocular BCC is rare, and management remains challenging. Established risk factors for orbital invasion by BCC include male gender, advanced age, medial canthal location, previous recurrences, large tumor size, aggressive histologic subtype and perineural invasion. Management requires a multidisciplinary approach with orbital exenteration remaining the treatment of choice. Globe-sparing treatment may be appropriate in selected patients and radiotherapy and chemotherapy are often used as adjuvant therapies for advanced or inoperable cases, although the evidence remains limited. We aim to summarize the presentation and treatment of BCC with orbital invasion to better guide the management of this complex condition.

  11. Histogenesis of metaplastic breast carcinoma and axillary nodal metastases.

    PubMed

    Osako, Tomo; Horii, Rie; Ogiya, Akiko; Iijima, Kotaro; Iwase, Takuji; Akiyama, Futoshi

    2009-02-01

    A 40-year-old breast-feeding woman presented with left breast swelling. On physical examination a 7 cm mass was found in the breast. Because biopsy demonstrated malignant tissue, mastectomy with axillary nodal dissection was performed. Pathological findings were consistent with metaplastic breast carcinoma with nodal metastases. The primary tumor consisted of three types of invasion: ductal, squamous, and sarcomatous. Furthermore, three morphological transitions were observed: ductal-squamous, ductal-sarcomatous, and squamous-sarcomatous. Ductal-squamous (12/18 microscopy slides) and squamous-sarcomatous transitions (10/18) were more commonly observed than ductal-sarcomatous transition (3/18). Furthermore, immunohistochemistry showed loss of epithelial marker (cytokeratin) and acquisition of mesenchymal markers (vimentin and alpha-smooth muscle actin) in the sarcomatous component. These findings suggested that epithelial-mesenchymal transition had occurred in the tumor and that two pathways, ductal-squamous-sarcomatous and ductal-sarcomatous transition, were involved in progression of metaplastic breast carcinoma. The main pathway appeared to be ductal-squamous-sarcomatous transition. Regarding the nodal metastases, of 13 positive nodes, ductal, squamous, and sarcomatous components were observed in 13, seven, and two nodes, respectively. Moreover, as in the primary tumor, ductal-squamous and squamous-sarcomatous transitions were observed. This suggested that the ductal component metastasized to the nodes and that epithelial-mesenchymal transition subsequently occurred within the nodes.

  12. Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma.

    PubMed

    Park, Hyung Kyu; Lee, Kyung-Yung; Yoo, Moon-Won; Hwang, Tae Sook; Han, Hye Seung

    2016-06-01

    Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005-2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.

  13. Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.

    PubMed

    Haffner, Michael C; Weier, Christopher; Xu, Meng Meng; Vaghasia, Ajay; Gürel, Bora; Gümüşkaya, Berrak; Esopi, David M; Fedor, Helen; Tan, Hsueh-Li; Kulac, Ibrahim; Hicks, Jessica; Isaacs, William B; Lotan, Tamara L; Nelson, William G; Yegnasubramanian, Srinivasan; De Marzo, Angelo M

    2016-01-01

    Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for

  14. Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration.

    PubMed

    Pignatelli, Jeanine; Goswami, Sumanta; Jones, Joan G; Rohan, Thomas E; Pieri, Evan; Chen, Xiaoming; Adler, Esther; Cox, Dianne; Maleki, Sara; Bresnick, Anne; Gertler, Frank B; Condeelis, John S; Oktay, Maja H

    2014-11-25

    Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)-responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding Mena(INV), an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena(INV) or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that Mena(INV) and TMEM frequency are correlated prognostic markers and CSF-1 and Mena(INV) may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes.

  15. Primary mucinous carcinoma with direct histopathologic evidence of lymphatic invasion.

    PubMed

    Warycha, Melanie; Kamino, Hideko; Mobini, Narciss; Hale, Elizabeth K

    2006-01-01

    Primary mucinous carcinoma of the skin is a rare sweat gland neoplasm which occurs most commonly in the periorbital region. Although the tumor has a propensity for local recurrence and regional spread, distant metastases are rare. The standard treatment of primary mucinous carcinoma is wide local excision. Mohs micrographic surgery may also be utilized in cases where tissue conservation is of utmost concern. We present a case of primary mucinous carcinoma arising in the scalp, which was treated with wide local excision. A case report and literature review are presented. Histopathologic evaluation revealed a well-circumscribed neoplasm characterized by lobules and aggregates of epithelial cells embedded in abundant pools of mucin. In addition, small aggregates of neoplastic cells were found at a distance from the primary nodule, indicative of lymphatic invasion. Primary mucinous carcinoma has a high propensity for locoregional metastases and recurrence. To our knowledge, this is the first report demonstrating direct histopathologic evidence of lymphatic invasion which correlates with this tumor's biologic behavior.

  16. Renal cell carcinoma with vascular invasion: Mortality and prognostic factors.

    PubMed

    Rodríguez-Cabello, M A; Laso-García, I; Donis-Canet, F; Gómez-Dos-Santos, V; Varona-Crespo, C; Burgos-Revilla, F J

    2017-03-01

    Analysis of the results of patients who had been operated of renal cell carcinoma with vascular invasion in our institution, evaluation of prognostic factors and complications. Retrospective observational study of 37 patients diagnosed of renal cell carcinoma with vascular invasion operated between May 1999 and July 2013. We used the method of Kaplan-Meier survival analysis and the Mantel-Haenszel's test (log rank) and the Cox's proportional hazards analysis test to analyse the risk factors of mortality. The median age was 60 years. Mean follow-up period was 42.1 months. The median overall survival and disease-free survival were 53.8and 36.3 months, respectively. There was statistical association between overall survival and ASA (p=0.047), tumor stage (p=0.003), lymph node involvement (p=0.024), presence of metastases (p=0.013), level of tumor thrombus (p=0, 05) and histological type (p=0.001). 14 patients had grade IIIb complications or higher according to the Clavien Dindo classification, the most frequent was bleeding. Renal cell carcinoma with vascular invasion is a disease with high rate of mortality. Surgery is a therapeutic option that can be curative. The number of complications is important. Survival is conditioned by the ASA, tumor stage, the level of tumor thrombus, lymph node involvement, metastasis and histological type. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Ductal Carcinoma In Situ With Microinvasion: Prognostic Implications, Long-Term Outcomes, and Role of Axillary Evaluation

    SciTech Connect

    Parikh, Rahul R.; Haffty, Bruce G.; Lannin, Donald; Moran, Meena S.

