WorldWideScience

Sample records for breast carcinoma triple

  1. Vascular characterisation of triple negative breast carcinomas using dynamic MRI

    Energy Technology Data Exchange (ETDEWEB)

    Li, Sonia P.; Beresford, Mark J.; Ah-See, Mei-Lin W.; Makris, Andreas [Mount Vernon Cancer Centre, Academic Oncology Unit, Northwood, Middlesex (United Kingdom); Padhani, Anwar R.; Taylor, N.J.; Stirling, J.J. [Mount Vernon Hospital, Paul Strickland Scanner Centre, Northwood, Middlesex (United Kingdom); D' Arcy, James A.; Collins, David J. [Royal Marsden NHS Foundation Trust and Institute of Cancer Research, CR UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom)

    2011-07-15

    Triple-negative (ER-/PR-/HER2-) breast carcinomas (TNBC) are aggressive tumours with underexplored imaging features. This study investigates whether their vascular characteristics as assessed by dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast-enhanced (DSC) MRI are distinct from the prognostically more favourable ER+/PR+/HER2- cancers. Patients with primary breast cancer underwent MRI before neoadjuvant chemotherapy and were identified as ER-/PR-/HER2- or ER+/PR+/HER2- from core biopsy specimens. MRI parameters reflecting tissue perfusion, permeability, and extracellular leakage space were measured. Values for inflow transfer constant (K{sup trans}), outflow rate constant (k{sub ep}), leakage space (v{sub e}), area under the gadolinium curve (IAUGC{sub 60}), relative blood volume (rBV) and flow (rBF), and Mean Transit Time (MTT) were compared across receptor status and with known prognostic variables. Thirty seven patients were assessable in total (16 ER-/PR-/HER2-, 21 ER+/PR+/HER2-). Lower v{sub e} (p = 0.001), shorter MTT (p = 0.007) and higher k{sub ep} values (p = 0.044) were observed in TNBC. v{sub e} was lower across all T stages, node-negative (p = 0.004) and low-grade TNBC (p = 0.037). v{sub e} was the best predictor of triple negativity (ROC AUC 0.80). TNBC possess characteristic features on imaging, with lower extracellular space (higher cell density) and higher contrast agent wash-out rate (higher vascular permeability) suggesting a distinctive phenotype detectable by MRI. (orig.)

  2. Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

    Science.gov (United States)

    Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki

    2014-03-01

    We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed.

  3. Triple negative invasive lobular carcinoma of the breast presents as small bowel obstruction

    Directory of Open Access Journals (Sweden)

    Mariya Khokhlova

    2017-01-01

    Full Text Available Metastasis from breast carcinoma to the gastrointestinal tract (GIT is very uncommon. To date, only a few cases have been described worldwide. Of those which do metastasize to the GIT, only estrogen receptor (ER, progesterone receptor (PR and HER2-neu receptor positive cancers have been reported and none have been mentioned in the U.S. We report a case of a 70-year-old white female with history of triple negative lobular carcinoma eight years earlier who presented with solitary jejunal mass causing obstruction.

  4. Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

    Science.gov (United States)

    2017-08-28

    Breast Carcinoma Metastatic in the Bone; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  5. Clinicopathological significance and prognostic value of CD133 expression in triple-negative breast carcinoma.

    Science.gov (United States)

    Zhao, Po; Lu, Yali; Jiang, Xuege; Li, Xiaoying

    2011-05-01

    Currently, CD133 is one of the best markers to characterize cancer stem cells and Her-1 is reported as an important marker for the prognosis of triple-negative breast cancer. To investigate the relationship between the expression of CD133 and Her-1 and clinicopathology as well as prognosis in triple-negative breast cancer, 67 cases of triple-negative invasive ductal breast carcinoma taken from 422 patients with breast cancer were analyzed by immunohistochemistry and clinicopathology with follow-up. The CD133 and Her-1 were expressed as positive in 43.3% (29/67) and 53.7% (36/67) of patients, respectively. The expression of CD133 corresponded to tumor size (P = 0.022), clinical stage (P = 0.001) and lymphatic metastasis (P = 0.001), but not to age and histological grade. By Kaplan-Meier analysis the expression of CD133 was correlative with overall survival (OS) (log rank = 9.346, P = 0.002) and disease free survival (DFS) (log rank = 38.840, P = 0.0001) time of breast cancer patients. The expression of Her-1 was corresponding to tumor size (P = 0.031), clinical stage (P = 0.005) and lymphatic metastasis (P = 0.002), but not to age and histological grade. By Kaplan-Meier analysis the expression of Her-1 was correlative with overall survival (OS) (log rank = 7.998, P = 0.005) and DFS (log rank = 4.227, P = 0.040) time of patients with cancer. It is concluded that the expression of CD133 and Her-1 may be correlative with prognosis in triple-negative breast cancer. © 2011 Japanese Cancer Association.

  6. Histological analysis of gamma delta T lymphocytes infiltrating human triple-negative breast carcinomas

    Directory of Open Access Journals (Sweden)

    Jose Villacorta Hidalgo

    2014-12-01

    Full Text Available Breast cancer is the leading cause of cancer death in women and the second most common cancer worldwide after lung cancer. The remarkable heterogeneity of breast cancers influences numerous diagnostic, therapeutic and prognostic factors. Triple-negative breast cancers (TNBCs lack expression of HER2 and the estrogen and progesterone receptors and often contain lymphocytic infiltrates. Most of TNBCs are invasive ductal carcinomas (IDCs with poor prognosis, whereas prognostically more favorable subtypes such as medullary breast carcinomas (MBCs are somewhat less frequent. Infiltrating T cells have been associated with an improved clinical outcome in TNBCs. The prognostic role of γδ T cells within CD3+ tumor-infiltrating T lymphocytes remains unclear. We analyzed 26 TNBCs, 14 IDCs and 12 MBCs, using immunohistochemistry for the quantity and patterns of γδ T-cell infitrates within the tumor microenvironment. In both types of TNBCs, we found higher numbers of γδ T cells in comparison with normal breast tissues and fibroadenomas. The numbers of infiltrating γδ T cells were higher in MBCs than in IDCs. γδ T cells in MBCs were frequently located in direct contact with tumor cells, within the tumor and at its invasive border. In contrast, most γδ T cells in IDCs were found in clusters within the tumor stroma. These findings could be associated with the fact that the patient’s prognosis in MBCs is better than that in IDCs. Further studies to characterize these γδ T cells at the molecular and functional level are in progress.

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

    Science.gov (United States)

    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.

  8. GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

    Science.gov (United States)

    2017-05-22

    Estrogen Receptor Negative Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Triple Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  9. Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer.

    Science.gov (United States)

    Caliari, Diego; Zappulli, Valentina; Rasotto, Roberta; Cardazzo, Barbara; Frassineti, Federica; Goldschmidt, Michael H; Castagnaro, Massimo

    2014-09-25

    Human breast cancer is a heterogeneous disease classified by molecular subtyping into luminal A, luminal B, HER2-overexpressing, basal-like, claudin-low and normal-breast like. The routinely applied and standardized immunohistochemical-based surrogates of this classification group together the last three entities as triple-negative breast cancer (TNBCs) that show the most diverse and complex heterogeneity and represent a therapeutic challenge. In the present work 156 feline mammary lesions consisting of feline mammary carcinomas (FMCs), benign neoplasms, and hyperplastic/dysplastic tissues were evaluated histologically and by immunohistochemistry for expression of basal and luminal cytokeratins (CK), vimentin, alpha-smooth muscle actin, calponin, estrogen receptor (ER) alpha (a), and progesterone receptor (PR). Thirty-seven FMCs with 27 matched non-neoplastic controls were also investigated for gene expression of ERa, ER beta, PR, and HER2. A large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs + tumors, that showed bilineage (luminal and myoepithelial) differentiation. Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor. These results indicate and potentially explain the high incidence of triple-negative, vimentin + aggressive tumors in cats that may used to elucidate some of the challenging features of TNBCs in women.

  10. Triple-negative breast carcinoma: heterogeneity in immunophenotypes and pharmacokinetic behavior.

    Science.gov (United States)

    Vilagran Fraguell, M; Sentís Crivillé, M; del Riego Ferrari, J; Andreu Navarro, F J; Dalmau Portulàs, E; Planas Roquerols, J; Lluïsa Baré, M

    2016-01-01

    To evaluate the morphokinetic, pharmacokinetic, and diffusion characteristics of triple-negative breast cancers on magnetic resonance (MR) imaging and to analyze whether there is a relation between these parameters and the time to progression. This was a retrospective observational study of a consecutive series of 100 patients with histologically confirmed triple-negative breast cancer studied at our center between January 2005 and December 2010. We reviewed the findings on MR locoregional extension studies, the histological findings, and the follow-up of patients until August 2014. The most common MR findings for these tumors were a rounded mass (47.3%), well-defined borders (53.7%), ring enhancement (46.2%), type 3 curves (50.5%), hyperintensity within the tumor on T2-weighted sequences, high ADC values (1.04 × 10(-3) mm2/s), and increased capillary permeability (Kep) (0.94 min(-1)). No significant association was observed between the morphokinetic or pharmacokinetic characteristics and the time to progression. The in situ component in the surgical specimens was high, although its expression was low. During follow-up, 25% of patients had metastases, with a predilection for the visceral organs, and survival was low. Tumors with the triple-negative phenotype mostly presented in MR as rounded tumors with well-defined borders and ring enhancement. We found no significant association between the morphokinetic or pharmacokinetic characteristics and the time to progression. Copyright © 2015. Published by Elsevier España, S.L.U.

  11. Oxidative stress and counteracting mechanisms in hormone receptor positive, triple-negative and basal-like breast carcinomas

    Directory of Open Access Journals (Sweden)

    Soini Ylermi

    2011-06-01

    Full Text Available Abstract Background Triple-negative breast cancer (TNBC and basal-like breast cancer (BLBC are breast cancer subtypes with an especially poor prognosis. 8-Hydroxydeoxyguanosine (8-OHdG is a widely used marker of oxidative stress and the redox-state-regulating enzymes peroxiredoxins (PRDXs are efficient at depressing excessive reactive oxygen species. NF-E2-related factor 2 (Nrf2 and Kelch-like ECH-associated protein 1 (Keap1 are redox-sensitive transcription factors that regulate PRDX expression. This is the first study to assess oxidative stress and or cell redox state-regulating enzymes in TNBC and BLBC. Methods We assessed immunohistochemical expression of 8-OHdG, Nrf2, Keap1, PRDX III and PRDX IV in 79 women with invasive ductal breast carcinomas. Of these tumors, 37 represented TNBC (grade II-III tumors with total lack of ER, PR and human epidermal growth factor receptor 2 [HER2] expression. Control cases (n = 42 were ER-positive, PR-positive and HER2-negative. Of the 37 TNBCs, 31 had BLBC phenotype (TNBC with expression of cytokeratin 5/6 or epidermal growth factor receptor 1. Results Patients with TNBC had worse breast cancer-specific survival (BCSS than the control group (p = 0.015. Expression of 8-OHdG was significantly lower in TNBC than in the non-TNBC group (p vs. the non-TNBC group (p = 0.022. Conclusions Cellular redox state markers may be promising targets when elucidating the pathogenesis of TNBC.

  12. Prognostic value of androgen receptor expression in triple negative breast carcinomas: personal experience and comments on a review about “Triple-negative breast cancer: treatment challenges and solutions” by Collignon et al

    Directory of Open Access Journals (Sweden)

    Ieni A

    2016-08-01

    Full Text Available Antonio Ieni,1 Valeria Barresi,1 Giuseppina Rosaria Rita Ricciardi,2 Barbara Adamo,3 Vincenzo Adamo,2 Giovanni Tuccari11Department of Human Pathology of Adult and Evolutive Age “Gaetano Barresi”, Section of Pathology, University of Messina, AOU “Policlinico G Martino”; 2Medical Oncology Unit AOOR Papardo-Piemonte, Department of Human Pathology of Adult And Evolutive Age “Gaetano Barresi”, University of Messina, Messina, Italy; 3Medical Oncology Hospital Clinic, Barcelona, SpainRecently, we read with great interest the review by Collignon et al entitled “Triplenegative breast cancer: treatment challenges and solutions”,1 which appeared in the last issue of Breast Cancer: Targets and Therapy. In this article, the authors extensively reviewed studies concerning the opportunity to identify triple negative breast carcinoma (TNBC subtypes by newly proposed markers, taking into account their biological heterogeneity on the light of clinical implications.View original paper by Collignon et al.

  13. P16 but not retinoblastoma expression is related to clinical outcome in no-special-type triple-negative breast carcinomas.

    Science.gov (United States)

    Bogina, Giuseppe S; Lunardi, Gianluigi; Marcolini, Lisa; Brunelli, Matteo; Bortesi, Laura; Marconi, Marcella; Coati, Francesca; Valerio, Matteo; Guerriero, Massimo; Massocco, Alberto; Pegoraro, Maria C; Zamboni, Giuseppe

    2014-02-01

    Triple-negative breast carcinomas represent a tumor group of pivotal clinical importance given the lack of target therapies. The prognostic significance of triple-negative breast carcinomas remains unclear because of their histological and molecular heterogeneity. Currently, neither prognostic nor predictive factors are available for these tumors. Retinoblastoma (Rb) pathway loss has been linked to clinical outcome in various cancer types, including breast cancer. We investigated the association between Rb and p16 protein expression and clinical outcome in no-special-type triple-negative breast carcinomas. Immunohistochemical staining for Rb, p16, p53 and CK5 was carried out on a section from archival specimens of 117 no-special-type triple-negative breast carcinomas. Immunopositive p16 (p16+) and immunonegative Rb (Rb-) staining were seen in 49.5% and in 24.8% of tumors, respectively. There was an inverse correlation between p16+ and Rb- (PP16+ was correlated with G3 grade (PP=0.03), p53 overexpression (PP=0.01). Rb- was not associated with any clinicopathologic variable. Follow-up and therapy data were available in 95 patients. In 20 patients treated with surgery only, neither p16+ nor Rb- immunostaining were associated with disease-free survival and overall survival. In 75 patients treated with adjuvant chemotherapy, p16+ was associated with good response to therapy with significant increased disease-free survival (P=0.001) and showed a trend towards a statistical significance for increased overall survival (P=0.056); Rb- were not associated with disease-free survival and overall survival. In multivariate analysis, p16+ was independently associated with disease-free and overall survival, with a hazard ratio of 0.18 (95% CI: 0.06-0.51; P=0.001) and 0.21 (95% CI: 0.06-0.74; P=0.015), respectively. In patients with no-special-type triple-negative breast carcinomas, p16+ is related to good response to adjuvant chemotherapy and can be considered the best surrogate

  14. Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

    Science.gov (United States)

    Geredeli, Caglayan; Dogru, Osman; Omeroglu, Ethem; Yilmaz, Farise; Cicekci, Faruk

    2015-05-05

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases.

  15. Epidermal growth factor receptor expression in triple negative and nontriple negative breast carcinomas

    Directory of Open Access Journals (Sweden)

    Arathi A Changavi

    2015-01-01

    Conclusion: EGFR is an important marker to stratify patients with breast cancer according to molecular classification. Its expression correlated positively with young age, higher SBR grade, necrosis, lymphocytic infiltrate and inversely with hormonal receptor expression.

  16. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097, Paclitaxel, and Carboplatin Before Surgery in Treating Patients With Stage II or Stage III Triple-Negative Breast Cancer

    Science.gov (United States)

    2015-09-03

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  17. Triple negative breast cancer: an Indian perspective

    Directory of Open Access Journals (Sweden)

    Akhtar M

    2015-08-01

    Full Text Available Murtaza Akhtar, Subhrajit Dasgupta, Murtuza Rangwala Department of Surgery, NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, Maharashtra, India Introduction: Breast cancer is the most common female cancer in the world. Triple negative breast cancer (TNBC is a recently identified biological variant with aggressive tumor behavior and poor prognosis. Data of hormonal status from the Indian population is scarce due to financial constraints in performing immunohistochemistry evaluation. The present study aims to prospectively analyze receptor status of all breast cancer patients and identify TNBC and compare their clinical profile and short term survival with other non-TNBC group. Materials and methods: All cytologically and histopathologically confirmed cases of carcinoma breast were prospectively enrolled. In a longitudinal study at tertiary care hospital in central India based on the hormonal status, they were further divided into TNBC and other groups. Comparison of risk factors, clinical profile and short-term survival was carried out. Results: A total 85 patients were enrolled and of them 37 (43.7% were TNBC. On comparing risk factors ie, age, age at menarche, total reproductive age, age at first child birth, and menopausal status – no statistical significance was observed between the TNBC and non-TNBC groups. But on comparison of clinical profile TNBC tumors were significantly large with majority of patients presenting as locally advanced breast cancer (83%. No statistical difference was observed in axillary lymph node status between two groups. TNBC tumors were histologically more aggressive (grade 3 compared to other groups. No statistically significant difference was observed in short term overall survival but all three deaths were observed in the TNBC group only and two local recurrences after surgery were observed in the TNBC group. Conclusion: TNBC forms a large proportion of carcinoma breast patients in a central

  18. Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor.

    Science.gov (United States)

    Sebastián Sebastián, C; García Mur, C; Cruz Ciria, S; Rosero Cuesta, D S; Gros Bañeres, B

    2016-01-01

    To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology.

    Science.gov (United States)

    Deftereos, Georgios; Sanguino Ramirez, Angela M; Silverman, Jan F; Krishnamurti, Uma

    2015-09-01

    GATA3 plays a role in cell proliferation and differentiation in many tissues, including breast, and it has been suggested that GATA3 expression correlates with ER expression. However, little is known on GATA3 expression in various subtypes of breast carcinoma, its utilization in cytology, and on how GATA3 performs in comparison with GCDFP-15 and mammaglobin. Eighty-four histology cases of breast carcinoma of various subtypes, including 28 triple-negative breast carcinomas, along with 20 cytology cases of metastatic breast carcinoma and 12 cytology cases of ER-positive metastatic gynecologic malignancies, were stained for GATA3, GCDFP-15, and mammaglobin. In non-triple-negative breast carcinomas (n=56), GATA3 showed 100% sensitivity, higher than GCDFP-15 (42.8%; Pcytology cases, 100% stained with GATA3, higher than GCDFP-15 (20%; Pgynecologic malignancies. Thus, in working up ER-positive metastatic malignancies GATA3 demonstrates specificity for breast.