    2012-01-01

    Purpose: To compare the clinical-pathologic features and long-term outcomes for women with ductal carcinoma in situ (DCIS) vs. DCIS with microinvasion (DCISM) treated with breast conservation therapy (BCT), to assess the impact of microinvasion. Patients and Methods: A total of 393 patients with DCIS/DCISM from our database were analyzed to assess differences in clinical-pathologic features and outcomes for the two cohorts. Results: The median follow-up was 8.94 years, and the mean age was 55.8 years for the entire group. The DCISM cohort was comprised of 72 of 393 patients (18.3%). Surgical evaluation of the axilla was performed in 58.3% (n = 42) of DCISM vs. 18.1% (n = 58) of DCIS, with only 1 of 42 DCISM (2.3%) vs. 0 of 58 DCIS with axillary metastasis. Surgical axillary evaluation was not an independent predictor of local-regional relapse (LRR), distant relapse-free survival (DRFS), or overall survival (OS) in Cox proportional hazards analysis (p > 0.05). For the DCIS vs. DCISM groups, respectively, the 10-year breast relapse-free survival was 89.0% vs. 90.7% (p = 0.36), DRFS was 98.5% vs. 97.9% (p = 0.78), and OS was 93.2% vs. 95.7% (p = 0.95). The presence of microinvasion did not correlate with LRR, age, presentation, race, family history, margin status, and use of adjuvant hormonal therapy (all p > 0.05). In univariate analysis, pathology (DCIS vs. DCISM) was not an independent predictor of LRR (hazard ratio [HR], 1.58; 95% confidence interval [CI], 0.58-4.30; p = 0.36), DRFS (HR, 0.72; 95% CI, 0.07-6.95; p = 0.77), or OS (HR, 1.03; 95% CI, 0.28-3.82; p = 0.95). Conclusions: Our data imply that the natural history of DCISM closely resembles that of DCIS, with a low incidence of local-regional and distant failures. On the basis of our large dataset, the incidence of axillary metastasis in DCISM appears to be small and not appear to correlate to outcomes, and thus, microinvasion alone should not be the sole criterion for more aggressive treatment.

  18. RTOG 9804: A Prospective Randomized Trial for Good-Risk Ductal Carcinoma In Situ Comparing Radiotherapy With Observation

    PubMed Central

    McCormick, Beryl; Winter, Kathryn; Hudis, Clifford; Kuerer, Henry Mark; Rakovitch, Eileen; Smith, Barbara L.; Sneige, Nour; Moughan, Jennifer; Shah, Amit; Germain, Isabelle; Hartford, Alan C.; Rashtian, Afshin; Walker, Eleanor M.; Yuen, Albert; Strom, Eric A.; Wilcox, Jeannette L.; Vallow, Laura A.; Small, William; Pu, Anthony T.; Kerlin, Kevin; White, Julia

    2015-01-01

    Purpose The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation. Patients and Methods This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method. Results Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients. Conclusion In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted. PMID:25605856

  19. Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma.

    PubMed

    Martin, Tracey Amanda; Jiang, Wen Guo

    2014-01-01

    The tumor stem cell theory could explain how patients with metastatic disease show clinical relapse several months after starting treatment due to the survival of a small group of cells with unique characteristics. We examined the distribution and expression of a panel of stem cell markers in human breast cancer primary tumors. Human breast tissues were processed for immunohistochemistry, and RNA was extracted for analysis by quantitative-PCR. Immunohistochemical assay revealed that CD44 was strongly expressed in background endothelia and epithelia. CD133 expression was lost in tumor-associated endothelial cells. Conversely, CD49b was strongly stained in the tumors, associated vessels and ducts but was weakly stained in the background epithelia. q-PCR analysis revealed that CD44 and PSCA were reduced in patients with poor outcome (metastatic disease and death from breast cancer), with a marked reduction in ductal carcinoma, particularly with metastasis to bone although these did not reach significant difference. CD133 was significantly reduced in patients with metastatic disease and was also significantly reduced in patients with ductal carcinoma/bone metastasis. Conversely, CD49F was increased in patients with a poor outcome and those with ductal cancer and bone metastases. This is the first study to determine the distribution and expression pattern of these stem cell markers in human breast cancer. There was a significant association between loss of expression and metastatic disease in patients with breast cancer. Such differential expression may play a part in breast cancer disease progression, and suggests that the current stem cell theory may not hold true for all cancer types.

  20. Ductal Carcinoma In Situ of the Breast: Evaluating the Role of Radiation Therapy in the Management and Attempts to Identify Low-risk Patients.

    PubMed

    Shah, Chirag; Vicini, Frank A; Berry, Sameer; Julian, Thomas B; Wilkinson, John Ben; Shaitelman, Simona F; Khan, Atif; Finkelstein, Steven E; Goldstein, Neal

    2015-10-01

    Ductal carcinoma in situ of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with ductal carcinoma in situ include mastectomy or breast-conserving therapy. Although several randomized trials have confirmed a >50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared with breast-conserving surgery alone, controversy persists regarding whether or not RT is needed in selected "low-risk" patients. Over the past two decades, two prospective single-arm studies and one randomized trial have been performed and confirm that the omission of RT after surgery is associated with higher rates of local recurrence even after selecting patients with optimal clinical and pathologic features. Importantly, these trials have failed to consistently and reproducibly identify a low-risk cohort of patients (based on clinical and pathologic features) that does not benefit from RT. As a result, adjuvant RT is still advocated in the majority of patients, even in low-risk cases. Future research is moving beyond traditional clinical and pathologic risk factors and instead focusing on approaches such as multigene assays and biomarkers with the hopes of identifying truly low-risk patients who may not require RT. However, recent studies confirm that even low-risk patients identified from multigene assays have higher rates of local recurrence with local excision alone than would be expected with the addition of RT.

  1. Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis.

    PubMed

    Charalampoudis, P; Agrogiannis, G; Kontzoglou, K; Kouraklis, G; Sotiropoulos, G C

    2017-08-01

    In breast cancer, hormonal receptors hold promise for developing novel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear. We studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters. TRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, or among different hormonal profiles and intrinsic subtypes. This is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  2. Expression and Clinical Significance of Metalloproteases and Their Inhibitors by Endothelial Cells From Invasive Breast Carcinomas.

    PubMed

    Cid, Sandra; Eiro, Noemi; González, Luis O; Beridze, Nana; Vazquez, Julio; Vizoso, Francisco J

    2016-08-01

    Given that tumor blood vessels are important in tumor progression and metastasis, tumor endothelial cells (ECs) are the main targets of antiangiogenic therapy. The aim of the present work was to evaluate the phenotype of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) from ECs at the tumor center and its relationship to MMP/TIMP global expression and its relationship to the occurrence of distant metastasis. An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs (MMP-2, -7, -9, -11, -13, and -14) and TIMPs (TIMP-1, -2, and -3) at the tumor center in 104 patients with primary ductal invasive breast tumors. MMP-11 expression by ECs was related to shorter relapse-free survival, whereas TIMP-3 expression was related to low occurrence of distant metastasis. In addition, MMP-11 and TIMP-2 expression by ECs was associated with shorter overall survival, whereas TIMP-3 expression by ECs was associated with longer overall survival. Our findings indicate significant relationships between the expression of MMPs/TIMPs by ECs and the global expression of these factors at the tumor scene. High MMP/TIMP expression by ECs from breast carcinomas, which may be consequence of the cross-talk between tumor cells and their surrounding microenvironment. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Tubular Carcinoma of the Breast: Advantages and Limitations of Breast Tomosynthesis

    PubMed Central

    Rocha, Ana; Reis, Alcinda

    2016-01-01

    Tubular carcinoma of the breast is a rare variant of invasive ductal carcinoma. We report a case of 42-year-old asymptomatic female with a histopathological proven multifocal tubular carcinoma, studied by mammography, Tomosynthesis, Ultrasound, and Magnetic Resonance. Herein, we discuss the advantages and limitations of Tomosynthesis, an emerging imaging technique, in this particular case. PMID:28116205

  4. Lugol's iodine identifies synchronous invasive carcinoma--time for a clinical trial.

    PubMed

    Kanatas, A N; Jenkins, G W; Sutton, D; McCaul, J A

    2011-07-01

    Lugol's iodine is currently under investigation as a technique to detect dysplasia, carcinoma in situ and invasive carcinoma at resection margins, plus further afield. Lugol's iodine is inexpensive and easy to use. We present two cases where the technique revealed abnormal mucosa (one carcinoma, one squamous cell carcinoma in situ) at distant sites from the tumour being treated within oral cavity and oropharynx.

  5. [Invasive micropapillary carcinoma of gallbladder: a clinicopathologic study].

    PubMed

    Yao, J G; Yin, M X; Wang, C H; Liu, Y

    2016-11-08

    Objective: To study the clinicopathologic features of invasive micropapillary carcinoma (IMPC) of the gallbladder. Methods: Among 160 resected cases of gallbladder adenocarcinomas, the clinical and histological features of gallbladder adenocarcinomas with invasive micropapillary components (IMPC≥5%) were studied. Results: The detection rate of IPMC among gallbladder adenocarcinomas was 19.4% (31/160). Among these 31 cases, the patients' age ranged from 42 to 84 years (mean 64.8 years). The male-to-female ratio was 1∶4.Histologically, 19 cases were characterized by small papillary tufts lacking central fibrovascular cores, lying freely within the clefts of fibrous tissue, resembling IMPC of the breast; in five cases, the micropapillary tufts floated within cystic spaces lined by tumor cells, resembling IMPC of the lung; in four cases, slender, delicate filiform processes on the tumor surface with classic IMPC in the depth of gallbladder was observed; and in three cases mixed features were seen. Small cluster invasion (SCI) was seen adjacent to the IMPC. The lymph node metastatic rate, the lymphovascular invasion rate, and the SCI detection rate were significantly higher in the IMPC group (P=0.000). The IMPC detection rate was related to poorer histological differentiation and increased T stage (P=0.012, C=0.67; P=0.011, C=0.68). The two-year survival rate of IMPC (4/18) was significantly lower than usual gallbladder carcinoma (54.8%, 23/42). Conclusions: Compared to conventional adenocarcinoma of the gallbladder, IMPC has a more advanced tumor status and is prone to lymphovascular invasion and lymph node metastasis, which thus leads to short-term survival. Moreover, SCI may play an important role in the invasion of the IMPC of the gallbladder.

  6. Tumor Microenvironment and Progression to Invasion after a Diagnosis of Ductal Carcinoma In Situ

    DTIC Science & Technology

    2013-03-01

    detected symptomatically were more likely to have a recurrence than cases detected by screening mammography (HR=1.6; 95% CI 0.9- 3.0). Tumor size, grade...of breast cancers were detected via mammography (85.4%). Use of tamoxifen was reported by 38.0% of women, most frequently among women undergoing

  7. Ultrasound-guided cryoablation of invasive ductal carcinoma inside the MR room.

    PubMed

    Tozaki, Mitsuhiro; Fukuma, Eisuke; Suzuki, Takako; Hoshi, Kazuei

    2010-01-01

    One disadvantage of ultrasound (US)-guided cryoablation of breast cancer is the difficulty in visualizing the area behind the ice ball because of acoustic shadowing. We performed US-guided cryoablation with the patient in prone position inside the MR room. The lumpectomy specimen after cryoablation revealed dense fibrosis without residual viable cancer cells. The combination of needle insertion under US guidance with planning and verification using magnetic resonance imaging may be a feasible and promising treatment protocol.