  20. Platinum Based Chemotherapy or Capecitabine in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy

    Science.gov (United States)

    2017-10-03

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  1. Magnetic Resonance Imaging after Completion of Neoadjuvant Chemotherapy Can Accurately Discriminate between No Residual Carcinoma and Residual Ductal Carcinoma In Situ in Patients with Triple-Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Seho Park

    Full Text Available The accurate evaluation of favorable response to neoadjuvant chemotherapy (NCT is critical to determine the extent of surgery. We investigated independent clinicopathological and radiological predictors to discriminate no residual carcinoma (ypT0 from residual ductal carcinoma in situ (ypTis in breast cancer patients who received NCT.Parameters of 117 patients attaining pathological complete response (CR in the breast after NCT between January 2010 and December 2013 were retrospectively evaluated by univariate and multivariate analyses. All patients underwent mammography, ultrasound, and magnetic resonance imaging (MRI before and after NCT.There were 67 (57.3% patients with ypT0. These patients were associated with hormone receptor-negative status, human epidermal growth factor receptor-2 (HER2-negative tumors, and a higher likelihood of breast-conservation surgery. Baseline mammographic and MRI presentation of the main lesion, absence of associated microcalcifications, shape, posterior features, and absence of calcifications on ultrasound were significantly associated with ypT0. CR in mammography, ultrasound, or MRI after NCT was also related to ypT0. By multivariate analysis, independent predictors of ypT0 were the triple-negative subtype [Odds ratio (OR, 4.23; 95% confidence interval (CI, 1.11-16.09] and CR in MRI after NCT (OR, 5.23; 95% CI, 1.53-17.85. Stratified analysis by breast cancer subtype demonstrated that MRI well predicted ypT0 in all subtypes except the HER2-positive subtype. In particular, of 40 triple-negative subtypes, 22 showed CR in MRI and 21 (95.5% were ypT0 after NCT.Among imaging modalities, breast MRI can potentially distinguish between ypT0 and ypTis after NCT, especially in patients with triple-negative breast cancer. This information can help clinicians evaluate tumor response to NCT and plan surgery for breast cancer patients of all subtypes except for those with HER2-enriched tumors after NCT.

  2. Triple-negative breast cancer

    OpenAIRE

    Chacón, Reinaldo D; Costanzo, María V

    2010-01-01

    Perou's molecular classification defines tumors that neither express hormone receptors nor overexpress HER2 as triple-negative (TN) tumors. These tumors account for approximately 15% of breast cancers. The so-called basaloid tumors are not always synonymous with TN tumors; they differ in the fact that they express different molecular markers, have a higher histologic grade, and have a worse prognosis. Clinically they occur in younger women as interval cancer, and the risk of recurrence is hig...

  3. Decorin protein core affects the global gene expression profile of the tumor microenvironment in a triple-negative orthotopic breast carcinoma xenograft model.

    Directory of Open Access Journals (Sweden)

    Simone Buraschi

    Full Text Available Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal and Homo sapiens (epithelial tissue origins. We found that decorin protein core modulated the differential expression of 374 genes within the stromal compartment of the tumor xenograft. Further, our top gene ontology classes strongly suggests an unexpected and preferential role for decorin protein core to inhibit genes necessary for immunomodulatory responses while simultaneously inducing expression of those possessing cellular adhesion and tumor suppressive gene properties. Rigorous verification of the top scoring candidates led to the discovery of three genes heretofore unlinked to malignant breast cancer that were reproducibly found to be induced in several models of tumor stroma. Collectively, our data provide highly novel and unexpected stromal gene signatures as a direct function of systemic administration of decorin protein core and reveals a fundamental basis of action for decorin to modulate the tumor stroma as a biological mechanism for the ascribed anti-tumorigenic properties.

  4. Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

    Science.gov (United States)

    2017-11-06

    Bilateral Breast Carcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

  5. Genetic Susceptibility to Triple Negative Breast Cancer

    OpenAIRE

    Stevens, Kristen N.; Vachon, Celine M.; Couch, Fergus J.

    2013-01-01

    Triple negative breast cancers (TNBC), defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression, account for 12-24% of all breast cancers. TNBC is associated with early recurrence of disease and poor outcome. Germline mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes have been associated with up to 15% of TNBC, and TNBC accounts for 70% of breast tumors arising in BRCA1 mutation carriers and 16-23% of breast ...

  6. Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-04

    Estrogen Receptor Negative; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  7. Features of triple-negative breast cancer

    OpenAIRE

    Plasilova, Magdalena L.; Hayse, Brandon; Killelea, Brigid K.; Horowitz, Nina R; Chagpar, Anees B.; Donald R. Lannin

    2016-01-01

    Abstract The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC w...

  8. Adjuvant Therapy of Triple Negative Breast Cancer

    OpenAIRE

    Perez, Edith A.; Moreno-Aspitia, Alvaro; Thompson, E. Aubrey; Andorfer, Cathy A

    2010-01-01

    Patients with the triple negative subtype of breast cancer have an overall poor outcome, with earlier relapses, distinct patterns of metastases, and lack of specific targets for treatment selection. Classification of these tumors has begun to be modified by inclusion of immunohistochemistry for various markers, and gene profiling, to further characterize this subtype of breast cancer, may aid in the identification of new targeted therapies. Anthracyclines and taxanes remain the standard of ca...

  9. Targeting EGFR in Triple Negative Breast Cancer

    OpenAIRE

    Naoto T. Ueno, Dongwei Zhang

    2011-01-01

    Our preliminary data show that erlotinib inhibits Triple-negative breast cancer (TNBC) in a xenograft model. However, inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases; thus, more direct targets that regulate TNBC metastasis need to be identified to improve its therapeutic efficacy.

  10. Targeting EGFR in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Naoto T. Ueno, Dongwei Zhang

    2011-01-01

    Full Text Available Our preliminary data show that erlotinib inhibits Triple-negative breast cancer (TNBC in a xenograft model. However, inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases; thus, more direct targets that regulate TNBC metastasis need to be identified to improve its therapeutic efficacy.

  11. Clinicopathological comparison of triple negative breast cancers ...

    African Journals Online (AJOL)

    Key words: Basal subtype, estrogen receptor, hormone receptors, human epidermal growth factor receptor‑2/neu, progesterone receptor, triple negative. Date of Acceptance: 10‑Nov‑2014. Introduction. Breast cancer is by far the most frequent cancer among women worldwide with an estimated 1.38 million new cases of ...

  12. A Study of Neoadjuvant Paclitaxel in Combination With Bavituximab in Early- Stage Triple- Negative Breast Cancer

    Science.gov (United States)

    2017-03-08

    Breast Cancer; Triple Negative Breast Neoplasms; Triple-Negative Breast Neoplasm; Triple-Negative Breast Cancer; Triple Negative Breast Cancer; ER-Negative PR-Negative HER2-Negative Breast Neoplasms; ER-Negative PR-Negative HER2-Negative Breast Cancer

  13. Triple Negative Breast Cancer – An Overview

    OpenAIRE

    Aysola, Kartik; Desai, Akshata; Welch, Crystal; Xu, Jingyao; QIN, YUNLONG; REDDY, VAISHALI; Matthews,Roland; Owens, Charlotte; Okoli, Joel; Beech, Derrick J; Piyathilake, Chandrika J.; Reddy, Shyam P; Rao, Veena N.

    2013-01-01

    Triple Negative Breast Cancer (TNBC) is a heterogeneous disease that based on immunohistochemistry (IHC) is estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER2) negative. TNBC is typically observed in young AA women and Hispanic women who carry a mutation in the BRCA1 gene. TNBC is characterized by a distinct molecular profile, aggressive nature and lack of targeted therapies. The purpose of this article is to review the curr...

  14. Triple Negative Breast Cancer in Pregnancy and Postpartum: Two Case Reports in Hispanic Women

    Directory of Open Access Journals (Sweden)

    Ruchi Upadhyay

    2015-01-01

    Full Text Available Objective. Despite studies suggesting that triple negative breast cancer is more often seen in women of African ancestry, we report here two cases of pregnancy associated triple negative breast cancer in Hispanic women. Cases. Case one is a 37-year-old female para 2-0-0-2, who presented with a left breast mass, at 19 weeks of gestation, the biopsy of which reported an invasive ductal carcinoma, found to be triple receptor negative. The patient underwent chemotherapy during the pregnancy and was delivered with a cesarean at 37 weeks for obstetric indication. After delivery, the patient completed her chemotherapy that was followed by radical mastectomy and radiotherapy. Case two is a 28-year-old female para 6-0-1-5, who presented while breast-feeding with signs and symptoms of mastitis, and an engorged and tender right breast, five months postpartum. However, the sonogram revealed a fluid filled cavity. Aspiration and cytology did not reflect an infection and were negative for malignancy. High suspicion and lack of improvement led to biopsy that identified an invasive ductal carcinoma, found to be triple negative. The patient underwent chemotherapy followed by modified radical mastectomy. Conclusions. Triple negative breast cancer, during pregnancy or postpartum, poses a unique challenge and requires a multidisciplinary team to optimize treatment for these women.

  15. Viral Therapy In Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer or Metastatic Breast Cancer

    Science.gov (United States)

    2018-02-16

    Estrogen Receptor Negative; Estrogen Receptor Positive; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; HER2/Neu Positive; Invasive Breast Carcinoma; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Head and Neck Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  16. Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD...SUBTITLE Targeting Prolyl Peptidases in Triple-Negative Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0025 5c. PROGRAM ELEMENT NUMBER 6...ABSTRACT Triple negative breast cancer (TNBC) is an aggressive sub-type with limited treatment options and poor prognosis. The most life-threatening

  17. Proteomic profiling of triple-negative breast carcinomas in combination with a three-tier orthogonal technology approach identifies Mage-A4 as potential therapeutic target in estrogen receptor negative breast cancer

    DEFF Research Database (Denmark)

    Cabezón, Teresa; Gromova, Irina; Gromov, Pavel

    2013-01-01

    receptor 2 (Her2)-positive breast tumors. However, a significant proportion of primary breast cancers are negative for ER, progesterone receptor (PgR), and Her2, comprising the triple negative breast cancer (TNBC) group. Women with TNBC have a poor prognosis because of the aggressive nature of these tumors......Breast cancer is a very heterogeneous disease, encompassing several intrinsic subtypes with various morphological and molecular features, natural history and response to therapy. Currently, molecular targeted therapies are available for estrogen receptor (ER)(-) and human epidermal growth factor....... The high level expression of Mage-A4 in the tumors studied allowed the detection of the protein in the tumor interstitial fluids as well as in sera. The existence of immunotherapeutics approaches specifically targeting this protein, or Mage-A protein family members, and the fact that we were able to detect...

  18. Immunohistochemical characterization of molecular classification of breast carcinoma and its relation with Ki-67

    OpenAIRE

    Shabnam Karangadan; Anuradha Ganesh Patil; Sainath Karnappa Andola

    2016-01-01

    Background: Breast carcinoma is the leading cause of cancer deaths in women. Molecular classification of breast carcinoma along with Ki-67 index is considered a better predictive factor for prognosis and treatment than routine histopathology. Aims: To classify breast carcinoma into the four molecular subtypes defined by immunohistochemical expression of triple markers: Luminal A (estrogen receptor/progesterone receptor-positive [ER/PR+] and human epidermal growth factor receptor 2 HER2/neu), ...

  19. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... of the role of vitronectin in tumour biology in interaction with the plasminogen activation system and integrins....

  20. METAPLASTIC CARCINOMA OF THE BREAST: A CLINICOPATHOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    Sunil Vitthalrao

    2016-04-01

    Full Text Available INTRODUCTION Metaplastic carcinoma of the breast (MCB denotes a heterogeneous group of rare malignant tumour of the breast expressing epithelial and/or mesenchymal tissue within the same tumour. AIMS To evaluate the clinicopathological features of 11 cases of metaplastic breast carcinoma in surgically excised malignant breast tumours in 8 years from April 2008 to March 2016. MATERIALS AND METHODS Total 284 consecutive cases of malignant breast lumps were removed surgically during study period, out of which 11 cases were diagnosed to have metaplastic breast carcinoma and were studied for its clinical features, size, site, gross morphological features, histopathological diagnosis, ER, PR, HER2 status, lymph node status. OBSERVATIONS Out of total 11 cases, 4 cases showed epithelial (tumour expressing adenocarcinoma and squamous cell carcinoma or squamous cell carcinoma alone, 6 cases showed biphasic (tumour expressing carcinoma and sarcomatoid or spindle cell component and 1 case showed monophasic (tumour exclusively of sarcomatoid or spindle cell component. The mean age of the patient was 44 years, 8 cases were triple ER/PR/HER2 negative. Largest tumour size was 16 cm with mean size of 7 cm. Only 3 cases showed lymph node metastasis on histopathology. CONCLUSION In our study of metaplastic breast carcinoma, patients were found to be younger–mean age 44 years, as compared with other studies of metaplastic breast carcinomas. Clinically, they had bigger size of tumour–mean 7 cm, at presentation, aggressive course with low regional lymph node metastasis-27.3%. Most of these cases were triple negative (72.7% for ER, PR and HER2 on immunohistochemical study.

  1. Salivary gland-like breast carcinomas: An infrequent disease.

    Science.gov (United States)

    Sherwell-Cabello, Santiago; Maffuz-Aziz, Antonio; Ríos-Luna, Nina Paola; Bautista-Piña, Verónica; Rodríguez-Cuevas, Sergio

    2016-11-01

    To show the incidence, as well as the clinical and histopathological characteristics, of patients diagnosed with mammary salivary gland-like carcinomas at our institution. A retrospective study was conducted in all women diagnosed with breast cancer at our institution from January 2005 to February 2016. Patients with diagnosis of salivary gland-like breast carcinomas were included. In this period, 6384 patients were diagnosed with breast cancer at our institution; salivary gland-like carcinomas were found in 7 patients (0.1%), adenoid cystic carcinoma was diagnosed in 5 patients (0.07%), acinic cell carcinoma in 1 patient (0.015%) and mucoepidermoid carcinoma in 1 patient (0.015%). The triple-negative subtype was found in all of the tumors. Median follow-up was 66.3 months (range, 1-108 months). No patient developed local or distant recurrence. Salivary gland-like breast tumors are extremely rare. We found a global incidence of 0.1%. Adenoid cystic, acinic cell and mucoepidermoid carcinomas were the three histologic types diagnosed. Although the triple-negative subtype is mainly found, good prognosis is expected. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Mucinous carcinoma occurring in the male breast

    OpenAIRE

    Ishida, Mitsuaki; UMEDA, TOMOKO; KAWAI, YUKI; MORI, Tsuyoshi; Kubota, Yoshihiro; ABE, Hajime; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Tani, Tohru; Okabe, Hidetoshi

    2013-01-01

    Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast...

  3. Does Lactation Mitigate Triple Negative/Basal Breast Cancer Progression

    Science.gov (United States)

    2013-11-01

    Award Number: W81XWH-10-1-0679 TITLE: DOES LACTATION MITIGATE TRIPLE NEGATIVE/BASAL BREAST CANCER...2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER DOES LACTATION MITIGATE TRIPLE NEGATIVE/BASAL BREAST CANCER PROGRESSION? 5b. GRANT NUMBER...that this protective layer may be maintained by tumors formed during pregnancy lactation cycle, but may be preferentially compromised by tumors

  4. Elastographic features of triple negative breast cancers.

    Science.gov (United States)

    Džoić Dominković, Martina; Ivanac, Gordana; Kelava, Tomislav; Brkljačić, Boris

    2016-04-01

    To evaluate shear-wave elastographic (SWE) features of triple negative breast cancers (TNBC) and determine useful discriminators from other types of invasive breast cancers. SWE features of 26 TNBC were reviewed and compared to 32 non-TNBC. Qualitative SWE features of lesion colour appearance, shape and homogeneity were analysed. Quantitative features were measured: mean (El mean), maximum (El max) and minimum (El min) elasticity value of the stiffest portion of the mass, mean elasticity of the surrounding tissue (El mean surr) and lesion to fat elasticity ratio (E ratio). TNBC are more often regularly shaped (57.7 % vs. 6.2 %), while non-TNBC are more commonly red (93.7 % vs 42.3 %) and heterogeneous (68.7 % vs 42.3 %). The stiffness of TNBC is significantly lower compared to non-TNBC. The two groups could be distinguished on the basis of El max (p = 0.001), El mean (p = 0.001), El min (p = 0.001) and E ratio (p = 0.0017). Lesion to fat elasticity ratio in TNBC group was statistically significantly lower than in the non-TNBC control group (p = 0.009). TNBC often demonstrate benign morphological features, are softer on SWE and have a lower lesion to fat stiffness ratio compared to the other, more common types of invasive breast cancers. • TNBC often demonstrate benign morphological features on SWE. • TNBC present on elastography mostly as red, regularly shaped, heterogeneous lesions. • TNBC are less stiff compared to other invasive breast cancers. • TNBC have lower lesion to fat stiffness ratio than other breast cancers.

  5. Hypermethylation of BRCA1 gene: implication for prognostic biomarker and therapeutic target in sporadic primary triple-negative breast cancer.