  8. Tumor Microenvironment and Progression to Invasion after a Diagnosis of Ductal Carcinoma In Situ

    DTIC Science & Technology

    2013-11-01

    Aspirin and Colorectal Cancer Incidence and Mortality by CTNNB1 Expression: A Molecular Pathological Epidemiology (MPE) Study Sun R, Nishihara R, Qian ZR...Chan AT, and Ogino S Purpose: Experimental studies showed that aspirin down-regulates theWNT/CTNNB1 (b-catenin) signaling ASPO 37th Annual Meeting

  9. Tumor Microenvironment and Progression to Invasion after a Diagnosis of Ductal Carcinoma In Situ

    DTIC Science & Technology

    2012-03-01

    received, ranging from 86.5% among cases receiving no further treatment after biopsy to 100% among women receiving a bilateral mastectomy . Women... mastectomy (94.7%). Tamoxifen use reduced the risk of a second event by about 20% among all treatment groups, with the exception of those undergoing...bilateral mastectomy . We have also examined tumor and patient characteristics in relation to DCIS disease-free survival in the WISC Cohort. DCIS cases

  10. Tumor Microenvironment and Progression to Invasion after a Diagnosis of Ductal Carcinoma In situ

    DTIC Science & Technology

    2012-03-01

    bilateral mastectomy . Women receiving breast conservation surgery followed by radiation had similar disease-free survival (95.4%) compared to women...undergoing ipsilateral mastectomy (94.7%). Tamoxifen use reduced the risk of a second event by about 20% among all treatment groups, with the...exception of those undergoing bilateral mastectomy . We have also examined tumor and patient characteristics in relation to DCIS disease-free survival in

  11. Effect of Hydrochloric Acid Decalcification on Expression Pattern of Prognostic Markers in Invasive Breast Carcinomas.

    PubMed

    Maclary, Shawn C; Mohanty, Sambit K; Bose, Shikha; Chung, Fai; Balzer, Bonnie L

    2017-02-01

    tumors comprised 11 grade 3 invasive ductal carcinomas, 2 grade 2 invasive ductal carcinomas, 2 grade 3 invasive lobular carcinoma, and 1 metastatic BC to bone. Nine cases showed Allred score 8 for ER, 1 case showed Allred score 4, 1 case showed Allred score 2, and the remaining 5 were ER negative. For PR, 1 showed Allred score 8, 2 Allred score 7, 4 Allred score 6, 1 each Allred score 5 and score 2 with the remainder negative for PR. Ki-67 ranged from 5% to 95%. Five cases showed p53 overexpression ranging from 35% to 95%. Five cases each showed 3+, 6 cases showed 2+ Her-2/neu, 3 cases showed 1+ Her-2/neu, and the remaining 2 were negative. All specimens demonstrated decline in ER, PR, Ki-67, and p53 immunoreactivity after 2 hours of decalcification, with additional decline up to 24 hours. The most significant declines in immunoreactivity occurred with Ki-67 and p53. Most of the Her-2/neu cases with an equivocal score declined to zero after 24 hours of decalcification. However, 3 out of 11 cases showing Her-2/neu overexpression remained at the baseline scoring even after extended (24 h) decalcification. Our results demonstrated that the decalcification process affects the immunoreactivity of the prognostic BC markers. There is progressive loss of reactivity at 2 hours and beyond for markers with lower degrees of expression. In addition, heterogeneity in marker distribution progressed from diffuse to more focal beyond 1 hour.

  12. Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

    PubMed

    Chikman, Bar; Davidson, Tima; Kais, Hasan; Jeroukhimov, Igor; Leshno, Ari; Sandbank, Judith; Halevy, Ariel; Lavy, Ron

    2016-01-01

    CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, <50 and ≥50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.

  13. Automatic Segmentation of Invasive Breast Carcinomas from DCE-MRI using Time Series Analysis

    PubMed Central

    Jayender, Jagadaeesan; Chikarmane, Sona; Jolesz, Ferenc A.; Gombos, Eva

    2013-01-01

    Purpose Quantitative segmentation methods based on black-box modeling and pharmacokinetic modeling are highly dependent on imaging pulse sequence, timing of bolus injection, arterial input function, imaging noise and fitting algorithms. To accurately segment invasive ductal carcinomas (IDCs) from dynamic contrast enhanced MRI (DCE-MRI) using time series analysis based on linear dynamic system (LDS) modeling. Methods We modeled the underlying dynamics of the tumor by a LDS and use the system parameters to segment the carcinoma on the DCE-MRI. Twenty-four patients with biopsy-proven IDCs were analyzed. The lesions segmented by the algorithm were compared with an expert radiologist’s segmentation and the output of a commercial software, CADstream. The results are quantified in terms of the accuracy and sensitivity of detecting the lesion and the amount of overlap, measured in terms of the Dice similarity coefficient (DSC). Results The segmentation algorithm detected the tumor with 90% accuracy and 100% sensitivity when compared to the radiologist’s segmentation and 82.1% accuracy and 100% sensitivity when compared to the CADstream output. The overlap of the algorithm output with the radiologist’s segmentation and CADstream output, computed in terms of the DSC was 0.77 and 0.72 respectively. The algorithm also shows robust stability to imaging noise. Simulated imaging noise with zero mean and standard deviation equal to 25% of the base signal intensity was added to the DCE-MRI series. The amount of overlap between the tumor maps generated by the LDS-based algorithm from the noisy and original DCE-MRI was DSC=0.95. Conclusion The time-series analysis based segmentation algorithm provides high accuracy and sensitivity in delineating the regions of enhanced perfusion corresponding to tumor from DCE-MRI. PMID:24115175

  14. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    PubMed Central

    Petridis, Christos; Brook, Mark N.; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C.; Hopper, John L.; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A.; Jud, Sebastian M.; Ekici, Arif B.; Beckmann, Matthias W.; Kerin, Michael J.; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Investigators, kConFab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J.; Sherman, Mark E.; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J.; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M.; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K.; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10−10; P-het for ILC vs IDC ER+ tumors = 1.8×10−4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there

  15. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    PubMed

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos; Brook, Mark N; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; Dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C; Hopper, John L; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A; Jud, Sebastian M; Ekici, Arif B; Beckmann, Matthias W; Kerin, Michael J; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Investigators, Kconfab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; McLean, Catriona A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline M; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J; Sherman, Mark E; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-04-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity

  16. Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion.

    PubMed

    Yan, Xia; Zhou, Huiling; Zhang, Tingting; Xu, Pan; Zhang, Shusen; Huang, Wei; Yang, Linlin; Gu, Xingxing; Ni, Runzhou; Zhang, Tianyi

    2015-12-01

    Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion.