    Science.gov (United States)

    Zhu, X; Shan, L; Wang, F; Wang, J; Wang, F; Shen, G; Liu, X; Wang, B; Yuan, Y; Ying, J; Yang, H

    2015-04-01

    Paraffin sections from 239 cases of surgical resected mammary gland carcinomas were assessed to determine the role of BRCA1 gene methylation in sporadic triple-negative breast cancer and to evaluate the relationship between BRCA1 gene methylation and clinicopathologic features of triple-negative breast cancer in the National Cancer Center, China. Diagnostic tissues collected from patients received mastectomy in the National Cancer Center from January 1, 1999 to December 31, 2008 were reviewed. Tissue microarrays were constructed using 239 triple-negative breast cancer cases and stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, and epidermal growth factor receptor. Methylation status of the BRCA1 promoter was measured by methylation-specific PCR and analyzed against clinicopathologic characteristics, subtypes, and prognosis using standard statistical methods. Among the 239 triple-negative breast cancer cases, 137 (57.3 %) showed methylation of the BRCA1. According to the immunohistochemistry results, triple-negative breast cancer cases were classified into basal-like breast cancer (60.7 %) and non-basal-like breast cancer (39.3 %). The frequency of BRCA1 methylation was significantly higher in basal-like breast cancer subtype (71.7 %) than the non-basal subtype (35.1 %). Thus, BRCA1 methylation is statistically significantly correlated with basal-like breast cancer subtype (p breast cancer. Here we demonstrated that epigenetic alteration of key tumor suppressor gene can be a promising biomarker for the prognosis of triple-negative breast cancer/basal-like breast cancer. Specifically our finding revealed that BRCA1 methylation is closely associated with a significant decrease in overall survival and disease-free survival, highlighting BRCA1 promoter methylation as promising and powerful biomarkers for effect and better prognosis of DNA damaging agents for triple-negative breast cancer/basal-like breast

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

    NARCIS (Netherlands)

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

    2011-01-01

    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

  7. CYTOPATHOLOGICAL CHARACTERISTICS OF BREAST CARCINOMA

    Directory of Open Access Journals (Sweden)

    Jelena Dakovic

    2005-04-01

    Full Text Available Continual increasing of breast cancer in young women, its rare discovery in the early stage (stage I, as well as high mortality from this disease, are the facts that explain why the breast cancer is a target for many scientists. Thanks to the Greek scientist Papanicolaou and his report (l928, a successful battle with the most frequent carcinoma in women - PVU carcinoma, has begun.With the development of exfoliative, brushing and fine needle aspiration cytological methods, the impressive results have been achieved. While cytologic methods are used more and more in the breast oncopathology worldwide, up to this moment their applications have been rare in our country, which is one more reason for this study reason more for this study.By using the exfoliative and fine needle aspiration cytology, 50 patients were examined. The following cells were discovered: foamy macrophages, lipoprotein background, mastitis, eritrocytes, ductal tumorous papilles, apocrine metaplasia and ductal carcinomas. Furthermore, cytological caracteristics of the breast cancers and both advantages and limitations of the cytologic methods were pointed out. It was concluded that, using cytological methods, discovery of both precancerous breast lesions and breast cancer was possible in the earli stage. Also, sufficient knowledge of histopathology was necessary for correct interpretation of cytological results because of frequent mimicry in oncologic pathology.

  8. Epigenetic Subtypes of Triple-Negative Breast Cancer

    Science.gov (United States)

    2015-10-01

    CRISPR screen to investigate mechanisms of resistance to epigenetic therapies. POC: Program Administrator Sylvia C. Lin Email: Sylvia_Lin...1 AD______________ AWARD NUMBER: W81XWH-14-1-0213 TITLE: Epigenetic Subtypes of Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR...SUBTITLE Epigenetic Subtypes of Triple-Negative Breast Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0213 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  9. Expression of dickkopf-1 and beta-catenin related to the prognosis of breast cancer patients with triple negative phenotype.

    Directory of Open Access Journals (Sweden)

    Wen-Huan Xu

    Full Text Available BACKGROUND AND AIM: We investigated the prognostic importance of dickkopf-1(DKK1 and beta-catenin expression in triple negative breast cancers. METHODS: The expression of DKK1 and beta-catenin was evaluated in breast cell lines using RT-PCR and western blot. Immunohistochemistry was used to characterize the expression pattern of DKK1 and beta-catenin in 85 triple negative breast cancers and prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression modeling. RESULTS: The expression of DKK1 was confirmed in hormone-resistant breast cell lines MDA-MB-231, MDA-MB-231-HM and MDA-MB-435. Expression of DKK1 in triple negative breast cancers correlated with cytoplasmic/nuclear beta-catenin (p = 0.000. Elevated expression of DKK1 and cytoplasmic/nuclear beta-catenin in triple negative cancers indicate poor outcome of patients. DKK1 was also a prognostic factor for patients with earlier stage or no lymph node metastasis. CONCLUSION: DKK1 together with beta-catenin might be important prognostic factors in triple negative breast carcinoma. DKK1 might be a valuable biomarker in predicting the prognosis of patients with earlier stage or no lymph node metastasis. It is possible that through further understanding of the role of Wnt/beta-catenin pathway activation, beta-catenin would be a potential therapeutic target for the triple negative breast cancer.

  10. Triple negative breast cancer: the role of metabolic pathways.

    Science.gov (United States)

    Dean, S J R; Rhodes, A

    2014-12-01

    The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.

  11. [Breast carcinoma metastasis into a renal cell carcinoma].

    Science.gov (United States)

    Perrin, Christophe; Talarmin, Marie; Fontaine, Aurélie; Kerbrat, Pierre; Audrain, Odile; Rioux-Leclercq, Nathalie; Chiforeanu, Dan Cristian

    2011-10-01

    We report the case of a patient carrying a right breast carcinoma whose imaging exams showed lung and bone metastasic release, and incidentally synchronous right renal tumor. Histologic examination of the renal tumor found a mammary carcinoma metastasis into a clear renal cell carcinoma. This is the second case report of breast cancer with metastasis in a resected renal clear cell carcinoma. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  12. [New trends in diagnostics and classification of breast carcinoma].

    Science.gov (United States)

    Ryska, A; Laco, J; Hornychová, H; Hornychová, E; Melichar, B

    2009-04-01

    Authors report a review of current issues in morphological, immunohistochemical and molecular-genetic diagnostics of breast carcinoma. In particular, classification of tumors based on molecular profiling (luminal, HER-2 positive, triple-negative), frequency of HER-2 positive tumors in population, as well as new approaches and pitfalls in HER-2/neu diagnostics, including current recommendations for performing the tests in the Czech Republic are discussed.

  13. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    Science.gov (United States)

    2017-06-05

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  14. Intracystic breast carcinoma: case study and review.

    Science.gov (United States)

    Alipour, Sadaf; Mood, Narges Izadi

    2010-12-01

    Breast carcinoma is the most common cancer in women, the second leading cause of cancer-related mortality in women, and the leading cause of death from cancer in women between the ages of 40 and 44. While cystic breast disease is the most frequent cause of benign breast masses, intracystic breast cancers are rare. We present a case of a postmenopausal woman with a large cystic breast carcinoma with its interesting radiologic and cytopathologic findings and review the literature.

  15. Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells

    DEFF Research Database (Denmark)

    Lim, Hooi Ching; Multhaupt, Hinke A. B.; Couchman, John R.

    2015-01-01

    phenotype of mammary carcinoma cells. Finally, both syndecan-2 and caveolin-2 were upregulated in tissue arrays from breast cancer patients compared to normal mammary tissue. Moreover their expression levels were correlated in triple negative breast cancers. Conclusion: Cell surface proteoglycans, notably...

  16. Expression and prognostic value of estrogen receptor β in patients with triple-negative and triple-positive breast cancer.

    Science.gov (United States)

    Guo, Liying; Zhu, Qianwen; Aisimutuola, Mulati; Yilamu, Dilimina; Liu, Sha; Jakulin, Adina

    2015-06-01

    The aim of the present study was to investigate the expression of estrogen receptor β (ERβ) in triple-negative and triple-positive breast cancer patients, and evaluate its utility as a prognostic factor. Between January 2000 and December 2010, primary tumor tissue samples were collected from 234 subjects, including 107 triple-negative and 127 triple-positive breast cancer patients. The samples were embedded in paraffin and immunohistochemical staining was conducted to determine the expression levels of ERβ. The Kaplan-Meier method was used to analyze patient survival rates. ERβ expression was observed in 38/107 patients (35.5%) with triple-negative breast cancer and 63/127 patients (49.6%) with triple-positive breast cancer. The ERβ expression rate was significantly decreased in the patients with triple-negative breast cancer, as compared with those with triple-positive breast cancer (P=0.03). Analysis of the survival rates indicated that patients with triple-negative breast cancer and positive ERβ expression exhibited poor disease progression-free survival (DFS) compared with those with negative ERβ expression (P=0.021). However, no statistically significant difference was observed in the DFS between the triple-positive breast cancer patients with positive and negative ERβ expression. Therefore, the expression of ERβ varies between triple-negative and triple-positive breast cancer patients. In addition, positive expression of ERβ indicates a poor prognosis in triple-negative breast cancer patients; however, this is not the case for triple-positive breast cancer patients.

  17. A clinicopathologic study of triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Vandana L Gaopande

    2015-01-01

    Full Text Available Background: Triple negative breast cancers (TNBC are defined by absence of estrogen and progesterone receptors (ER and PR and absence of overexpression of human epidermal growth factor receptor 2 (Her2. They are associated with poor prognosis. The purpose of this study is to study the clinicopathologic parameters of TNBC such as age, tumor size, stage, grade, and lymph node involvement and compare them with nonTNBC tumors. There are many studies which have shown that TNBC are similar to basal-like breast cancers (BBC. We have found the proportion of BBC in the TNBC group using surrogate immunohistochemical (IHC markers cytokeratin5 (CK5 and epidermal growth factor receptor (EGFR. Materials and Methods : This is a retrospective study of 102 cases of carcinoma breast. Clinical records of the cases were retrieved. Histopathology slides and the IHC slides (ER, PR, Her2 were reviewed. Thus, two groups of patients were made TNBC and nonTNBC. Using the software SPSS version 16 statistical significance of the difference between clinicopathologic variables of the two groups was calculated. TNBC group was later studied for the presence of basal markers CK5 and EGFR using tissue microarray. Results: Statistically significant difference was found between the two groups in the variables such as mean age at diagnosis, mean tumor size, tumor grade, and the presence of lymphovascular invasion. Conclusions: TNBC formed 23.5% of total cases. Overall, TNBC were high grade tumors with larger size at diagnosis, presenting in younger women and showing lymphovascular invasion in a higher number of cases. 87.5% of TNBC were BBC.

  18. CLINICAL AND BIOLOGICAL RELEVANCE OF EZH2 IN TRIPLE NEGATIVE BREAST CANCER

    Science.gov (United States)

    Hussein, Yaser R.; Sood, Anil K.; Bandyopadhyay, Sudeshna; Albashiti, Bassam; Semaan, Assaad; Nahleh, Zeina; Roh, Juwon; Han, Hee Dong; Lopez-Berestein, Gabriel; Ali-Fehmi, Rouba

    2014-01-01

    The polycomb group protein, enhancer of zeste homolog 2 (EZH2), is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of EZH2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with EZH2, cytokeratin 5/6, epidermal growth factor receptor 1(EGFR) and p53. The expression of these markers was correlated with clinicopathologic variables and patients’ outcome. Furthermore, in vivo EZH2 gene silencing was achieved using siRNA incorporated into chitosan nanoparticles. Out of 261 cases of invasive breast cancer, high expression of EZH2 was detected in 87 (33%) cases, and it was strongly associated with a triple-negative breast cancer phenotype (P<.001) compared to all other non-triple negative breast cancers. Furthermore, high EZH2 was significantly associated with high histologic grade (P=.01), estrogen receptor negativity (P<.001), progesterone receptor negativity (P<.001), EGFR positivity (P=.04), and high p53 expression (P<.001). Survival analysis demonstrated that patients with high EZH2 had a poorer overall survival, compared to those with low EZH2 (P=.03), and it retained its significance as an independent prognostic factor (P=.02). In addition, EZH2 gene silencing resulted in significant reduction in tumor growth (P<.01) in the orthotopic MB-231 mouse model of breast carcinoma. Our results show that high EZH2 expression is significantly associated with triple-negative breast cancer and decreased survival. EZH2 may represent a potential therapeutic target for this aggressive disease, which warrants further investigation. PMID:22436627

  19. The most important questions in cancer research and clinical oncology : Question 1. Could the vertical transmission of human papilloma virus (HPV) infection account for the cause, characteristics, and epidemiology of HPV-positive oropharyngeal carcinoma, non-smoking East Asian female lung adenocarcinoma, and/or East Asian triple-negative breast carcinoma?

    Science.gov (United States)

    Wee, Joseph T S; Poh, Sharon Shuxian

    2017-01-16

    Specific research foci: (1) Mouse models of gamma-herpes virus-68 (γHV-68) and polyomavirus (PyV) infections during neonatal versus adult life. (2) For human papilloma virus (HPV)-positive oropharyngeal carcinoma (OPC)-(a) Asking the question: Is oral sex a powerful carcinogen? (b) Examining the evidence for the vertical transmission of HPV infection. (c) Examining the relationship between HPV and Epstein-Barr virus (EBV) infections and nasopharyngeal cancer (NPC) in West European, East European, and East Asian countries. (d) Examining the association between HPV-positive OPC and human leukocyte antigen (HLA). (3) For non-smoking East Asian female lung adenocarcinoma-(a) Examining the incidence trends of HPV-positive OPC and female lung adenocarcinoma according to birth cohorts. (b) Examining the association between female lung adenocarcinoma and HPV. (c) Examining the associations of lung adenocarcinoma with immune modulating factors. (4) For triple-negative breast carcinoma (TNBC) in East Asians-(a) Examining the association between TNBC and HPV. (b) Examining the unique epidemiological characteristics of patients with TNBC. A summary "epidemiological" model tying some of these findings together.

  20. Targeting autophagic cancer stem-cells to reverse chemoresistance in human triple negative breast cancer.

    Science.gov (United States)

    Bousquet, Guilhem; El Bouchtaoui, Morad; Sophie, Tan; Leboeuf, Christophe; de Bazelaire, Cédric; Ratajczak, Philippe; Giacchetti, Sylvie; de Roquancourt, Anne; Bertheau, Philippe; Verneuil, Laurence; Feugeas, Jean-Paul; Espié, Marc; Janin, Anne

    2017-05-23

    There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC).We found that chemoresistance was associated with large numbers of breast cancer stem-cells, and that these cancer stem-cells were neither proliferative nor apoptotic, but in an autophagic state related to hypoxia. Using relevant pharmacological models of patient-derived TNBC xenografts, we further investigated the role of autophagy in chemoresistance of breast cancer stem-cells. We demonstrated that hypoxia increased drug resistance of autophagic TNBC stem-cells, and showed that molecular or chemical inhibition of autophagic pathway was able to reverse chemoresistance.Our results support breast cancer stem-cell evaluation in pre-treatment biopsies of TNBC patients, and the need for further research on autophagy inhibition to reverse resistance to chemotherapy.

  1. Circumscribed breast carcinoma: Mammographic and sonographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Soo Young; Lee, Yul; Park, Ki Soon; Lee, Ke Sook [College of Medicine, Hallym University, Seoul (Korea, Republic of)

    1992-03-15

    Circumscribe breast cancer is a well demarcated mass with or without a lobulated border simulating a benign tumor like fibroadenoma on mammography or breast US and is reported as approximate 10% of the incidence among primary breast carcinoma(1.2). Pathologically medullary, colloid, papillary, intraductal and rarely invasive ductal carcinomas are included in this group which show the less intense desmoplastic reaction than the scirrhous type cancer, resulting in the most favorable prognosis of all carcinoma of the breast. Among 214 primary breast carcinoma during the past 8 years, we experienced 6 case of pathologically proven circumscribed breast cancer(2 cases of medullary carcinoma, 1 of colloid carcinoma, 1 of intracystic papillary carcinoma, 2 of comedo type intraductal carcinoma). Clinically 2 cases showed bloody nipple discharge from one hole of a unilateral nipple orifice. Mammography showed a well circumscribed nodule with or without partial lobular contour and no pathologic calcification. Breast sonographic findings were a well defined heterogeneous hypoechoic nodule with weak posterior acoustic enhancement. Characteristically a thin dilated lactiferous duct between the mass and the nipple on US could be detected in 2 cases which clinically was accompanied by bloody nipple discharge. Although the mammographic criteria is promising as benign tumor, the possibility of circumscribed as benign tumor, the possibility of circumscribed breast carcinoma must be considered in heterogeneous hypoechoic nodule with weak posterior acoustic enhancement in US, especially in the presence of a dilated lactiferous duct between the mass and the nipple with bloody nipple discharge.

  2. Correlation of clinicopathologic parameters and immunohistochemical features of triple-negative invasive lobular carcinoma.

    Science.gov (United States)

    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

  3. Male breast carcinoma

    Science.gov (United States)

    Meguerditchian, Ari-Nareg; Falardeau, Maurice; Martin, Ginette

    2002-01-01

    Objective To review the epidemiology, presentation, diagnosis, molecular genetics, treatment and prognosis of male breast cancer. Data sources Articles, written in English or French, selected from the Medline database (1966 to January 2001), corresponding to the key words “male breast cancer,” according to the following criteria: covering institutional experience or comparing diagnostic and treatment modalities, and epidemiologic or general reviews. Study selection Of 198 articles found 50 fulfilled the review criteria. Data synthesis Risk factors included advanced age, a positive family history, Jewish origin, black race, excess exposure to female hormones (Klinefelter’s syndrome), environmental exposure (irradiation), alcohol, obesity, higher socioeconomic or higher educational status and childlessness. Gynecomastia remains a controversial factor, this term being used for both a histologic reality and a physical finding. Advanced disease is characterized by pain, bloody discharge and skin ulceration. There is no definitive diagnostic algorithm. Experience with male breast mammography is limited, and imaging is less informative for patients under 50 years of age. Fine-needle aspiration tends to overestimate the rate of malignancy. The commonest histologic finding is infiltrating ductal adenocarcinoma. Treatment includes modified radical mastectomy, followed by cyclophosphamide–methotrexate–5-fluo-rouracil or 5-fluorouracil–Adriamycin–cyclophosphamide chemotherapy for disease of stage II or greater. Radiotherapy does not seem to add any benefit. The disease is highly receptor-positive; however, many patients discontinue tamoxifen due to side effects. The most important prognostic factors are tumour size, lymphatic invasion and axillary node status. Conclusions Because of the low incidence of male breast cancer, advances will be obtained mainly with the rapid transfer of newly gained knowledge in female mammary neoplasia. The increased use of adjuvant

  4. Case report of papillary breast carcinoma, cystic.

    Science.gov (United States)

    Anderson, Susan; Cink, Thomas

    2013-07-01

    Intracystic papillary carcinoma of the breast (ICP) is a rare form of noninvasive breast cancer. The average age of onset is 65 years. Patients with ICP have a greater than 15-year survival rate advantage compared to patients with other breast carcinomas. There have been no reports of disease-related deaths in patients with ICP and no increased risk of disease in the contralateral breast. No definitive conclusions have been made regarding adjuvant treatment; however, ICP should generally be treated like ductal carcinoma in situ (DCIS). Tamoxifen is often recommended.

  5. Trends of triple negative breast cancer research (2007?2015)

    OpenAIRE

    Wang, Yiran; Zhai, Xiao; Liu, Chuan; Wang,Ning; Wang, Yajie

    2016-01-01

    Abstract Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. However, there have been limited data to evaluate the trend of TNBC research. This study aims to investigate the trend of TNBC research and compare the contribution of research from different regions, organizations, and authors. Methods: TNBC-related publications from 2007 to 2015 were retrieved from the Web of Science database. Excel 2013 (Redmond, Washington, USA), GraphPad Prism 5 (GraphPad Pr...

  6. Myoepithelial carcinoma of the male breast: a rare case report ...

    African Journals Online (AJOL)

    ... we report, probably the first case of Myoepithelial carcinoma in a male breast with clinical features mimicking locally advanced breast carcinoma, together with illustration of pathological finding, microscopic appearance and management. Keywords: Myoepithelial carcinoma; Modified radical mastectomy; Chemotherapy ...

  7. HER2 genetic heterogeneity in breast carcinoma.

    Science.gov (United States)

    Ohlschlegel, Christian; Zahel, Katharina; Kradolfer, Doris; Hell, Margreth; Jochum, Wolfram

    2011-12-01

    To determine the frequency of HER2 genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify clinicopathological features that characterise breast carcinomas with HER2 genetic heterogeneity. 530 invasive breast carcinomas were retrospectively analysed for HER2 genetic heterogeneity, and investigated for a potential association of HER2 genetic heterogeneity with other HER2 FISH findings, clinicopathological parameters, oestrogen/progesterone receptor expression and DNA cytometric parameters in breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. The overall frequency of HER2 genetic heterogeneity was 14.7% in a cohort of 218 consecutive breast carcinomas. HER2 genetic heterogeneity was most frequent in invasive breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. Among the 151 carcinomas lacking HER2 amplification, 16.1% showed HER2 genetic heterogeneity. In an extended cohort of 345 carcinomas with a (2+) HER2 score, the frequency of HER2 genetic heterogeneity was 41%, and was associated with the absence of HER2 gene clusters, chromosome 17 polysomy, histological tumour grade, DNA ploidy category and 5c exceeding rate. HER2 genetic heterogeneity according to the ASCO/CAP definition is frequent in breast carcinoma, and is most often present in carcinomas with an equivocal (2+) HER2 score. Many carcinomas with HER2 genetic heterogeneity have a negative HER2 amplification status, although they contain a significant number of tumour cells with HER2 gene amplification. Single cell scoring of the HER2/17 centromeric probe (CEP17) ratio is necessary to identify carcinomas with HER2 genetic heterogeneity, because they lack specific clinicopathological characteristics.

  8. [Combining mastopexy and triple-plane breast augmentation in correction of breast atrophy and ptosis].

    Science.gov (United States)

    Long, Xiao; Wang, Yang; Bai, Ming; Zhao, Ru

    2015-01-01

    To investigate the application of combining mastopexy and triple-plane breast augmentation in correction of breast ptosis and atrophy. Peri-areolar incision was performed to finish the fascia and dermal suspension to correct the breast ptosis. The implant was inserted under the pectoralis major muscle through lateral lower border of the gland and a "X" shape full thickness incision was made on the pectoralis major muscle according to the new position of nipple-areolar complex. 14 patients received combined mastopexy and triple-plane breast augmentation to correct breast atrophy and mastopexy simultaneously. All the patients were regularly followed for 6-12 months. No patients suffered severe complication and the results were satisfied. "Triple-plane" breast augmentation could be safely performed with peri-areolar mastopexy with minor injury. The technique could help to ensure the balance between the gland, nipple-areolar complex and the implant.

  9. Risk of regional recurrence in triple-negative breast cancer patients: a Dutch cohort study

    NARCIS (Netherlands)

    Roozendaal, L.M. van; Smit, L.H.; Duijsens, G.H.; Vries, B. de; Siesling, S.; Lobbes, M.B.; Boer, M. de; Wilt, J.H.W. de; Smidt, M.L.

    2016-01-01

    Triple-negative breast cancer is associated with early recurrence and low survival rates. Several trials investigate the safety of a more conservative approach of axillary treatment in clinically T1-2N0 breast cancer. Triple-negative breast cancer comprises only 15 % of newly diagnosed breast

  10. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    Full Text Available Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1 as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  11. Mucinous carcinoma in a male breast

    Directory of Open Access Journals (Sweden)

    Roopak Aggarwal

    2011-01-01

    Full Text Available Male breast cancer is rare as compared to female counterpart. Pure mucinous carcinoma is an extremely rare histological subtype representing less than 1% of male breast cancers. So far very few cases of pure mucinous carcinoma of male breast have been reported in the literature, most of which were diagnosed after surgical resection. Fine-needle aspiration cytology is a well-established procedure for the evaluation of female breast masses but the diagnosis of malignancy in aspirates from male breast masses is rare. We herein present one case of mucinous carcinoma of breast in a 75-year-old male diagnosed by fine-needle aspiration and confirmed by histopathology. After a follow-up of 12 months the patient is free of any recurrence or metastasis.

  12. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

    2010-01-01

    share features suggesting common pathogenesis, we conducted a neoadjuvant trial of cisplatin in TNBC and explored specific biomarkers to identify predictors of response. PATIENTS AND METHODS Twenty-eight women with stage II or III breast cancers lacking estrogen and progesterone receptors and HER2/Neu...... (TNBC) were enrolled and treated with four cycles of cisplatin at 75 mg/m(2) every 21 days. After definitive surgery, patients received standard adjuvant chemotherapy and radiation therapy per their treating physicians. Clinical and pathologic treatment response were assessed, and pretreatment tumor......PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...

  13. Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy.

    Science.gov (United States)

    Mirandola, Leonardo; Pedretti, Elisa; Figueroa, Jose A; Chiaramonte, Raffaella; Colombo, Michela; Chapman, Caroline; Grizzi, Fabio; Patrinicola, Federica; Kast, W Martin; Nguyen, Diane D; Rahman, Rakhshanda Layeequr; Daver, Naval; Ruvolo, Peter; Post, Sean M; Bresalier, Robert S; Chiriva-Internati, Maurizio

    2017-09-26

    Breast carcinoma is a major health issue for millions of women. Current therapies have serious side effects, and are only partially effective in patients with metastatic tumors. Thus, the need for novel and less toxic therapies is urgent. Moreover, hormonal and antibody therapies effective in other subtypes are not effective in Triple Negative Breast Cancer (TNBC). Immunotherapeutic strategies directed against specific tumor-associated antigens (TAAs) and mediated by specific cytotoxic T lymphocytes (CTL) have been largely underexplored in this disease. Cancer-testis antigens (CTA) are a group of TAAs displaying the ideal characteristics of promising vaccine targets, i.e. strong immunogenicity and cancer specificity. The CTA, Sperm Protein 17 (SP17), has been found to be aberrantly expressed in different neoplasms, including ovarian and esophageal cancers, nervous system tumors and multiple myeloma, and has been suggested as a candidate target for immunotherapy. Here, we evaluated SP17 expression levels in breast cancer cell lines, invasive ductal breast carcinoma, including patients with TNBC, and adjacent non-neoplastic breast tissue, and determined whether SP17 was capable of generating SP17-specific cytotoxic T lymphocytes in vitro. We showed that SP17 is expressed in breast cancer cell lines and primary breast tumors and importantly in TNBC subtype, but not in adjacent non-tumoral breast tissue or unaffected tissues, except in male germinal cells. Furthermore, we detected specific anti-SP17 antibodies in patients' sera and we generated SP17-specific, HLA class I-restricted, cytotoxic T lymphocytes capable of efficiently killing breast cancer cells.

  14. Clinical, histomorphological, and therapeutic prognostic factors in patients with triple-negative invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Camila M. Lopes

    2015-12-01

    Full Text Available ABSTRACT Introduction: Breast cancer is the most common visceral malignancy in women, the leading cause of cancer death among women worldwide. The triple negative subgroup has poor prognosis and aggressive biological behavior. Objectives: To outline the clinical and histopathological aspects, the treatment profile, and to suggest which factors may predict poor prognosis in patients with triple-negative invasive breast cancer in the Campos Gerais region of Paraná. Methods: A retrospective observational cohort study, longitudinal, comparative, performed in a clinic of anatomic pathology in the Instituto Sul Paranaense de Oncologia, in Ponta Grossa, Paraná. The inclusion criteria were female patients with pathology report of invasive breast carcinoma, whose immunohistochemistry showed negative for hormone receptors and human epidermal growth factor receptor (HER2, diagnosed in the period between January 1, 2002 and December 31, 2012. The patients were divided into two groups, living women and patients who have died. Results: The recurrence rate, chemotherapy type, angiolymphatic invasion, tumor size, lymph node invasion, and type of surgery performed were significant variables in the univariate analysis between the groups. After Cox regression for multivariate analysis, only the angiolymphatic invasion (p = 0.012, relative risk [RR] 5.0518, confidence interval [CI] 95% 1.4261-17.8952, and tumor size (p = 0.0385, RR 1.2605, CI 95% 1.0123-1.5695 remained significant. Conclusion: The angiolymphatic invasion and tumor size proved to be risk factors for death, from all causes, in patients with triple-negative breast cancer. Differences between groups can indicate different molecular subtypes within the triple-negative phenotype.

  15. 19p13.1 is a triple-negative-specific breast cancer susceptibility locus

    DEFF Research Database (Denmark)

    Stevens, Kristen N; Fredericksen, Zachary; Vachon, Celine M

    2012-01-01

    -negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170...

  16. A triple negative breast cancer: what it is not!

    Directory of Open Access Journals (Sweden)

    Katakkar SB

    2012-02-01

    Full Text Available Suresh B KatakkarRegional Medical Oncology Hematology Leader, Centre for the North, BC Cancer Agency, Prince George, British Columbia, CanadaAbstract: The triple negative cancer is an unusual, and at the same time, a unique entity where the discordance rate is almost 18%. That means 18% of Her2 negative results will transform into a Her2 positive status and will have the affinity to spread to the central nervous system (CNS. With the identification of CD44, CD24, and ALDH1, we may be able to determine which group of triple negative breast cancer patients will have CNS metastasis. This case illustrates the Her2 expressing cells have higher CNS affinity. As the original tumor was Her2 negative, if a genomic assay was then done on this patient, we would have identified the potential of CNS involvement. In conclusion, genomic assays should be routinely done on triple negative cancers.Keywords: triple negative, breast cancer, claudin high or low, genomic microassay

  17. Triple Negative Breast Cancer Team Project — EDRN Public Portal

    Science.gov (United States)

    Triple negative breast cancers (TNBC), comprise 15-20% of breast cancers, and are associated with later stage at diagnosis, increased mortality, and occur more frequently in younger women where mammographic screening is less reliable. TNBCs are more likely to be diagnosed by physical exam than by mammographic screening. There is an unmet clinical need for biomarkers for the early detection of TNBC. Here, we are proposing the development of a plasma-based biomarker panel for the routine screening of women over the age of 40 for TNBC that can be used to identify women for further imaging.

  18. Targeted Therapies in Triple-Negative Breast Cancer

    OpenAIRE

    Marmé, Frederik; Schneeweiss, Andreas

    2015-01-01

    Triple-negative breast cancer (TNBC) is a heterogeneous disease comprised of several biologically distinct subtypes. However, treatment is currently mainly relying on chemotherapy as there are no targeted therapies specifically approved for TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. New targeted approaches are, therefore, urgently needed. Currently, bevacizumab, a monoclonal anti-vascular endothelial gr...

  19. Clear Cell Carcinoma of the Breast: A Rare Breast Cancer Subtype - Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Vilma Ratti

    2015-11-01

    Full Text Available Background: Glycogen-rich clear cell breast carcinoma is a rare histological breast cancer subtype. Its prognosis may vary depending on specific clinical and pathological characteristics such as low grade, strong positivity of estrogen receptor (ER expression and early diagnosis. Case Presentation: We present the case of a 53-year-old woman with a bleeding 10-cm-diameter mass in the left breast. The histological examination showed a poorly differentiated tumor with malignant cells characterized by abundant clear cytoplasm. The diagnosis of clear cell carcinoma was based on the histological characteristics of the tumor, and a nonmammary origin was initially ruled out. The tumor was triple negative [i.e. ER, progesterone receptor (PR and HER2 negative]. Four months after the initial locoregional treatment, the patient developed lung and distant lymph node metastases. Conclusions: Glycogen-rich clear cell carcinoma of the breast is a rare tumor. Early diagnosis, absence of lymph node metastases and ER/PR positivity are associated with a better prognosis, as in other common breast cancer subtypes.

  20. 7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)

    Science.gov (United States)

    2013-09-27

    Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Endometrial Carcinoma; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Prostate Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Triple-negative Breast Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  1. Solid papillary breast carcinoma with mucinous differentiation

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2003-01-01

    Full Text Available A case is reported of a solid variant of infiltrating papillary carcinoma of the breast with mucinous differentiation in a 74-year-old woman. Macroscopically, the tumor was solid and lobular, 4.5 cm in diameter. Light microscopy showed solid papillary invasive carcinoma mixed with infiltrating ductal carcinoma, not otherwise specified. Abundant intracellular and extracellular acid mucin produced by the solid papillary tumor cells was proven histochemically by: PAS, PAS-D, mucicarmine and alcian blue. Immunohistochemically, the papillary carcinoma cells were strongly reactive to estrogen receptors, and weakly to moderately reactive to smooth muscle actin. We suggest that papillary carcinoma of the breast could have potentially high degree of aggressiveness, and that differential diagnosis of these rare tumors might be a histopathological problem.

  2. Adenosquamous variant of metaplastic carcinoma of breast - an unusual histological variant.

    Science.gov (United States)

    Swathy, P U; Arunalatha, P; Chandramouleeswari, K; Lily, S Mary; Ramya, S

    2015-02-01

    Metaplastic carcinoma of breast refers to a heterogeneous group of neoplasms characterized by intimate admixture of adenocarcinoma with dominant areas of spindle cell, squamous cell and/ or mesenchymal differentiation. They constitute the rarest histological variant of invasive ductal carcinoma. These carcinomas have aggressive clinical behaviour and show suboptimal response to standard treatment. A 49-year-old female presented with lump in the left breast for one year. She was diagnosed as infiltrating ductal carcinoma breast with triple negative hormone status by trucut biopsy. She completed four cycles of neoadjuvant chemotherapy. Postchemotherapy, axillary nodes decreased in size but the size of the primary tumour remained the same. Hence, she underwent modified radical mastectomy and the specimen sent for histopathological examination. Grossly, there was a solitary cyst measuring 4x3cm. Histologically, cyst enclosing malignant cells which resemble mature squamous epithelial cells. Also, seen are malignant cells in glandular pattern.

  3. Triple-Negative Breast Cancer: Adjuvant Therapeutic Options

    Directory of Open Access Journals (Sweden)

    Ayca Gucalp

    2011-01-01

    Full Text Available Triple-negative breast cancer (TNBC, a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR and human epidermal growth factor receptor-2(HER2 represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.

  4. Triple-negative breast cancer: new perspectives for targeted therapies

    Directory of Open Access Journals (Sweden)

    Tomao F

    2015-01-01

    Full Text Available Federica Tomao,1 Anselmo Papa,2 Eleonora Zaccarelli,2 Luigi Rossi,2 Davide Caruso,2 Marina Minozzi,2 Patrizia Vici,3 Luigi Frati,4 Silverio Tomao21Department of Gynecology and Obstetrics, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, 2Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, 3Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy; 4Department of Molecular Medicine, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, ItalyAbstract: Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.Keywords: basal-like breast cancer, estrogen–progesterone receptors, gene-expression microarray, human epidermal growth factor receptor 2, chemotherapy, target therapy

  5. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

  6. Mucinous carcinoma of breast: A diagnostic pitfall

    Directory of Open Access Journals (Sweden)

    Magdalene KF, Sapna M, Jeevaraj TR

    2014-04-01

    Full Text Available Mucinous carcinoma is also known as mucoid carcinoma, colloid carcinoma, gelatinous carcinoma and mucin producing carcinoma. They are uncommon neoplasms of the breast and the reported incidence varies from 1-4%. Most of the mucinous carcinomas occur in older age group. FNAC can aid in diagnosis of mucinous carcinoma with only a few FNAC studies documented in literature. We present here a 56year old lady with a huge ulcerated breast mass clinically diagnosed as Malignant Phyllodes tumor. An FNAC was done which showed epithelial cell clusters with mild atypia in a background of both bluish violet and pink extracellular material. Spindle shaped cells were noted in the ground substance which led to a diagnosis of a phyllodes tumor with extensive myxoid change. Mastectomy was performed and the histopathological features confirmed a diagnosis of mucinous carcinoma. The tumor had areas showing thick collagenized fibrous septae separating tumor cell clusters and also areas of fibrosis. The pitfall in FNAC diagnosis may be due to the sampling from such an area.