  17. miR-367 promotes epithelial-to-mesenchymal transition and invasion of pancreatic ductal adenocarcinoma cells by targeting the Smad7-TGF-β signalling pathway

    PubMed Central

    Zhu, Z; Xu, Y; Zhao, J; Liu, Q; Feng, W; Fan, J; Wang, P

    2015-01-01

    Background: Aberrant Smad7 expression contributes to the invasion and metastasis of pancreatic cancer cells. However, the potential mechanism underlying aberrant Smad7 expression in human pancreatic ductal adenocarcinoma (PDAC) remains largely unknown. Methods: Bioinformatic prediction programmes and luciferase reporter assay were used to identify microRNAs regulating Smad7. The association between miR-367 expression and the overall survival of PDAC patients was evaluated by Kaplan–Meier analysis. The effects of miR-367 and Smad7 on the invasion and metastasis of pancreatic cancer cells were investigated both in vitro and in vivo. Results: We found that miR-367 downregulated Smad7 expression by directly targeting its 3′-UTR in human pancreatic cancer cells. High level of miR-367 expression correlated with poor prognosis of PDAC patients. Functional studies showed that miR-367 promoted pancreatic cancer invasion in vitro and metastasis in vivo through downregulating Smad7. In addition, we showed that miR-367 promoted epithelial-to-mesenchymal transition by increasing transforming growth factor-β (TGF-β)-induced transcriptional activity. Conclusions: The present study identified and characterised a signalling pathway, the miR-367/Smad7-TGF-β pathway, which is involved in the invasion and metastasis of pancreatic cancer cells. Our results suggest that miR-367 may be a promising therapeutic target for the treatment of human pancreatic cancer. PMID:25867271

  18. Snail promotes an invasive phenotype in lung carcinoma

    PubMed Central

    2012-01-01

    Background Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP). Methods To evaluate the functional importance of snail, a transciptional factor involved in EMT in lung tumors, we investigated its expression in a large set of lung carcinomas by immunohistochemistry. Expression of snail and effects of snail knockdown was studied in cell lines. Results Nuclear snail expression was seen in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There was significantly greater snail expression in SCLC compared to squamous cell or adenocarcinoma. Positive snail expression was associated with poor survival in the whole material and separately in squamous cell and adenocarcinomas. In Cox regression analysis, snail expression showed an independent prognostic value in all of these groups. In several cell lines knockdown of snail reduced invasion in both matrigel assay and in the myoma tissue model for invasion. The influence of snail knockdown on claudin expression was cell type specific. Snail knockdown in these cell lines modified the expression of MMP2 and MMP9 but did not influence the activation of these MMPs to any significant degree. Conclusions The results show that snail plays an important role in the invasive characteristics of lung carcinoma influencing the survival of the patients. Snail knockdown might thus be one option for targeted molecular therapy in lung cancer. Snail knockdown influenced the expression of claudins individually in a cell-line dependent manner but did not influence MMP expressions or activations to any significant degree. PMID:23157169

  19. Should histologic type be taken into account when considering neoadjuvant chemotherapy in breast carcinoma?

    PubMed

    Sullivan, Peggy S; Apple, Sophia K

    2009-01-01

    Neoadjuvant chemotherapy is becoming the standard of care in locally advanced breast cancers. With complete pathologic response, patients may have a better overall survival. However, most patients do not have a complete pathologic response, and it is unclear how this impacts survival and whether histologic subtype or chemotherapeutic histologic changes play a role. We retrospectively identified 49 cases of invasive breast carcinoma treated with neoadjuvant chemotherapy (40 ductal, nine lobular) and examined histologic and biologic features of ductal and lobular carcinoma before and after chemotherapy. Patients with lobular carcinomas presented at a later age and had lower grade tumors that were more likely estrogen and progesterone receptor positive. Ductal carcinomas had a greater frequency of HER-2/neu amplification and increased Ki-67 rate. After chemotherapy, none of the lobular carcinomas had complete pathologic response compared with 28% of the ductal carcinomas (p = 0.01). Lobular carcinomas had more lymph node metastases. At the time of clinical follow-up, no lobular carcinomas had evidence of disease. Only one lobular carcinoma case had any histologic changes after chemotherapy compared with 37-68% of ductal carcinomas (p < 0.05). In ductal carcinomas, higher grade and negative estrogen receptor expression before chemotherapy and presence of foam cell clusters, HER-2/neu expression, and absence of lymphatic or vascular space invasion after chemotherapy correlated with pathologic response (p < 0.05). Decreased Ki-67 rate after chemotherapy correlated with survival (p = 0.024). Breast biomarker status changed in 9% of all lobular carcinomas and 19% of all ductal carcinomas. Lobular carcinomas respond poorly to neoadjuvant chemotherapy as evidence by lack of complete pathologic response and rare histologic tissue response.

  20. Invasion patterns in stage I endometrioid and mucinous ovarian carcinomas: a clinicopathologic analysis emphasizing favorable outcomes in carcinomas without destructive stromal invasion and the occasional malignant course of carcinomas with limited destructive stromal invasion.

    PubMed

    Chen, Shirley; Leitao, Mario M; Tornos, Carmen; Soslow, Robert A

    2005-07-01

    Stage I, low-grade endometrioid and mucinous ovarian carcinomas have an excellent prognosis. Published data have suggested that destructive stromal invasion, a relatively uncommon finding in these tumors, is a poor prognostic factor. We investigated this by studying all FIGO stage I, grades 1 and 2 (of 3) endometrioid and mucinous ovarian carcinomas that were surgically staged at the Memorial Sloan-Kettering Cancer Center from 1980 to 2000. We undertook a careful review of all available slides using current diagnostic criteria and correlated histopathologic indices with clinical outcome data. Cases studied included 13 endometrioid ovarian carcinomas (stage IA, eight; stage IC, five) and six intestinal mucinous ovarian carcinomas (stage IA, three; stage IC, three). All of the tumors contained areas of expansile invasion, greater than that acceptable for microinvasion, and were thus diagnosed as carcinomas instead of borderline tumors. Nevertheless, nearly all demonstrated borderline tumor (noninvasive) components. Six tumors contained at least one focus of destructive stromal invasion (two endometrioid and four mucinous ovarian carcinomas). Four additional cases showed a focus suspicious for but not diagnostic of destructive invasion ('indeterminate for destructive invasion') (two endometrioid and two mucinous ovarian carcinomas). Follow-up data were available for 17 patients. The median follow-up was 81 months (range, 9-161 months). In all, 14 patients were alive with no evidence of disease (expansile invasion alone, eight; destructive stromal invasion, four; and indeterminate for destructive invasion, two). Three patients died of their disease (destructive stromal invasion, two; and indeterminate for destructive invasion, one). The size, number, and nuclear grade of destructive stromal invasion foci did not appear to have an impact on survival in this relatively limited number of patients. Outcome data in patients with stage I, low-grade endometrioid and mucinous

  1. Expression of metalloproteases and their inhibitors by tumor and stromal cells in ductal carcinoma in situ of the breast and their relationship with microinvasive events.