  7. CLINICAL STUDY OF EARLY BREAST CARCINOMA

    Directory of Open Access Journals (Sweden)

    Kiran Kumar

    2016-01-01

    Full Text Available Carcinoma of the breast is one of the commonest cancers occurring in female and accounts for 1/3rd of all the malignant diseases occurring in them. It is mainly a disease of the developed countries and accounts for 1,00,000 deaths annually. Breast carcinoma is classified as Early breast cancer, Locally advanced breast cancer and Metastatic breast cancer. By definition early stage breast cancer constitutes breast tumors of clinical stages I, IIa and T2N1M0. Early breast cancer is the one diagnosed by mammography. Women when approaches at this stage, they can go for breast conservation surgery. Not all women are candidates for this approach, and some require mastectomy as part of their treatment. AIM To observe the incidence of early breast carcinoma with particular reference to the time taken by the patients to seek medical advice after the symptoms have developed i.e. the average time taken by the patients to seek medical advice, their appropriate management and prognosis. MATERIALS AND METHODS This prospective study was conducted over a period of 2 years from Oct-2012 to Oct-2014 in 30 female patients aged between 25-65 years who were presented with lump in breast of size ≤5cms with or without pain, with or without lymph nodes to the outpatient department. All the patients were thoroughly asked about history, examined clinically, investigated, staged and managed by surgery either Breast Conservation Surgery or Modified Radical Mastectomy. Postoperative complications were recorded and followed up regularly. RESULTS The incidence of early breast cancer in this study was 0.98% with peak age incidence between 40-60 years and duration of symptoms <6 months in 18 patients. Breast Conservation Surgery + axillary dissection + Radiotherapy was done in 23%. Prognosis was good in these patients with no local recurrence and death. CONCLUSION The prognosis of early stage breast carcinoma patients in this study was good. To have long term tumor free and

  8. Concurrent breast stroma sarcoma and breast carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Carvalho Teresa

    2010-12-01

    Full Text Available Abstract Introduction Breast cancer is one of the most important health problems in the world and affects a great number of women over the entire globe. This group of tumors rarely presents as bilateral disease and, when it does happen, normally occurs within the same histological type. We report a rare case of concurrent bilateral breast cancer with two different histology types, a breast carcinoma and a breast sarcoma, in a 42-year-old woman referred to our hospital. Case presentation A 42-year-old Caucasian woman admitted to our institute in August 1999, presented with a nodule in the left breast of 3.0 × 2.5 cm, and, in the right breast, one of 1.0 cm, suspected of malignancy and with a clinically negative armpit. Biopsies had revealed invasive mammary carcinoma (right breast and sarcoma (left breast. She was submitted to bilateral modified radical mastectomy. A histological study showed an invasive mammary carcinoma degree II lobular pleomorphic type with invasion of seven of the 19 excised axillary nodes in the right breast and, in the left breast, a sarcoma of the mammary stroma, for which the immunohistochemistry study was negative for epithelial biomarkers and positive for vimentin. Later, she was submitted for chemotherapy (six cycles of 75 mg/m2 5-fluorouracil, epirubicin and cyclophosphamide followed by radiotherapy of the thoracic wall and axillary nodes on the left. Hormone receptors were positive in the tumor of the right breast, and tamoxifen, 20 mg, was prescribed on a daily basis (five years followed by letrozole, 2.5 mg, also daily (five years. She presented no sign of negative evolution in the last consultation. Conclusion The risk of development of bilateral breast cancer is about 1% each year within a similar histological type, but it is higher in tumors with lobular histology. In this case, the patient presented, simultaneously, two histologically distinct tumors, thus evidencing a rare situation.

  9. Rad51 supports triple negative breast cancer metastasis

    Science.gov (United States)

    Wiegmans, Adrian P; Al-Ejeh, Fares; Chee, Nicole; Yap, Pei-Yi; Gorski, Julia J; Silva, Leonard Da; Bolderson, Emma; Chenevix-Trench, Georgia; Anderson, Robin; Simpson, Peter T; Lakhani, Sunil R; Khanna, Kum Kum

    2014-01-01

    In contrast to extensive studies on familial breast cancer, it is currently unclear whether defects in DNA double strand break (DSB) repair genes play a role in sporadic breast cancer development and progression. We performed analysis of immunohistochemistry in an independent cohort of 235 were sporadic breast tumours. This analysis suggested that RAD51 expression is increased during breast cancer progression and metastasis and an oncogenic role for RAD51 when deregulated. Subsequent knockdown of RAD51 repressed cancer cell migration in vitro and reduced primary tumor growth in a syngeneic mouse model in vivo. Loss of RAD51 also inhibited associated metastasis not only in syngeneic mice but human xenografts and changed the metastatic gene expression profile of cancer cells, consistent with inhibition of distant metastasis. This demonstrates for the first time a new function of RAD51 that may underlie the proclivity of patients with RAD51 overexpression to develop distant metastasis. RAD51 is a potential biomarker and attractive drug target for metastatic triple negative breast cancer, with the capability to extend the survival of patients, which is less than 6 months. PMID:24811120

  10. Management Options in Triple-Negative Breast Cancer

    Science.gov (United States)

    Minami, Christina A.; Chung, Debra U.; Chang, Helena R.

    2011-01-01

    Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date. PMID:21863131

  11. Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer.

    Science.gov (United States)

    Shan, Naing Lin; Wahler, Joseph; Lee, Hong Jin; Bak, Min Ji; Gupta, Soumyasri Das; Maehr, Hubert; Suh, Nanjoo

    2017-10-01

    Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures. In the present study, the effects of vitamin D compounds in regulating breast cancer stem-like cells and differentiation in triple-negative breast cancer were assessed. Mammosphere cultures, which enriches for breast cancer cells with stem-like properties, were used to assess the effects of 1α,25(OH)2D3 and BXL0124 on cancer stem cell markers in the triple-negative breast cancer cell line, SUM159. Vitamin D compounds significantly reduced the mammosphere forming efficiency in primary, secondary and tertiary passages of mammospheres compared to control groups. Key markers of cancer stem-like phenotype and pluripotency were analyzed in mammospheres treated with 1α,25(OH)2D3 and BXL0124. As a result, OCT4, CD44 and LAMA5 levels were decreased. The vitamin D compounds also down-regulated the Notch signaling molecules, Notch1, Notch2, Notch3, JAG1, JAG2, HES1 and NFκB, which are involved in breast cancer stem cell maintenance. In addition, the vitamin D compounds up-regulated myoepithelial differentiating markers, cytokeratin 14 and smooth muscle actin, and down-regulated the luminal marker, cytokeratin 18. Cytokeratin 5, a biomarker associated with basal-like breast cancer, was found to be significantly down-regulated by the vitamin D compounds. These results suggest that

  12. Inflammatory carcinoma of breast: The chameleon

    Directory of Open Access Journals (Sweden)

    Indranil Chakrabarti

    2017-01-01

    Full Text Available Inflammatory breast carcinoma is an extremely rare, rapidly progressive breast carcinoma which is a great masquerader and often is mistaken as an inflammatory lesion. This leads to the delay in diagnosis. Here, we report such a case where the mistaken clinical diagnosis led to it being treated with antibiotics. However, fine-needle aspiration cytology of the case saved the day. Histopathological confirmation followed by multimodal therapy was rendered, and the patient responded well to the treatment. Thus, awareness and recognition of this rare entity, which mimics various inflammatory and nonmalignant causes, is of paramount importance for the doctors and patients alike.

  13. Markers of metastatic carcinoma of breast origin.

    Science.gov (United States)

    Gown, Allen M; Fulton, Regan S; Kandalaft, Patricia L

    2016-01-01

    This review summarizes the three major breast-associated markers that can be of assistance in evaluating metastatic carcinomas for which a breast primary diagnosis is entertained. These markers include gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, and GATA3. The first two are cytoplasmic markers that show comparable sensitivities for breast cancer, although relatively few of the published studies have employed the same antibodies against the target molecule, making direct comparisons challenging. GATA3 is a nuclear transcription factor that shows superior sensitivity to GCDFP-15 and mammaglobin. However, the specificity of GATA3 can pose challenges, inasmuch as carcinomas of the bladder and other sites can show significant levels of positivity. Determination of the optimal panel of antibodies employed in a given clinical setting will thus depend on the non-breast tumours included in the differential diagnosis. © 2015 John Wiley & Sons Ltd.

  14. Ductal Carcinoma In Situ of the Breast

    Directory of Open Access Journals (Sweden)

    Richard J. Lee

    2012-01-01

    Full Text Available Ductal carcinoma in situ (DCIS of the breast represents a complex, heterogeneous pathologic condition in which malignant epithelial cells are confined within the ducts of the breast without evidence of invasion. The increased use of screening mammography has led to a significant shift in the diagnosis of DCIS, accounting for approximately 27% of all newly diagnosed cases of breast cancer in 2011, with an overall increase in incidence. As the incidence of DCIS increases, the treatment options continue to evolve. Consistent pathologic evaluation is crucial in optimizing treatment recommendations. Surgical treatment options include breast-conserving surgery (BCS and mastectomy. Postoperative radiation therapy in combination with breast-conserving surgery is considered the standard of care with demonstrated decrease in local recurrence with the addition of radiation therapy. The role of endocrine therapy is currently being evaluated. The optimization of diagnostic imaging, treatment with regard to pathological risk assessment, and the role of partial breast irradiation continue to evolve.

  15. Breast Carcinoma Occurring from Chronic Granulomatous Mastitis

    OpenAIRE

    Luqman, Mazlan; Shahrun Niza, Abdullah Suhaimi; Saladina Jaszle, Jasmin; Nani Harlina, Md Latar; Sellymiah, Adzman; Rohaizak, Muhammad

    2012-01-01

    Chronic granulomatous mastitis is known as a benign and relatively rare disorder that is often difficult to differentiate from breast carcinoma. We highlight the case of a 34-year-old woman who had recurrent episodes of right breast swelling and abscess for 8 years. These were proven to be chronic granulomatous mastitis by tissue biopsies on 3 different occasions. Her condition improved on similar courses of antibiotics and high-dose prednisolone. However, she subsequently developed progressi...

  16. Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

    Science.gov (United States)

    2017-09-06

    Inflammatory Breast Cancer; Stage IIA Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer; Stage IIB Breast Cancer; Estrogen Receptor Negative; Progesterone Receptor Negative; HER2/Neu Negative

  17. Clinical Characteristics in Patients with Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Janet Yeh

    2017-01-01

    Full Text Available Purpose. The purpose of this study was to compare and contrast the clinical characteristics of the triple negative breast cancer (TNBC and non-TNBC patients, with a particular focus on genetic susceptibility and risk factors prior to diagnosis. Methods. Our institutional database was queried for all patients diagnosed with invasive breast cancer between January 2010 and May 2016. Results. Out of a total of 1964 patients, 190 (10% patients had TNBC. The median age for both TNBC and non-TNBC was 59 years. There was a significantly higher proportion of African American and Asian patients with TNBC (p=0.0003 compared to patients with non-TNBC. BRCA1 and BRCA2 were significantly associated with TNBC (p<0.0001, p=0.0007. A prior history of breast cancer was significantly associated with TNBC (p=0.0003. There was no relationship observed between TNBC and a history of chemoprevention or patients who had a history of AH or LCIS. Conclusions. We found that having Asian ancestry, a prior history of breast cancer, and a BRCA1 or BRCA2 mutation all appear to be positively associated with TNBC. In order to develop more effective treatments, better surveillance, and improved prevention strategies, it is necessary to improve our understanding of the population at risk for TNBC.

  18. Melanocyte colonization and pigmentation of breast carcinoma

    DEFF Research Database (Denmark)

    Mele, Marco; Laurberg, Tinne; Engberg Damsgaard, Tine

    2012-01-01

    Introduction. Melanocyte colonization of breast carcinoma by nonneoplastic melanocytes of epidermal origin is a rare and serious condition first described in 1977. We report on the exceptional clinical and pathological features of this migration phenomenon in a 74-year-old patient. Discussion...

  19. Genomic landscape of adenoid cystic carcinoma of the breast.

    Science.gov (United States)

    Martelotto, Luciano G; De Filippo, Maria R; Ng, Charlotte K Y; Natrajan, Rachael; Fuhrmann, Laetitia; Cyrta, Joanna; Piscuoglio, Salvatore; Wen, Huei-Chi; Lim, Raymond S; Shen, Ronglai; Schultheis, Anne M; Wen, Y Hannah; Edelweiss, Marcia; Mariani, Odette; Stenman, Göran; Chan, Timothy A; Colombo, Pierre-Emmanuel; Norton, Larry; Vincent-Salomon, Anne; Reis-Filho, Jorge S; Weigelt, Britta

    2015-10-01

    Adenoid cystic carcinoma (AdCC) is a rare type of triple-negative breast cancer (TNBC) characterized by the presence of the MYB-NFIB fusion gene. The molecular underpinning of breast AdCCs other than the MYB-NFIB fusion gene remains largely unexplored. Here we sought to define the repertoire of somatic genetic alterations of breast AdCCs. We performed whole-exome sequencing, followed by orthogonal validation, of 12 breast AdCCs to determine the landscape of somatic mutations and gene copy number alterations. Fluorescence in situ hybridization and reverse-transcription PCR were used to define the presence of MYB gene rearrangements and MYB-NFIB chimeric transcripts. Unlike common forms of TNBC, we found that AdCCs have a low mutation rate (0.27 non-silent mutations/Mb), lack mutations in TP53 and PIK3CA and display a heterogeneous constellation of known cancer genes affected by somatic mutations, including MYB, BRAF, FBXW7, SMARCA5, SF3B1 and FGFR2. MYB and TLN2 were affected by somatic mutations in two cases each. Akin to salivary gland AdCCs, breast AdCCs were found to harbour mutations targeting chromatin remodelling, cell adhesion, RNA biology, ubiquitination and canonical signalling pathway genes. We observed that, although breast AdCCs had rather simple genomes, they likely display intra-tumour genetic heterogeneity at diagnosis. Taken together, these findings demonstrate that the mutational burden and mutational repertoire of breast AdCCs are more similar to those of salivary gland AdCCs than to those of other types of TNBCs, emphasizing the importance of histological subtyping of TNBCs. Furthermore, our data provide direct evidence that AdCCs harbour a distinctive mutational landscape and genomic structure, irrespective of the disease site of origin. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Genomic landscape of adenoid cystic carcinoma of the breast

    Science.gov (United States)

    Martelotto, Luciano G; De Filippo, Maria R; Ng, Charlotte KY; Natrajan, Rachael; Fuhrmann, Laetitia; Cyrta, Joanna; Piscuoglio, Salvatore; Wen, Huei-Chi; Lim, Raymond S; Shen, Ronglai; Schultheis, Anne M; Wen, Y Hannah; Edelweiss, Marcia; Mariani, Odette; Stenman, Göran; Chan, Timothy A; Colombo, Pierre-Emmanuel; Norton, Larry; Vincent-Salomon, Anne; Reis-Filho, Jorge S; Weigelt, Britta

    2015-01-01

    Adenoid cystic carcinoma (AdCC) is a rare type of triple-negative breast cancer (TNBC) characterized by the presence of the MYB-NFIB fusion gene. The molecular underpinning of breast AdCCs other than the MYB-NFIB fusion gene remains largely unexplored. Here we sought to define the repertoire of somatic genetic alterations of breast AdCCs. We performed whole exome sequencing, followed by orthogonal validation, of 12 breast AdCCs to determine the landscape of somatic mutations and gene copy number alterations. Fluorescence in situ hybridization and reverse transcription PCR were used to define the presence of MYB gene rearrangements and MYB-NFIB chimeric transcripts. Unlike common forms of TNBC, we found that AdCCs have a low mutation rate (0.27 non-silent mutations/Mb), lack mutations in TP53 and PIK3CA, and display a heterogeneous constellation of known cancer genes affected by somatic mutations, including MYB, BRAF, FBXW7, SMARCA5, SF3B1 and FGFR2. MYB and TLN2 were affected by somatic mutations in two cases each. Akin to salivary gland AdCCs, breast AdCCs were found to harbor mutations targeting chromatin remodeling, cell adhesion, RNA biology, ubiquitination, and canonical signaling pathway genes. We observed that although breast AdCCs had rather simple genomes, they likely display intra-tumor genetic heterogeneity at diagnosis. Taken together, these findings demonstrate that the mutational burden and mutational repertoire of breast AdCCs are more similar to those of salivary gland AdCCs than to those of other types of TNBCs, emphasizing the importance of histologic subtyping of TNBCs. Furthermore, our data provide direct evidence that AdCCs harbor a distinctive mutational landscape and genomic structure, irrespective of disease site of origin. PMID:26095796

  1. Histopathological evaluation of carcinoma of breast

    Directory of Open Access Journals (Sweden)

    R Pathak

    2016-03-01

    Full Text Available Background: Carcinoma of breast has become the major public health problem among females in developing as well as developed countries. InNepal it comprises 6% of total cancers cases and often diagnosed at advanced stage. Surgical removal or modified radical mastectomy (MRM is the most commonly used tools for disease management. The objective of this study is to identify the clinical, macroscopic and microscopic features of MRM specimens.Materials and methods: This prospective cross-sectional study was carried out at Department of Pathology, Bhaktapur Cancer Hospital, Bhaktapur, Nepal. Macroscopic and microscopic examination provided the tumor size, stage, grade, lymph node status, lympho-vascular invasion and perineural invasion. Data were collected and analyzed using SPSS 16.Results: The study comprised 112 breast cancer patients of which 109 (97.3% were females and 3 (2.7% were males. Invasive ductal carcinoma no specific type was the most common type of breast carcinoma. (84 cases accounting 75% of total cases. Carcinoma with medullary features was second most common (6 cases comprising 5.4% cases followed by lobular, papillary, apocrine, mucinious and NST mixed types. Grade II tumors were most frequent grade observed in 76.79% cases followed by Grade I (12.50% and Grade III (10.71%.Conclusion: As a conclusion invasive ductal carcinoma was the most common histological type breast cancer and the tumors were found at T2 and N3 stage i.e maximum at grade II. Our study provides prognostic significance of histo-pathological information in breast cancer management.

  2. Androgen receptor expression and its relationship with clinicopathological parameters in an Iranian population with invasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Fereshteh Mohammadizadeh

    2014-01-01

    Conclusions: AR expression was found to be frequently present in breast carcinoma in the studied population. Since half of the ER negative and half of the triple negative tumors were found to be AR positive, AR positive cases may benefit from alternative endocrine therapeutic strategies other than the conventional endocrine-targeted medications.