    PubMed

    González, L O; González-Reyes, S; Junquera, S; Marín, L; González, L; Del Casar, J M; González, J M; Vizoso, Francisco

    2010-09-01

    This study aimed to investigate the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ (DCIS). We used inmunohistochemistry to compare the expression of MMPs and TIMPs in tumor or stromal cells for 50 pure DCIS and 12 DCIS with microinvasive foci. Score values for collagenase-1 (MMP-1), membrane type 1 MMP (MMP-14), and TIMP-1, were significantly higher in pure DCIS than in DCIS with microinvasive foci, whereas stromalysin-3 (MMP-11) expression was significantly higher in DCIS with microinvasive foci. Both fibroblasts and mononuclear inflammatory cells (MICs) surrounding pure DCIS showed more frequently expression of MMP-1, MMP-14, and TIMP-3, whereas MMP-11 expression was more frequent in MICs of microinvasive tumors. MICs of microinvasive foci more frequently showed the expression of gelatinase A (MMP-2), MMP-11, collagenase-3 (MMP-13), and TIMP-1, than MICs surrounding pure DCIS; whereas peri-ductal MICs and fibroblasts from pure DCIS expressed TIMP-3 more commonly than these cells at microinvasive foci. There are significant differences in the expression of MMPs and TIMPs, so in tumor cells and stromal cells, between pure DCIS and DCIS with microinvasive foci. Therefore, these staining patterns might display potential applications as biological markers, such as in evaluating microinvasion in resection specimens of breast tumors.

  2. Long-Term Outcome in Patients With Ductal Carcinoma In Situ Treated With Breast-Conserving Therapy: Implications for Optimal Follow-up Strategies

    SciTech Connect

    Shaitelman, Simona F.; Wilkinson, J. Ben; Kestin, Larry L.; Ye Hong; Goldstein, Neal S.; Martinez, Alvaro A.; Vicini, Frank A.

    2012-07-01

    Purpose: To determine 20-year rates of local control and outcome-associated factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy (BCT). Methods and Materials: All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. Results: One hundred forty-five cases were evaluated; the median follow-up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after diagnosis. Young age and cancerization of lobules predicted for IBTR at <10 years, and increased slide involvement and atypical ductal hyperplasia were associated with IBTR at later time points. Conclusions: Patients with DCIS treated with BCT have excellent long-term rates of local control. Predictors of IBTR vary over time, and the risk of recurrence seems highest within 10 to 12 years after diagnosis.

  3. Minimally invasive image-guided therapies for hepatocellular carcinoma

    PubMed Central

    Abdelsalam, Mohamed E; Murthy, Ravi; Avritscher, Rony; Mahvash, Armeen; Wallace, Michael J; Kaseb, Ahmed O; Odisio, Bruno C

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic liver disease, which affects management decisions. Image-guided percutaneous ablative or transarterial therapies have acquired wide acceptance in HCC management as a single treatment modality or combined with other treatment options in patients who are not amenable for surgery. Recently, such treatment modalities have also been used for bridging or downsizing before definitive treatment (ie, surgical resection or liver transplantation). This review focuses on the use of minimally invasive image-guided locoregional therapies for HCC. Additionally, it highlights recent advancements in imaging and catheter technology, embolic materials, chemotherapeutic agents, and delivery techniques; all lead to improved patient outcomes, thereby increasing the interest in these invasive techniques. PMID:27785450

  4. Apocrine carcinoma arising in a complex fibroadenoma: a case report.

    PubMed

    Mele, Marco; Vahl, Pernille; Funder, Jonas Amstrup; Sorensen, Anne Schmidt; Jensen, Vibeke

    2014-01-01

    A carcinoma arising in a fibroadenoma is a rare event, which often entails a diagnostic challenge. The most common type is the lobular carcinoma and secondary a ductal carcinoma. We present an extremely rare case of malignant development of an invasive apocrine carcinoma in a complex fibroadenoma and underline the importance for clinicians to recognize the possibility of benign and malignant co-existence especially in older women.

  5. The relationship between total and phosphorylated STAT1 and STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer

    PubMed Central

    Gujam, Fadia J.A.; McMillan, Donald C.; Edwards, Joanne

    2016-01-01

    The aim of the present study was to examine the relationship between tumour cell expression of total and phosphorylated STAT1 (ph-STAT1) and STAT3 (ph-STAT-3), components of tumour microenvironment and survival in patients with invasive ductal breast cancer. Immunohistochemical analysis of total and ph-STAT1, and STAT3 were performed on tissue microarray of 384 breast cancer specimens. Tumour cell expression of STAT1 and STAT3 at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression. These results were related to cancer specific survival (CSS) and phenotypic features of the tumour and the host. High ph-STAT1 and ph-STAT3 tumour cell expression were associated with increased ER (both P≤0.001) and PR (both P <0.05), reduced tumour grade (P=0.015 and P<0.001 respectively) and necrosis (both P=0.001). Ph-STAT1 was associated with increased general inflammatory infiltrate (P=0.007) and ph-STAT3 was associated with lower CD4+ infiltration (P=0.024). In multivariate survival analysis, only high ph-STAT3 tumour cell expression was a predictor of improved CSS (P=0.010) independent of other tumour and host-based factors. STAT1 and STAT3 tumour cell expression appeared to be an important determinant of favourable outcome in patients with invasive ductal breast cancer. The present results suggest that STAT1 and STAT3 may affect disease outcome through direct impact on tumour cells, counteracting aggressive tumour features, as well as interaction with the surrounding microenvironment. PMID:27769057

  6. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

    NASA Technical Reports Server (NTRS)

    Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

    2003-01-01

    Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

  7. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

    NASA Technical Reports Server (NTRS)

    Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

    2003-01-01

    Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

  8. Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression.