  3. Metastatic Breast Carcinoma to the Prostate Gland

    Directory of Open Access Journals (Sweden)

    Meghan E. Kapp

    2016-01-01

    Full Text Available Cancer of the male breast is an uncommon event with metastases to the breast occurring even less frequently. Prostate carcinoma has been reported as the most frequent primary to metastasize to the breast; however, the reverse has not been previously reported. Herein, we present, for the first time, a case of breast carcinoma metastasizing to the prostate gland. Prostate needle core biopsy revealed infiltrative nests of neoplastic epithelioid cells, demonstrated by immunohistochemistry (IHC to be positive for GATA3 and ER and negative for PSA and P501S. A prostate cocktail by IHC study demonstrated lack of basal cells (p63 and CK903 and no expression of P501S. The patient’s previous breast needle core biopsy showed strong ER positivity and negative staining for PR and HER2. Similar to the prostate, the breast was negative for CK5/6, p63, and p40. This case demonstrates the importance of considering a broad differential diagnosis and comparing histology and IHC to prior known malignancies in the setting of atypical presentation or rare tumors.

  4. Thyroid Metastasis from Breast Carcinoma Accompanied by Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Song-I Yang

    2014-07-01

    Full Text Available Metastasis to the thyroid gland is very rare. Recently, we experienced a case of thyroid metastasis from breast cancer accompanying a papillary thyroid. A 51-year-old female patient presented with a palpated lymph node on her left lateral neck. The patient had undergone a left modified radical mastectomy followed by chemotherapy and hormonal therapy 12 years prior. Ultrasonography of the neck revealed a malignant looking nodule at the left thyroid lobe, measuring 0.9 × 0.9 cm, and several cystic nodules at the right thyroid lobe. Ultrasonography of the neck additionally revealed a malignant looking lymph node at the right level VI. Fine-needle aspiration of the left thyroid lobe resulted in a diagnosis of papillary thyroid carcinoma and that of the right level VI in Hurthle cell lesion. The patient had a total thyroidectomy with selective dissection of the left neck node. Pathologic assessment of the specimen revealed metastatic carcinoma from the breast carcinoma and papillary thyroid carcinoma. Although the thyroid gland is highly vascularized, metastasis of malignant tumors to the thyroid is relatively rare and detection of metastasis shows a low frequency. So a careful evaluation of thyroid tumor should be considered in a patient with a history of other malignancy.

  5. Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1.

    Science.gov (United States)

    Pintens, S; Neven, P; Drijkoningen, M; Van Belle, V; Moerman, P; Christiaens, M-R; Smeets, A; Wildiers, H; Vanden Bempt, I

    2009-07-01

    Basal-like breast tumours, as defined by microarrays, carry a poor prognosis and therapeutic options are limited to date. Often, these tumours are defined as oestrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER-2) negative (triple negative) by immunohistochemistry (IHC), but a more complete definition should include expression of basal cytokeratins (CK5/6, CK14 or CK17) and/or human epidermal growth factor receptor 1 (HER-1). The aim of this study was to investigate to what extent CK5/6 and HER-1 characterise the group of triple negative breast cancers. Expression of CK5/6 and HER-1 was studied by IHC in 25 triple negative breast carcinomas and 32 grade-matched, non-triple-negative controls. All 57 cases were further subjected to fluorescence in situ hybridisation to investigate HER-1 gene copy number. CK5/6 and HER-1 expression was most frequent in triple negative tumours: 22 out of 25 cases (88.0%) expressed at least one of these markers (60.0% CK5/6 positive and 52.0% HER-1 positive). In the control group, CK5/6 and HER-1 expression was found in ER-negative but not in ER-positive tumours (ER negative/PR negative/HER-2 positive tumours: 20.0% CK5/6 positive and 46.7% HER-1 positive). HER-1 gene amplification was found in five cases only: four triple negative (16.0%) and one ER-negative control (ER negative/PR negative/HER-2 positive, 6.7%). Of interest, all five HER-1 amplified cases showed a remarkably homogeneous HER-1 expression pattern. Expression of CK5/6 and HER-1 is frequent in ER-negative breast cancers, in triple negative and in non-triple negative tumours. In a minority of cases, HER-1 overexpression may be caused by HER-1 gene amplification. Further studies are needed to investigate whether such cases might benefit from anti-HER-1 therapy.

  6. Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer.

    Science.gov (United States)

    Speers, Corey; Zhao, Shuang G; Chandler, Ben; Liu, Meilan; Wilder-Romans, Kari; Olsen, Eric; Nyati, Shyam; Ritter, Cassandra; Alluri, Prasanna G; Kothari, Vishal; Hayes, Daniel F; Lawrence, Theodore S; Spratt, Daniel E; Wahl, Daniel R; Pierce, Lori J; Feng, Felix Y

    2017-01-01

    Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R(2) = 0.72, p triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9-3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22-1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen

  7. Ductal carcinoma in situ of the breast

    Directory of Open Access Journals (Sweden)

    Jennifer L. Peterson

    2011-12-01

    Full Text Available Ductal carcinoma in situ (DCIS of the breast is a noninvasive form of breast cancer that has increased in incidence over the past several decades secondary to screening mammography. DCIS now represents 20–30% of all newly diagnosed cases of breast cancer. Patients with DCIS typically present with an abnormal mammogram, and diagnosis is most commonly obtained with an imageguided biopsy. Historically, mastectomy was considered the primary curative option for patients with DCIS. However, treatment of DCIS continues to evolve, and now treatment strategies also include breast-conserving therapy, which consists of local excision followed by radiation therapy or local excision alone. Multiple randomized trials have confirmed a decrease in ipsilateral breast tumor recurrence in patients treated with local excision followed by radiation therapy compared with local excision alone. Ongoing clinical trials attempt to identify a subgroup of DCIS patients at low risk for recurrence who may not benefit from radiation therapy. In addition, because the majority of ipsilateral breast tumor recurrences occur near the original primary tumor site, partial breast irradiation is currently under investigation as a treatment option for DCIS patients. Randomized trials have shown tamoxifen can reduce the risk of ipsilateral and contralateral breast tumor recurrences while the role of aromatase inhibitors is the subject of current clinical trials. DCIS represents a complex pathologic entity, and treatment optimization requires a multidisciplinary approach.

  8. Trends of triple negative breast cancer research (2007–2015)

    Science.gov (United States)

    Wang, Yiran; Zhai, Xiao; Liu, Chuan; Wang, Ning; Wang, Yajie

    2016-01-01

    Abstract Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. However, there have been limited data to evaluate the trend of TNBC research. This study aims to investigate the trend of TNBC research and compare the contribution of research from different regions, organizations, and authors. Methods: TNBC-related publications from 2007 to 2015 were retrieved from the Web of Science database. Excel 2013 (Redmond, Washington, USA), GraphPad Prism 5 (GraphPad Prism Software Inc., San Diego, CA), and VOSviewer (Leiden University, Leiden, Netherlands) software were used to analyze the trend of TNBC research. This article does not contain any studies with human participants or animals performed by any of the authors. Results: A total of 1695 papers were identified and were cited 34,078 times with a time limit of May 27, 2016. The United States accounted for 43.10% of the articles, 57.59% of the citations, and the highest H-index (64). China ranked second in total number of articles, but seventh in citation frequency (1998) and ninth in H-index (21). The journal Breast Cancer Research and Treatment had the highest number of publications. The author, Narod SA, has published the most papers in this field (30). The keyword “receptor” was mentioned the most, 1489 times, and the word “myeloid cell leukemia-1 (MCL-1)” was the latest hot spot by 2015. Conclusion: Literature growth related to TNBC is expanding rapidly in recent years. The quality of the articles from China still requires improvement. Newest progress of the TNBC research may be released by the journal Breast Cancer Research and Treatment first. Narod SA, Gonzalez-Angulo AM, and Hortobagyi GN may be good candidates for collaborative research in this field. MCL-1 is an emerging topic that should be closely observed. PMID:27861384

  9. Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles

    DEFF Research Database (Denmark)

    Andreasen, Simon; Tan, Qihua; Agander, Tina Klitmøller

    2018-01-01

    Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple......-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason...... for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast...

  10. Effect of body mass index on clinical and morphological characteristics of triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    I. B. Schepotin

    2014-01-01

    Full Text Available Triple negative breast cancer phenotype characterized by a more aggressive than other molecular types of tumor. In addition to non-modifiable clinical and pathological factors of aggressiveness of triple negative breast cancer is caused by potentially modifiable lifestyle (obesity, alcohol consumption, hypodynamia etc.. In this study we investigated the relationship between body mass index at diagnosis, clinical and morphological outcome predictors, and the impact of obesity on overall and disease-free survival of patients with triple negative breast cancer.

  11. Down’s Syndrome and Triple Negative Breast Cancer: A Rare Occurrence of Distinctive Clinical Relationship

    Directory of Open Access Journals (Sweden)

    Nandini Dey

    2017-06-01

    Full Text Available Down’s syndrome (DS, the most common genetic cause of significant intellectual disability in children and adults is caused by the trisomy of either all or a part of human chromosome 21 (HSA21. Patients with DS mostly suffer from characteristic tumor types. Although individual patients of DS are at a higher risk for acute leukemia and testicular cancers, other types of solid tumors including breast cancers are mostly uncommon and have significantly lower-than-expected age-adjusted incidence rates. Except for an increased risk of retinoblastomas, and lymphomas, the risk of developing solid tumors has been found to be lower in both children and adults, and breast cancer was found to be almost absent (Hasle H., The Lancet Oncology, 2001. A study conducted in the United States found only one death when 11.65 were expected (Scholl T et al., Dev Med Child Neurol. 1982. A recent study examined mammogram reports of women with DS treated in the largest medical facility specifically serving adults with DS in the United States. It was found that only 0.7% women with DS had been diagnosed with breast cancers (Chicoine B et al., Intellect Dev Disabil. 2015. Here we describe a case of breast cancer in a 25-year-old patient with DS. The disease was presented as lymph node positive carcinoma with alterations of tumor suppressor genes characteristic to the triple negative breast cancer subtype. Comprehensive Genomic Profiling (CGP revealed a wild-type status for BRCA1. The CGP report showed a frameshift mutation, A359fs*10 of the tumor suppressor gene INPP4B and another frameshift mutation, R282fs*63 of tumor suppressor gene TP53 in the tumor biopsy as characteristically found in triple-negative breast cancers. The VUS (Variance of Unknown Significance alteration(s were identified in ASXL1 (L1395V, NTRK1 (G18E, DDR2 (I159T, RUNX1 (amplification, ERG (amplification, SOX2 (T26A, FAM123B (G1031D, and HNF1A (A301T. Bonafide cancer-related genes of chromosome 21

  12. Unusual Metastatic Patterns of Invasive Lobular Carcinoma of the Breast

    OpenAIRE

    Sobinsky, Justin D.; Thomas D. Willson; Podbielski, Francis J.; Connolly, Mark M.

    2013-01-01

    Invasive lobular carcinoma of the breast has similar patterns of metastatic disease when compared to invasive ductal carcinoma; however, lobular carcinoma metastasizes to unusual sites more frequently. We present a 65-year-old female with a history of invasive lobular breast carcinoma (T3N3M0) treated with modified radical mastectomy and aromatase-inhibitor therapy who underwent a surveillance PET scan, which showed possible sigmoid cancer. Colonoscopy with biopsy revealed a 3 cm sigmoid aden...

  13. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

    Science.gov (United States)

    Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

  14. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

    Science.gov (United States)

    Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations. PMID:28721389

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mu Sook; Kim, Min kung; Kim, Eun kyung; Park, Byeong Woo; Oh, Ki Keun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2005-12-15

    Adenoid cystic carcinoma (ACC) is a rare variant of adenocarcinoma that usually occurs in the major salivary gland. In breast, adenoid cystic carcinoma is a very rare carcinoma accounting for less than 1% of the all breast carcinoma. It has an excellent prognosis with the lower incidence of distant metastasis and axillary lymph node involvement, and a benign looking or low suspicious findings on imaging. We will report the radiologic and pathologic finding of the adenoid cystic carcinoma that is incidentally detected in the right breast of asymptomatic 47-year-old woman, who had taken annual screening mammogram and ultrasonogram

  16. Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Pawel Domagala

    Full Text Available This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs and to poly(ADP-ribose polymerase (PARP inhibitors.Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.Thirty five (22.2% of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7% of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%, and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%. In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined were identified in the hereditary non-triple-negative group.Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

  17. Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

    Science.gov (United States)

    Domagala, Pawel; Jakubowska, Anna; Jaworska-Bieniek, Katarzyna; Kaczmarek, Katarzyna; Durda, Katarzyna; Kurlapska, Agnieszka; Cybulski, Cezary; Lubinski, Jan

    2015-01-01

    This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs) and to poly(ADP-ribose) polymerase (PARP) inhibitors. Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Thirty five (22.2%) of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7%) of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%), and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%). In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined) were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined) were identified in the hereditary non-triple-negative group. Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

  18. Breast carcinoma metastasis to the lacrimal gland

    DEFF Research Database (Denmark)

    Nickelsen, Marie N.; Von Holstein, Sarah; Hansen, Alastair B.

    2015-01-01

    A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomog...... study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis....

  19. Breast carcinoma occurring from chronic granulomatous mastitis.

    Science.gov (United States)

    Mazlan, Luqman; Suhaimi, Shahrun Niza Abdullah; Jasmin, Saladina Jaszle; Latar, Nani Harlina Md; Adzman, Sellymiah; Muhammad, Rohaizak

    2012-04-01

    Chronic granulomatous mastitis is known as a benign and relatively rare disorder that is often difficult to differentiate from breast carcinoma. We highlight the case of a 34-year-old woman who had recurrent episodes of right breast swelling and abscess for 8 years. These were proven to be chronic granulomatous mastitis by tissue biopsies on 3 different occasions. Her condition improved on similar courses of antibiotics and high-dose prednisolone. However, she subsequently developed progressive loss of vision due to an orbital tumour. She then underwent a craniotomy and left orbital decompression with excision of the tumour, which proved to be a metastatic carcinoma. A trucut biopsy of the right breast was then done and showed features consistent with an infiltrating ductal carcinoma. This case illustrates the possibility that chronic granulomatous mastitis could be a precursor for malignancy and the difficulty in differentiating one from the other. The possible mechanisms of development and the implications for future management are also discussed.

  20. "An addendum to breast cancer": the triple negative experience.

    Science.gov (United States)

    Turkman, Yasemin E; Kennedy, Holly Powell; Harris, Lyndsay N; Knobf, M Tish

    2016-09-01

    The triple negative breast cancer (TNBC) subtype, known to be aggressive with high recurrence and mortality rates, disproportionately affects African-Americans, young women, and BRCA1 carriers. TNBC does not respond to hormonal or biologic agents, limiting treatment options. The unique characteristics of the disease and the populations disproportionately affected indicate a need to examine the responses of this group. No known studies describe the psychosocial experiences of women with TNBC. The purpose of this study is to begin to fill that gap and to explore participants' psychosocial needs. An interpretive descriptive qualitative approach was used with in-depth interviews. A purposive sample of adult women with TNBC was recruited. Dominant themes were extracted through iterative and constant comparative analysis. Of the 22 participants, nearly half were women of color, and the majority was under the age of 60 years and within 5 years of diagnosis. The central theme was a perception of TNBC as "an addendum" to breast cancer. There were four subthemes: TNBC is Different: "Bottom line, it's not good"; Feeling Insecure: "Flying without a net"; Decision-Making and Understanding: "A steep learning curve"; and Looking Back: "Coulda, shoulda, woulda." Participants expressed a need for support in managing intense uncertainty with a TNBC diagnosis and in decision-making. Women with all subtypes of breast cancer have typically been studied together. This is the first study on the psychosocial needs specifically of women with TNBC. The findings suggest that women with TNBC may have unique experiences and unmet psychosocial needs.

  1. Targeted chemotherapy for triple-negative breast cancers via LHRH receptor.

    Science.gov (United States)

    Föst, Crispin; Duwe, Francesca; Hellriegel, Martin; Schweyer, Stefan; Emons, Günter; Gründker, Carsten

    2011-05-01

    Triple-negative breast cancer does not express estrogen and progesterone receptors and there is no overexpression/amplification of the HER2-neu gene. Therefore, this subtype of breast cancer lacks the benefits of specific therapies which target these receptors. About 60% of all human breast cancers express receptors for luteinizing hormone releasing hormone (LHRH, GnRH), which might be used as a target. The LHRH receptor can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone agonists such as AEZS-108 (AN-152), in which doxorubicin is linked to [D-Lys6]LHRH. In the present study we have analyzed by in vitro and in vivo experiments whether the cytotoxic LHRH agonist AEZS-108 (AN-152) induces apoptosis in triple-negative human breast cancer cells that express LHRH receptors. LHRH receptor expression in tumor biopsy specimens of triple-negative breast cancers was tested using immunohistochemistry. Cell proliferation was analyzed using alamar blue proliferation assay. Induction of apoptosis was quantified by measurement of loss of mitochondrial membrane potential. In vivo experiments were performed using nude mice bearing xenografted human breast tumors.Thirty-one of 42 triple-negative breast cancers (73.8%) expressed LHRH receptors. We could show that treatment of triple-negative but LHRH-positive MDA-MB-231, HCC1806 and HCC1937 human breast cancer cells with AEZS-108 (AN-152) resulted in apoptotic cell death in vitro via activation of caspase-3. The antitumor effects were confirmed in nude mice. AEZS-108 (AN-152) inhibited the growth of xenotransplants of triple-negative human breast cancers in nude mice completely, without any apparent side effects. The cytotoxic LHRH agonist AEZS-108 (AN-152) seems to be a suitable drug for an efficacious therapy for triple-negative breast cancers with little toxicity.

  2. Risk Factors for Triple-Negative Breast Cancer in Women Under the Age of 45 Years

    National Research Council Canada - National Science Library

    Jessica M. Dolle; Janet R. Daling; Emily White; Louise A. Brinton; David R. Doody; Peggy L. Porter; Kathleen E. Malone

    2009-01-01

    .... We undertook this study to assess the risk for triple-negative breast cancer among women 45 years of age and younger in relation to demographic/lifestyle factors, reproductive history, and oral contraceptive use...

  3. Revisiting Triple Antibiotic Irrigation of Breast Implant Pockets: A Placebo-controlled Single Practice Cohort Study

    Directory of Open Access Journals (Sweden)

    James J. Drinane, BSci

    2013-10-01

    Conclusions: Triple antibiotic breast irrigation is not associated with a significant reduction in the incidence or severity of capsular contracture compared with sterile saline when high-quality surgical technique is used.

  4. Squamous cell carcinoma of the breast : a case report

    NARCIS (Netherlands)

    Flikweert, Elvira R.; Hofstee, Mans; Liem, Mike S. L.

    2008-01-01

    Background: Squamous cells are normally not found inside the breast, so a primary squamous cell carcinoma of the breast is an exceptional phenomenon. There is a possible explanation for these findings. Case presentation: A 72-year-old woman presented with a breast abnormality suspected for breast

  5. mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors.

    LENUS (Irish Health Repository)

    Walsh, S

    2012-04-01

    Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.

  6. Pleomorphic Lobular Carcinoma in a Male Breast: A Rare Occurrence

    Directory of Open Access Journals (Sweden)

    Bhatia Rohini

    2010-01-01

    Full Text Available Carcinoma of male breast is uncommon as it accounts for 0.7% of total breast cancer. The pathology of male breast cancer is remarkably similar to that of cancers seen in women. The same histological subtypes of invasive cancer are present, although papillary carcinomas (both invasive and in situ are more common and lobular carcinomas are less common. The predominant histological type, in males, as in females, reported in large series has been infiltrating ductal carcinoma with scattered reports of infiltrating lobular carcinoma, all of them of classical type except for a single case of pleomorphic infiltrating lobular carcinoma. Herein, we describe a case of pleomorphic lobular carcinoma occurring in male breast.

  7. A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer

    OpenAIRE

    Glover, J A; Hughes, C M; Cantwell, M M; Murray, L J

    2011-01-01

    Background: Epidemiological studies have suggested a protective effect of cyclooxygenase (COX)-inhibiting non-steroidal anti-inflammatory drugs in breast cancer risk and disease progression. We performed a systematic review to evaluate the frequency of COX-2 expression in normal breast epithelium, ductal carcinoma in situ of breast (DCIS), DCIS-adjoining invasive breast cancer, microinvasive carcinoma of the breast (MICB) and invasive breast cancer. Methods: Literature searches were carried o...

  8. Local-Regional Recurrence of Triple Negative Breast Cancer after Breast-Conserving Surgery and Radiation

    Science.gov (United States)

    Freedman, Gary M.; Anderson, Penny R.; Li, Tianyu; Nicolaou, Nicos

    2010-01-01

    Purpose To study results of radiation on the local control of triple receptor negative breast cancer (negative estrogen (ER), progesterone (PR) and HER-2/neu receptors). Materials and Methods Conservative surgery and radiation were used in 753 patients with T1–T2 breast cancer. Three groups were defined by receptor status: ER or PR (+) group 1; ER and PR (−) but HER-2 (+) group 2; and triple negative (TN) group 3. Factors analyzed were age, menopause, race, stage, tumor size, node status, presentation, grade, extensive in-situ disease, margins, and systemic therapy. The primary endpoint was 5-year local-regional recurrence (LRR) isolated or total with distant metastases. Results ER and PR negative patients were statistically significantly more likely to be black, T2, have tumors detectable on both mammogram and physical exam, grade 3, and receive chemotherapy. There were no significant differences in ER and PR negative patients by Her-2 status. There was a significant difference in rates of first distant metastases (3%, 12% and 7% for groups 1, 2 and 3, respectively, p=0.009). However, the isolated 5-year LRR was not significantly different (2.3%, 4.6%, and 3.2%, respectively, p=0.36) between the 3 groups.. Conclusions Patients with TN breast cancer are not at significantly increased risk for isolated LRR at 5-years so remain appropriate candidates for breast conservation. PMID:19156929

  9. Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast cancer.

    Science.gov (United States)

    Huo, Lei; Zhang, Jinxia; Gilcrease, Michael Z; Gong, Yun; Wu, Yun; Zhang, Hong; Resetkova, Erika; Hunt, Kelly K; Deavers, Michael T

    2013-01-01

      In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers used to identify breast origin by immunohistochemistry. GCDFP-15 expression has been reported in approximately 60% of breast carcinomas and MAM expression in approximately 80%. Data on their expression in triple-negative breast cancer (TNBC) are very limited. The aim of this study was to examine the expression of these markers in TNBC to determine their utility in pathological diagnosis.   We studied the immunohistochemical (IHC) expression of GCDFP-15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP-15 staining was present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of GCDFP-15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many positive tumours had only focal staining.   Staining for GCDFP-15 and/or MAM in triple-negative carcinomas helps to confirm breast origin, but most tumours in this subgroup of breast carcinomas lack expression of either marker. © 2012 Blackwell Publishing Limited.

  10. Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Paolo Cossu-Rocca

    Full Text Available Triple Negative Breast Cancer (TNBC accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

  11. Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

    Directory of Open Access Journals (Sweden)

    Kostianets Olga

    2012-11-01

    Full Text Available Abstract Background On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. Methods Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. Results All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. Conclusions This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892

  12. Triple negative breast cancer patients presenting with low serum vitamin D levels: a case series

    Science.gov (United States)

    Khan, Yasir; Tisman, Glenn

    2009-01-01

    Introduction Serum vitamin D levels measured as 25-hydroxyvitamin D have been shown to be low in cancer patients, including breast cancer patients. However, the vitamin D status has yet to be studied in different breast cancer phenotypes: luminal A, luminal B, HER2+/ER-, and triple negative comprising the majority of basal-like. Case presentation Fifteen triple-negative breast cancer patients have presented to our medical oncology office in the last five years. Thirteen of these fifteen patients (87%) were found to be vitamin D deficient, defined as serum 25(OH)D less than 80 nmol/L, prior to initiation of adjuvant therapy. Ninety-one breast cancer patients from our office were classified as: luminal A (ER+ &/or PR+ and HER2-), luminal B (ER+ &/or PR+ and HER2+), HER2+/ER- (ER-, PR-, and HER2+), and triple-negative or basal-like (ER-, PR-, and HER2-). A normal mean was found from 78 volunteers. The breast cancer patients were found to be statistically different than the normal population. The triple-negative phenotype was found to be the most statistically different than the normal population. Conclusion The triple-negative breast cancer phenotype has the lowest average vitamin D level and the highest percentage of patients that are vitamin D deficient. These data suggests that low vitamin D levels are characteristic of the triple-negative phenotype. PMID:19830074

  13. Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

    Science.gov (United States)

    2017-02-28

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  14. Intratumor heterogeneity predicts metastasis of triple-negative breast cancer.

    Science.gov (United States)

    Yang, Fang; Wang, Yucai; Li, Quan; Cao, Lulu; Sun, Zijia; Jin, Juan; Fang, Hehui; Zhu, Aiyu; Li, Yan; Zhang, Wenwen; Wang, Yanru; Xie, Hui; Gustafsson, Jan-Åke; Wang, Shui; Guan, Xiaoxiang

    2017-09-01

    Even with the identical clinicopathological features, the ability for metastasis is vastly different among triple-negative breast cancer (TNBC) patients. Intratumor heterogeneity (ITH), which is common in breast cancer, may be a key mechanism leading to the tumor progression. In this study, we studied whether a quantitative genetic definition of ITH can predict clinical outcomes in patients with TNBC. We quantified ITH by calculating Shannon index, a measure of diversity in a population, based on Myc, epidermal growth factor receptor/centromeric probe 7 (EGFR/CEP7) and cyclin D1/centromeric probe 11 (CCND1/CEP11) copy number variations (CNVs) in 300 cells at three different locations of a tumor. Among 75 TNBC patients, those who developed metastasis had significantly higher ITH, that is Shannon indices of EGFR/CEP7 and CCND1/CEP11 CNVs. Higher Shannon indices of EGFR/CEP7 and CCND1/CEP11 CNVs were significantly associated with the development of metastasis and were predictive of significantly worse metastasis-free survival (MFS). Regional heterogeneity, defined as the difference in copy numbers of Myc, EGFR or CCND1 at different locations, was found in 52 patients. However, the presence of regional heterogeneity did not correlate with metastasis or MFS. Our findings demonstrate that higher ITH of EGFR/CEP7 and CCND1/CEP11 CNVs is predictive of metastasis and is associated with significantly worse MFS in TNBC patients, suggesting that ITH is a very promising novel prognostic factor in TNBC. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Diagnosis and minimally invasive treatment of early stage breast carcinoma

    NARCIS (Netherlands)

    van Esser, S.

    1979-01-01

    In this thesis the diagnostic work up and minimally invasive surgical treatment of early stage breast carcinoma is studied. Although the surgical treatment of breast carcinoma has improved significantly over the past decades, there is still room for improvement. On the one hand the focus is on early

  16. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  17. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumo...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  18. Metastatic Carcinoma Of The BreastWith Inguinal Lymph Node ...

    African Journals Online (AJOL)

    To report two cases of advanced breast carcinoma with metastases to the inguinal lymph nodes in two Nigerian women. The University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria. Two Nigerian women, one aged 40 years with an invasive lobular carcinoma of the right breast, and the other aged 48 yearswith ...

  19. Apocrine carcinoma of the breast: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Youn; Kang, Seok Seon; Kim, Hwa Young; Ji, Eun Kyung; Kwon, Tae Hee; Park, Hai Lin; Shim, Jeong Yun [CHA Hospital, Pochon CHA University College of Medicine, Soeul (Korea, Republic of)

    2007-08-15

    Apocrine carcinoma is a rare breast cancer and its frequency is about 0.4% of all breast cancers. Little is known about its clinical behavior and prognosis. To our knowledge, few studies have reported the radiologic appearances of apocrine carcinoma in the breast and there has been no such report from Korea. We describe the sonographic findings of a case of apocrine carcinoma in the breast. The sonographic findings are microlobulated heterogeneous hypoechoic lesion that has a central markedly hypoechoic portion and a peripheral mixture of iso and hypoechgenecity.

  20. Engineering Remotely Triggered Liposomes to Target Triple Negative Breast Cancer

    Science.gov (United States)

    Sneider, Alexandra; Jadia, Rahul; Piel, Brandon; VanDyke, Derek; Tsiros, Christopher; Rai, Prakash

    2017-01-01

    Triple Negative Breast Cancer (TNBC) continues to present a challenge in the clinic, as there is still no approved targeted therapy. TNBC is the worst sub-type of breast cancer in terms of prognosis and exhibits a deficiency in estrogen, progesterone, and human epidermal growth factor 2 (HER2) receptors. One possible option for the treatment of TNBC is chemotherapy. The issue with many chemotherapy drugs is that their effectiveness is diminished due to poor water solubility, and the method of administration directly or with a co-solvent intravenously can lead to an increase in toxicity. The issues of drug solubility can be avoided by using liposomes as a drug delivery carrier. Liposomes are engineered, biological nanoconstructs that possess the ability to encapsulate both hydrophobic and hydrophilic drugs and have been clinically approved to treat cancer. Specific targeting of cancer cell receptors through the use of ligands conjugated to the surface of drug-loaded liposomes could lessen damage to normal, healthy tissue. This study focuses on polyethylene glycol (PEG)-coated, folate conjugated, benzoporphyrin derivative (BPD)-loaded liposomes for treatment via photodynamic therapy (PDT). The folate receptor is over expressed on TNBC cells so these liposomes are targeted for greater uptake into cancer cells. PDT involves remotely irradiating light at 690 nm to trigger BPD, a hydrophobic photosensitive drug, to form reactive oxygen species that cause tumor cell death. BPD also displays a fluorescence signal when excited by light making it possible to image the fluorescence prior to PDT and for theranostics. In this study, free BPD, non-targeted and folate-targeted PEGylated BPD-loaded liposomes were introduced to a metastatic breast cancer cell line (MDA-MB-231) in vitro. The liposomes were reproducibly synthesized and characterized for size, polydispersity index (PDI), zeta potential, stability, and BPD release kinetics. Folate competition tests, fluorescence

  1. Next generation sequencing of triple negative breast cancer to find predictors for chemotherapy response

    NARCIS (Netherlands)

    Lips, Esther H; Michaut, Magali; Hoogstraat, Marlous; Mulder, Lennart; Besselink, Nicolle J M; Koudijs, Marco J; Cuppen, Edwin; Voest, Emile E; Bernards, Rene; Nederlof, Petra M; Wesseling, Jelle; Rodenhuis, Sjoerd; Wessels, Lodewyk F A

    2015-01-01

    INTRODUCTION: In triple negative breast cancers (TNBC) the initial response to chemotherapy is often favorable, but relapse and chemotherapy resistance frequently occur in advanced disease. Hence there is an urgent need for targeted treatments in this breast cancer subtype. In the current study we

  2. Invasive lobular carcinoma arising in accessory breast tissue

    OpenAIRE

    Devine, Catriona; Courtney, Carol-Ann; Deb, Rahul; Agrawal, Amit

    2013-01-01

    Background: Lobular carcinoma in accessory breast tissue is a rare occurrence. We present such a case in a 61-year-old woman. \\ud \\ud Case presentation: A skin nodule in the axillary skin on excision biopsy revealed invasive lobular carcinoma.\\ud \\ud Conclusions: Carcinoma in accessory breast tissue is uncommon especially invasive lobular type. A high index of suspicion may avoid late diagnosis.

  3. Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas

    DEFF Research Database (Denmark)

    Christensen, Lene Svendstrup; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-01-01

    , a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers...... are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas....

  4. FPA-FTIR Microspectroscopy for Monitoring Chemotherapy Efficacy in Triple-Negative Breast Cancer

    Science.gov (United States)

    Zawlik, Izabela; Kaznowska, Ewa; Cebulski, Jozef; Kolodziej, Magdalena; Depciuch, Joanna; Vongsvivut, Jitraporn; Cholewa, Marian

    2016-11-01

    Triple-negative breast cancer is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. Approximately 70% of triple-negative breast cancer patients fail to achieve a pathologic complete response (pCR) after chemotherapy due to the lack of targeted therapies for this subtype. We report here the development of a focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopic technique combined with principal component analysis (PCA) for monitoring chemotherapy effects in triple-negative breast cancer patients. The PCA results obtained using the FPA-FTIR spectral data collected from the same patients before and after the chemotherapy revealed discriminatory features that were consistent with the pathologic and clinical responses to chemotherapy, indicating the potential of the technique as a monitoring tool for observing chemotherapy efficacy.

  5. Adenoid cystic carcinoma of the male breast.

    Science.gov (United States)

    Kshirsagar, Ashok Yadavrao; Wader, J Vijay; Langade, Yogesh Bhupal; Jadhav, Kirankumar P; Zaware, Sagar Uday; Shekhar, Neeraj

    2006-01-01

    We present an 82-year-old male patient who presented with complaints of gradually an increasing ulcero-proliferative lesion with persistent mucinous discharge in the left breast. Left side-modified radical mastectomy was done. This was histopathologically diagnosed as an adenoid cystic carcinoma of the left breast. Periodic acid schiff (PAS) staining confirmed the diagnosis. Three of the five axillary lymph nodes excised were positive for malignancy. Although the patient was advised to have postoperative radiotherapy, he did not comply. After 2 years, the patient again presented with local recurrence of the disease. Wide excision of the recurrent malignant nodules over the anterior chest wall was done, and the defect was covered primarily with split thickness skin grafting. Postoperative radiation was given. For the past 9 months, the patient has maintained a regular follow-up on an outpatient basis. He does not have any evidence of recurrence of the tumor--neither locally nor distant metastasis.

  6. Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry

    OpenAIRE

    Brewster, Abenaa M; Chavez-MacGregor, Mariana; Brown, Powel

    2014-01-01

    Breast cancer incidence is increasing worldwide, and breast cancer-related mortality is highest in women of African ancestry, who are more likely to have basal-like or triple-negative breast cancer (TNBC) than are women of European ancestry. Identification of cultural, epidemiological, and genetic risk factors that predispose women of African ancestry to TNBC is an active area of research. Despite the aggressive behaviour of TNBC, achievement of a pathological complete response with chemother...

  7. CLINICAL AND BIOLOGICAL RELEVANCE OF EZH2 IN TRIPLE NEGATIVE BREAST CANCER

    OpenAIRE

    Hussein, Yaser R.; Sood, Anil K.; Bandyopadhyay, Sudeshna; Albashiti, Bassam; Semaan, Assaad; Nahleh, Zeina; Roh, Juwon; Han, Hee Dong; Lopez-Berestein, Gabriel; Ali-Fehmi, Rouba

    2012-01-01

    The polycomb group protein, enhancer of zeste homolog 2 (EZH2), is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of EZH2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with EZH2, cytokeratin 5/6, epidermal growth factor receptor 1(EGFR) and p53. The expression of these markers was correlated with ...

  8. Breast carcinoma at Coast Province General Hospital- Mombasa ...

    African Journals Online (AJOL)

    Less than 33% had chemotherapy. The majority of the patients had ductal carcinoma and most had FNAC done before surgery. Conclusion: Most patients present with breast cancer present late and do not access all the modalities of management. Breast health awareness and cancer screening would help to detect breast ...

  9. Clinical significance of the sub-classification of 71 cases mucinous breast carcinoma

    OpenAIRE

    Kashiwagi, Shinichiro; Onoda, Naoyoshi; Asano, Yuka; NODA, SATORU; Kawajiri, Hidemi; TAKASHIMA, TSUTOMU; Ohsawa, Masahiko; Kitagawa, Seiichi; Hirakawa, Kosei

    2013-01-01

    Objective Mucinous breast carcinoma (MBC) is classified into mixed mucinous breast carcinoma (MMBC) and pure mucinous breast carcinoma (PMBC) based on whether the tumor is with or without a component of invasive ductal carcinoma, respectively. PMBC is subtyped into hypocellular PMBC (PMBC-A) and hypercellular PMBC (PMBC-B). Methods Of 1,760 primary breast carcinomas, 71 were diagnosed as MBC, and were subtyped for comparison purposes. Results Seventy-one of all breast cancers (4.0%) were MBC,...