    PubMed

    Malekian, Negin; Habibi, Jafar; Zangooei, Mohammad Hossein; Aghakhani, Hojjat

    2016-11-01

    There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test. The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis. In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. A validation study of quantum dot multispectral imaging to evaluate hormone receptor status in ductal carcinoma in situ of the breast.

    PubMed

    Yu, Jing; Monaco, Sara E; Onisko, Agnieszka; Bhargava, Rohit; Dabbs, David J; Cieply, Kathleen M; Fine, Jeffrey L

    2013-03-01

    The assessment of hormone receptors, including estrogen receptor and progesterone receptor, has become a standard practice in breast cancer management. However, the need for multiple sections to evaluate each receptor individually by conventional immunohistochemistry may preclude the analysis on some core biopsies with a limited amount of tumors. The aim of the study was to validate the quantitative analysis of nuclear markers estrogen receptor and progesterone receptor by quantum dot-based immunohistochemistry using a multispectral imaging system in ductal carcinoma in situ of the breast. Consecutive sections from a total of 17 cases of ductal carcinoma in situ with excisional biopsies or mastectomies were stained with conventional immunohistochemistry and quantum dot-based, single- and double-labeled immunohistochemistry for estrogen receptor and progesterone receptor. The semiquantitative results from double-labeled, quantum dot-based immunohistochemistry were compared with those from single-labeled, quantum dot-based immunohistochemistry as well as from conventional immunohistochemistry. There was good concordance between double- and single-labeled quantum dot-based immunohistochemistry, and quantum dot-based immunohistochemistry correlated well with conventional immunohistochemistry (Spearman correlation coefficient range from 0.884 to 0.958, P < .001). The findings proved the validity and accuracy of quantum dot-based multiplex, multispectral technique in detecting 2 tumor markers in the same cellular compartment simultaneously on a single slide. This technique may enhance our ability to assess multiple breast tumor markers in specimens with limited available tissue. However, several technical and logistic issues await significant improvement before this novel technique can be justified for routine clinical application. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis.

    PubMed

    Kanematsu, Miyuki; Morimoto, Masami; Takahashi, Masako; Honda, Junko; Bando, Yoshimi; Moriya, Takuya; Tadokoro, Yukiko; Nakagawa, Misako; Takechi, Hirokazu; Yoshida, Takahiro; Toba, Hiroaki; Yoshida, Mitsuteru; Kajikawa, Aiichiro; Tangoku, Akira; Imoto, Issei; Sasa, Mitsunori

    2016-01-01

    Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.

  11. Anti-proliferative role of recombinant lethal toxin of Bacillus anthracis on primary mammary ductal carcinoma cells revealing its therapeutic potential.

    PubMed

    Khandia, Rekha; Pattnaik, Bramhadev; Rajukumar, Katherukamem; Pateriya, Atul; Bhatia, Sandeep; Murugkar, Harshad; Prakash, Anil; Pradhan, Hare Krishna; Dhama, Kuldeep; Munjal, Ashok; Joshi, Sunil K

    2017-05-30

    Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p < 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ± 1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = -773.96), followed by nerve growth factor receptor (NGFR) and human epidermal growth factor receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic molecule against primary mammary ductal carcinoma cells and also the c-Met as potential alternative receptor for LF to mediate and modulate PA independent signal transduction.

  12. Correlations among p53, Her-2/neu, and ras overexpression and aneuploidy by multiparameter flow cytometry in human breast cancer: evidence for a common phenotypic evolutionary pattern in infiltrating ductal carcinomas.

    PubMed

    Smith, C A; Pollice, A A; Gu, L P; Brown, K A; Singh, S G; Janocko, L E; Johnson, R; Julian, T; Hyams, D; Wolmark, N; Sweeney, L; Silverman, J F; Shackney, S E

    2000-01-01

    Human solid tumors develop multiple genetic abnormalities that accumulate progressively in individual cells during the course of tumor evolution. We sought to determine whether there are specific sequences of occurrence of these progressive evolutionary changes in human breast cancers by performing correlated cell-by-cell measurements of cell DNA content, p53 protein, Her-2/neu protein, and ras protein by multiparameter flow cytometry in 56 primary tumor samples obtained at surgery. In addition, p53 allelic loss and Her-2/neu gene amplification were determined by fluorescence in situ hybridization in cells from the same samples. We reasoned that if there is a specific order in which genetic changes occur, the same early changes would be found consistently in the cells with the fewest abnormalities. We reasoned further that late-developing abnormalities would not occur alone in individual cells but would almost always be found together with the early changes inherited by the same cells. By these criteria, abnormalities involving p53 generally occurred early in the course of development of invasive breast cancers, whereas ras protein overexpression was found to be a late-occurring phenomenon. Within individual tumors, cellular p53 overexpression was often observed alone in individual cells, whereas ras protein overexpression was rarely observed in the absence of p53 overexpression and/or Her-2/neu overexpression in the same cells. Furthermore, the intracellular level of each abnormally expressed protein was found to increase progressively as new abnormalities were acquired. Infiltrating ductal carcinomas exhibited characteristic phenotypic patterns in which p53 allelic loss and/or p53 protein overexpression, Her-2/neu amplification and/or overexpression, aneuploidy, and ras overexpression accumulated within individual cells. However, this pattern was not a prominent feature of lobular breast cancers. All six lobular breast cancers studied were diploid. p53 allelic

  13. Vasculogenic mimicry in hepatocellular carcinoma contributes to portal vein invasion

    PubMed Central

    Zhisheng, Zhang; Lin, Cui; Yayun, Qian; Feng, Jin; Hao, Gu; Shintaro, Ishikawa; Hisamitsu, Tadashi; Shiyu, Guo; Yanqing, Liu

    2016-01-01

    Portal vein invasion (PVI) is common in hepatocellular carcinoma (HCC) and largely contributes to tumor recurrence after radical tumor resection or liver transplantation. Vasculogenic mimicry (VM) was an independent vascular system lined with tumor cells and associated with poor prognosis of HCC. The present study was conducted to evaluate the relationship between VM and portal vein invasion. A total of 44 HCC cases receiving anatomic liver resection were included in the study and were divided into groups with and without PVI. The prevalence of VM in each group was examined by CD34-PAS dual staining. The regulatory molecules of VM formation such as Notch1, Vimentin and matrix metalloproteinases (MMPs) were investigated by immunohistochemical staining. Analysis was performed to explore the association of PVI, VM and the VM regulatory molecules. PVI was found in 40.91% (18/44) cases and VM was found in 38.64% (17/44) cases in total samples. The incidence of VM was 72.22% (13/18) in PVI group while it was 15.38% (4/26) in non-PVI group (P<0.001), VM formation was positively correlated with PVI (r=0.574, P<0.001). The VM forming regulatory molecules such as Notch1, Vimentin, MMP-2 and MMP-9 were found to be correlated with PVI in HCC patients. Taken together, our results suggested that VM formation, alone with its regulatory molecules, is the promoting factor of PVI in hepatocellular carcinoma. PMID:27793002

  14. Vasculogenic mimicry in hepatocellular carcinoma contributes to portal vein invasion.

    PubMed

    Jue, Chen; Zhifeng, Wu; Zhisheng, Zhang; Lin, Cui; Yayun, Qian; Feng, Jin; Hao, Gu; Shintaro, Ishikawa; Hisamitsu, Tadashi; Shiyu, Guo; Yanqing, Liu

    2016-11-22

    Portal vein invasion (PVI) is common in hepatocellular carcinoma (HCC) and largely contributes to tumor recurrence after radical tumor resection or liver transplantation. Vasculogenic mimicry (VM) was an independent vascular system lined with tumor cells and associated with poor prognosis of HCC. The present study was conducted to evaluate the relationship between VM and portal vein invasion. A total of 44 HCC cases receiving anatomic liver resection were included in the study and were divided into groups with and without PVI. The prevalence of VM in each group was examined by CD34-PAS dual staining. The regulatory molecules of VM formation such as Notch1, Vimentin and matrix metalloproteinases (MMPs) were investigated by immunohistochemical staining. Analysis was performed to explore the association of PVI, VM and the VM regulatory molecules. PVI was found in 40.91% (18/44) cases and VM was found in 38.64% (17/44) cases in total samples. The incidence of VM was 72.22% (13/18) in PVI group while it was 15.38% (4/26) in non-PVI group (P<0.001), VM formation was positively correlated with PVI (r=0.574, P<0.001). The VM forming regulatory molecules such as Notch1, Vimentin, MMP-2 and MMP-9 were found to be correlated with PVI in HCC patients. Taken together, our results suggested that VM formation, alone with its regulatory molecules, is the promoting factor of PVI in hepatocellular carcinoma.

  15. Immunohistochemical staining patterns of tenascin in invasive breast carcinomas.

    PubMed

    Shoji, T; Kamiya, T; Tsubura, A; Hatano, T; Sakakura, T; Yamamoto, M; Morii, S

    1992-01-01

    Eighty-two cases of primary invasive breast carcinoma and adjacent "normal" mammary glands were examined immunohistochemically for tenascin expression and distribution. Formalin-fixed tissues pretreated with actinase were processed by the avidin-biotin complex method using anti-human tenascin monoclonal antibody (RBC1). In normal mammary glands, tenascin was distributed around the ducts and ductules but not around the acini. In carcinomas, a high incidence of tenascin-positive cases (greater than 67%) was seen with various histological appearances, with the exception of lobular carcinoma where a low incidence was found (25%). Although intense staining was seen around cancerous foci when compared with normal mammary glands, tenascin was often expressed at cancer-mesenchymal junctions with dense fibrotic stroma, but not at junctions with active inflammatory change and a loose fibrotic stroma. Tenascin, expression is not an all-or-none marker for mammary malignancy and the staining pattern suggests either a role in stimulating cancer cells or a host defence mechanism accompanied by a desmoplastic response to them.

  16. The invasive lobular carcinoma as a prototype luminal A breast cancer: A retrospective cohort study

    PubMed Central

    2010-01-01

    Background Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known. Methods We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC). Results The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07). Conclusions ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC. PMID:21126378

  17. Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

    SciTech Connect

    Vargas, Carlos; Kestin, Larry; Go, Nel; Krauss, Daniel; Chen, Peter; Goldstein, Neal; Martinez, Alvaro; Vicini, Frank A. . E-mail: fvicini@beaumont.edu

    2005-12-01

    Purpose: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. Materials and Methods: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). Results: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy {<=}9 MeV (p = 0.03, HR 1.41), final margins {<=}2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. Conclusions: After treatment for DCIS, 10-year rates of local control

  18. Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: a pilot study.

    PubMed

    Çiriş, Ibrahim Metin; Bozkurt, Kemal Kürşat; Başpinar, Sirin; Kapucuoğlu, Fatma Nilgün

    2011-03-15

    Cyclooxygenase-2 (COX-2) is a prostaglandin synthase that catalyzes the synthesis of prostaglandin G2 and H2. It has been shown that COX-2 plays an important role in tumorigenesis of different tumor types and it is thought to take part in breast carcinogenesis. In the present study, we aimed to investigate the relationship of immunohistochemical COX-2 expression with clinicopathological parameters, including HER-2/neu overexpression in invasive breast carcinoma (IBC). Our study population comprised 10 normal breasts, 25 ductal carcinomas in situ (DCIS), and 51 invasive breast carcinomas. Immunohistochemical overexpressions of COX-2 and HER-2/neu were investigated in sections of formalin-fixed, paraffin-embedded blocks by 3 observers. In normal breast, DCIS and IBC, the COX-2 overexpression rate was 0%, 84%, and 58.8%, respectively. In IBC, COX-2 overexpression had a significant relationship with HER-2/neu overexpression (p=0.026) and a high histological grade (p=0.026). COX-2 expression in both DCIS (n=25) and IBC (n=51) was significantly higher than in normal breast tissue (p<0.0001). In addition, the COX-2 expression rate was significantly higher in DCIS than in IBC (p=0.042). Our results indicated that COX-2 overexpression correlates with aggressive phenotypic features, such as HER-2/neu overexpression and high histological grade in IBC. Increased expression of COX-2 in both DCIS and IBC in comparison to normal breast could indicate a role in breast carcinogenesis. COX-2 overexpression may provide a clinically useful biomarker for estimating tumor aggressiveness.