  10. TMEPAI genome editing in triple negative breast cancer cells

    Directory of Open Access Journals (Sweden)

    Bantari W.K. Wardhani

    2017-05-01

    Full Text Available Background: Clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9 is a powerful genome editing technique. It consists of RNA-guided DNA endonuclease Cas9 and single guide RNA (gRNA. By combining their expressions, high efficiency cleavage of the target gene can be achieved, leading to the formation of DNA double-strand break (DSB at the genomic locus of interest which will be repaired via NHEJ (non-homologous end joining or HDR (homology-directed repair and mediate DNA alteration. We aimed to apply the CRISPR/Cas9 technique to knock-out the transmembrane prostate androgen-induced protein (TMEPAI gene in the triple negative breast cancer cell line.Methods: Designed gRNA which targets the TMEPAI gene was synthesized, annealed, and cloned into gRNA expression vector. It was co-transfected into the TNBC cell line using polyethylenimine (PEI together with Cas9-GFP and puromycin resistant gene vector. At 24-hours post-transfection, cells were selected by puromycin for 3 days before they were cloned. Selected knock-out clones were subsequently checked on their protein levels by western blotting.Results: CRISPR/Cas9, a genome engineering technique successfully knocked-out TMEPAI in the Hs578T TNBC cell line. Sequencing shows a frameshift mutation in TMEPAI. Western blot shows the absence of TMEPAI band on Hs578T KO cells.Conclusion: TMEPAI gene was deleted in the TNBC cell line using the genomic editing technique CRISPR/Cas9. The deletion was confirmed by genome and protein analysis.

  11. The efficacy of betulinic acid in triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Daniel Weber

    2014-09-01

    Full Text Available Purpose: The treatment of triple-negative breast cancer remains a daunting challenge with the standard-of-care treatments eventually failing due to acquired drug resistance, toxic side effects and the presence of a deregulated immune response. New treatments for overcoming these drawbacks include the use of plant extracts. Study design: In this study, the efficacy of betulinic acid, a naturally abundant phytochemical exhibiting anti-inflammatory and anti-proliferative activity, has been evaluated for the treatment of triple-negative breast cancer MDA-MB-231 and MDA-MB-468 cell lines. Furthermore, the ability of betulinic acid to inhibit angiogenesis was also determined. Results: Here, we report that betulinic acid was able to inhibit the inflammatory response, inhibit angiogenesis and cause cell cycle arrest ultimately causing apoptosis in triple-negative breast cancer cells. Our findings support that the identification of naturally occurring anti-tumour compounds may provide a chemotherapeutic approach for the treatment of triple-negative breast cancer. Conclusion: Overall, our results provide a molecular basis for the ability of betulinic acid to mediate apoptosis, suppress inflammation and inhibit angiogenesis in triple-negative breast cancer cell lines.

  12. Inflammatory breast carcinoma: pathological or clinical entity?

    Science.gov (United States)

    Amparo, R S; Angel, C D; Ana, L H; Antonio, L C; Vicente, M S; Carlos, F M; Vicente, G P

    2000-12-01

    Inflammatory breast carcinoma (IBC) diagnosis is usually based in the presence of typical clinical symptoms (redness and edema in more than 2/3 of the breast), which are not always associated with pathologic characteristics (subdermal lymphatics involvement). Whether exclusively pathologic findings without clinical symptoms are sufficient for IBC diagnosis remains controversial. A retrospective analysis of 163 clinically diagnosed IBC (CIC) either with dermal lymphatics invasion or not, was compared with another group of 99 patients with dermal lymphatics invasion without clinical symptoms (occult inflammatory carcinoma) (OIC). The following clinical and pathological characteristics have been analyzed and compared: age, menopausal status, clinical axillar node involvement, symptoms duration before diagnosis, grade, estrogen receptors, presence of metastases at diagnosis, local recurrence, metastasic dissemination, disease-free (DFS) and overall survival (OS). Median age was younger in CIC (52.3 vs. 63.8 years; p metastases (7.4% vs. 1%; p = 0.02) was significantly more frequent in CIC. Negative estrogen receptors were more frequent in CIC (34.9% vs. 65.1%: p < 0.004). Five-years DFS (25.6 vs. 51.6%; p < 0.0001) and OS (28.6 vs. 40%; p < 0.05) were shorter in CIC. CIC (regardless of subdermal lymphatics involvement) must be clearly differentiated from OIC. Prognosis of CIC patients is poorer, so this two entities should be clearly differentiated when therepeutic results are reported.

  13. Triple-negative breast cancer: correlation between imaging and pathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Eun Sook; Lee, Byung Hee [Korea Cancer Centre Hospital, Department of Radiology, Seoul (Korea); Kim, Hyun-A; Noh, Woo-Chul [Korea Cancer Centre Hospital, Department of Surgery, Seoul (Korea); Kim, Min Suk [Korea Cancer Centre Hospital, Department of Pathology, Seoul (Korea); Lee, Sang-Ah [Kangwon National University, Department of Preventive Medicine, Kangwon-do (Korea)

    2010-05-15

    This study was designed to investigate the mammography and ultrasound findings of triple-negative breast cancer and to compare the results with characteristics of ER-positive/PR-negative/HER2-negative breast cancer and ER-negative/PR-negative/HER2-positive breast cancer. From January 2007 to October 2008, mammography and ultrasound findings of 245 patients with pathologically confirmed triple-negative (n = 87), ER-positive/PR-negative/HER2-negative (n = 93) or ER-negative/PR-negative/HER2-positive breast cancers (n = 65) were retrospectively reviewed. We also reviewed pathological reports for information on the histological type, histological grade and the status of the biological markers. Triple-negative breast cancers showed a high histological grade. On mammography, triple-negative breast cancers usually presented with a mass (43/87, 49%) or with focal asymmetry (19/87, 22%), and were less associated with calcifications. On ultrasound, the cancers were less frequently seen as non-mass lesions (12/87, 14%), more likely to have circumscribed margins (43/75, 57%), were markedly hypoechoic (36/75, 57%) and less likely to show posterior shadowing (4/75, 5%). Among the three types of breast cancers, ER-negative/PR-negative/HER2-positive breast cancers most commonly had associated calcifications (52/65, 79%) on mammography and were depicted as non-mass lesions (21/65, 32%) on ultrasound. Our results suggest that the imaging findings might be useful in diagnosing triple-negative breast cancer. (orig.)

  14. Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants.

    Science.gov (United States)

    Ohashi, R; Matsubara, M; Watarai, Y; Yanagihara, K; Yamashita, K; Tsuchiya, S-I; Takei, H; Naito, Z

    2017-04-01

    Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium- to large-sized nuclei, prominent nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non-PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non-PLC showed similar clinical outcomes in our follow-up period. Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate- to large-sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples. © 2016 John Wiley & Sons Ltd.

  15. Reproductive history, breast-feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study.

    Science.gov (United States)

    John, Esther M; Hines, Lisa M; Phipps, Amanda I; Koo, Jocelyn; Longacre, Teri A; Ingles, Sue A; Baumgartner, Kathy B; Slattery, Martha L; Wu, Anna H

    2018-01-13

    Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. For younger women, aged breast-fed compared to nulliparous women (OR = 2.02, 95% CI = 1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR = 0.52, 95% CI = 0.26-1.04, P trend  = 0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ≥3 full-term pregnancies (FTPs) and no or short-term (breast-feeding compared to women with 1-2 FTPs and breast-feeding ≥12 months (OR = 2.56, 95% CI = 1.22-5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the ethnic differences in TNBC incidence. Among controls aged breast-feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%) and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of FTPs in women under age 50 years. © 2018 UICC.

  16. Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer.

    Science.gov (United States)

    İyikesici, Mehmet Salih; Slocum, Abdul Kadir; Slocum, Ayshe; Berkarda, Ferhan Bulent; Kalamian, Miriam; Seyfried, Thomas N

    2017-07-07

    Triple-negative breast cancer (TNBC) is more aggressive and metastatic than other breast cancer types. Cytotoxic chemotherapy is presently the predominant systemic therapy for TNBC patients. This case report highlights the influence of metabolically supported chemotherapy (MSCT), ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen therapy (HBOT) in an overweight 29-year-old woman with stage IV (T4N3M1) triple-negative invasive ductal carcinoma of the breast. The patient presented with an observable mass in her left breast detected during a physical examination in December 2015. Magnetic resonance imaging revealed a Breast Imaging Reporting and Data System Category 5 tumor and multiple lymphadenomegaly in the left axilla. A Tru-Cut biopsy led to the diagnosis of a triple-negative nuclear grade 2 invasive ductal carcinoma. The patient was admitted to ChemoThermia Oncology Center, Istanbul, Turkey in October 2016, and a whole body (18F)-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT) scan revealed a 77 mm x 55 mm primary tumor in her left breast, multiple left pectoral and axillary lymph nodes, multiple widespread liver masses, and an upper left nodular abdominal lesion. The patient received a treatment protocol consisting of MSCT, KD, HT, and HBOT. A follow-up whole body 18F-FDG PET-CT scan in February 2017 showed a complete therapeutic response with no evidence of abnormal FDG uptake. The patient continued to receive this treatment protocol and in April 2017 underwent a mastectomy, which revealed a complete pathological response consistent with the response indicated by her PET-CT imaging. This single case study presents evidence of a complete clinical, radiological, and pathological response following a six-month treatment period using a combination of MSCT and a novel metabolic therapy in a patient with stage IV TNBC.

  17. Adenoid cystic carcinoma of the breast: a case series of six patients and literature review.

    Science.gov (United States)

    Kim, Miso; Lee, Dae-Won; Im, Jin; Suh, Koung Jin; Keam, Bhumsuk; Moon, Hyeong-Gon; Im, Seock-Ah; Han, Wonshik; Park, In Ae; Noh, Dong-Young

    2014-01-01

    Adenoid cystic carcinoma (ACC) of the breast is a very rare and indolent tumor with a favorable prognosis, despite its triple-negative status. Due to its rarity, there has been no consensus regarding treatments, and treatment guidelines have not been established. Here, we report on six patients with ACC of the breast. All of the patients initially presented with localized disease and no axillary lymph node metastases. Although some of our patients developed local recurrence or distant metastases, all patients had a favorable clinical course, and to date, none of the patients has died from complications of her disease. Here, we described the clinicopathologic features of ACC of the breast and review the current literature.

  18. The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer

    Science.gov (United States)

    Rhee, Jiyoung; Han, Sae-Won; Oh, Do-Youn; Kim, Jee Hyun; Im, Seock-Ah; Han, Wonshik; Ae Park, In; Noh, Dong-Young; Bang, Yung-Jue; Kim, Tae-You

    2008-01-01

    Background Triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer. Methods Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003. Clinicopathologic variables and clinical outcomes were evaluated. Results Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (< 35 y, p = 0.003), and higher histologic and nuclear grade (p < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for bcl-2 expression (p < 0.001), positive for the epidermal growth factor receptor (p = 0.003), and a high level of p53 (p < 0.001) and Ki67 expression (p < 0.00). The relapse rates during the follow-up period (median, 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (p = 0.004). Relapse free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer (4-year RFS rate 85.5% vs. 94.2%, respectively; p = 0.001). On multivariate analysis, young age, close resection margin, and triple-negativity were independent predictors of shorter RFS. Conclusion TN breast cancer had higher relapse rate and more aggressive clinicopathologic characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into the risk factor analysis for node-negative breast cancer. PMID:18947390

  19. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer

    Science.gov (United States)

    2009-01-01

    Background Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer. Methods We studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT) and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE). All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing. Results Five deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%). Conclusion Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer. PMID:19298662

  20. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    DeSai Damini

    2009-03-01

    Full Text Available Abstract Background Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2. The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer. Methods We studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE. All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing. Results Five deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%. Conclusion Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer.

  1. Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Nicola Ferrari

    Full Text Available The RUNX1 transcription factor is widely recognised for its tumour suppressor effects in leukaemia. Recently a putative link to breast cancer has started to emerge, however the function of RUNX1 in breast cancer is still unknown. To investigate if RUNX1 expression was important to clinical outcome in primary breast tumours a tissue microarray (TMA containing biopsies from 483 patients with primary operable invasive ductal breast cancer was stained by immunohistochemistry. RUNX1 was associated with progesterone receptor (PR-positive tumours (P<0.05, more tumour CD4+(P<0.05 and CD8+(P<0.01 T-lymphocytic infiltrate, increased tumour CD138+plasma cell (P<0.01 and more CD68+macrophage infiltrate (P<0.001. RUNX1 expression did not influence outcome of oestrogen receptor (ER-positive or HER2-positive disease, however on univariate analysis a high RUNX1 protein was significantly associated with poorer cancer-specific survival in patients with ER-negative (P<0.05 and with triple negative (TN invasive breast cancer (P<0.05. Furthermore, multivariate Cox regression analysis of cancer-specific survival showed a trend towards significance in ER-negative patients (P<0.1 and was significant in triple negative patients (P<0.05. Of relevance, triple negative breast cancer currently lacks good biomarkers and patients with this subtype do not benefit from the option of targeted therapy unlike patients with ER-positive or HER2-positive disease. Using multivariate analysis RUNX1 was identified as an independent prognostic marker in the triple negative subgroup. Overall, our study identifies RUNX1 as a new prognostic indicator correlating with poor prognosis specifically in the triple negative subtype of human breast cancer.

  2. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    Department of Pathology, ESIC Medical College and PGIMSR, Rajajinagar, Bangalore, India. Abstract. Primary neuroendocrine carcinoma (PNEC) of breast was an unknown pathologic entity till recently due ... whole body computed tomography and magnetic resonance imaging revealed no extra mammary primary tumor.

  3. Comparative evaluation of six cytological grading systems in breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kaushik Saha

    2013-01-01

    Conclusions: Robinson′s grading system is simple, more objective and reproducible, and demonstrated the best concordance with histological grading. So, Robinson′s system should be used routinely for breast carcinoma aspirates.

  4. Re-resection rates and risk characteristics following breast conserving surgery for breast cancer and carcinoma in situ

    DEFF Research Database (Denmark)

    Kryh, C G; Pietersen, C A; Rahr, Hans

    2014-01-01

    OBJECTIVES: To examine the frequency of re-resections and describe risk characteristics: invasive carcinoma or carcinoma in situ (CIS), palpability of the lesion, and neoadjuvant chemotherapy. RESULTS: 1703 breast conserving surgeries were performed: 1575 primary breast conserving surgeries (BCS)...

  5. Invasive lobular carcinoma: a rare presentation in the male breast.

    Science.gov (United States)

    Melo Abreu, Elisa; Pereira, Pedro; Marques, José Carlos; Esteves, Gonçalo

    2016-05-05

    Breast cancer in men is uncommon, accounting for lobular structures are quite infrequent in the male breast, rare cases of invasive lobular breast carcinoma have been described, representing 1-2% of all breast cancers in men. Risk factors include undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelter's syndrome, previous thoracic radiotherapy, alterations of the oestrogen-testosterone ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented. 2016 BMJ Publishing Group Ltd.

  6. Does Lactation Mitigate Triple Negative/Basal Breast Cancer Progression?

    Science.gov (United States)

    2012-09-01

    Breast Cancer Res Treat, 2008. 109(1): p. 123-39. 2. Palmer, J.R., et al., Parity and lactation in relation to estrogen receptor negative breast ...Xue F, Michels KB: Lactation and incidence of premenopausal breast cancer : a longitudinal study. Arch Intern Med 2009, 169(15):1364-1371. 19...Palmer JR, Boggs DA, Wise LA, Ambrosone CB, Adams-Campbell LL, Rosenberg L: Parity and lactation in relation to estrogen receptor negative breast cancer

  7. HER2-Positive Metaplastic Spindle Cell Carcinoma Associated with Synchronous Bilateral Apocrine Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Katsumi Kito

    2014-01-01

    Full Text Available Apocrine carcinoma, which is strictly defined as over 90% of tumor cells showing apocrine differentiation, is a rare variant of breast cancer. Here we report an uncommon case in which apocrine carcinomas developed concurrently in both breasts; in addition, a sarcomatoid spindle cell lesion was coincident in the right breast. Both apocrine carcinomas were immunohistochemically negative for estrogen receptor (ER and progesterone receptor (PgR, but diffusely positive for androgen receptor (AR, GCDFP-15, and HER2. The presence of intraductal components in bilateral carcinomas and the absence of lymph node metastasis suggested that they were more likely to be individual primary lesions rather than metastatic disease. The spindle cell lesion showed a relatively well-circumscribed nodule contiguous with the apocrine carcinoma. HER2 oncoprotein overexpression was observed not only in the apocrine carcinoma, but also in the spindle cell lesion. Since the spindle cell component was intimately admixed with apocrine carcinoma and had focal cytokeratin expression, we diagnosed it as metaplastic spindle cell carcinoma, which was originated from the apocrine carcinoma. To our knowledge, this is the first case report of a patient with synchronous bilateral apocrine carcinomas coinciding with metaplastic carcinoma.

  8. The prognostic significance of metaplastic carcinoma of the breast (MCB)--a case controlled comparison study with infiltrating ductal carcinoma.

    Science.gov (United States)

    Lai, Hung-Wen; Tseng, Ling-Ming; Chang, Tsai-Wang; Kuo, Yao-Lung; Hsieh, Chia-Ming; Chen, Shou-Tung; Kuo, Sou-Jen; Su, Chin-Cheng; Chen, Dar-Ren

    2013-10-01

    Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast cancer with an incidence of less than 0.1%-0.5%. Due to its rarity, the clinical characteristics and prognostic significance of MCB compared with other common breast cancers (like infiltrating ductal carcinoma [IDC], and infiltrating lobular carcinoma [ILC]) are not clear, and controversial among different reports. We performed a collective comparison study of multi-institutional cases to evaluate the clinical characteristics and prognostic status of MCB to compare with IDC and ILC. A case control analysis was performed to minimize the bias from clinicopathologic factors between IDC and MCB. Disease free survival (DFS) and overall survival (OS) between groups were compared. Forty-five MCB patients were enrolled from the 4 medical centers and compared with 1777 IDC and 53 ILC patients from the CCH cancer registry database comprise the current study. Compared with IDC, MCB was associated with older age, larger tumor size, a lesser lymph node positive rate, a higher likelihood of distant metastasis, higher tumor grade, lower ER-positive tumor, and higher triple negative breast cancer subtype (TNBC). MCB was associated with worse OS (p = 0.031) than IDC, but no difference in DFS (p = 0.071); however, MCB was not statistically different from ILC in both DFS and OS (p = 0.289 and 0.132, respectively). Compared with the case-controlled IDC group, MCB patients had poorer OS (p = 0.040), but no difference in DFS (p = 0.439). MCB is associated with poorer OS than IDC, and this was related to tumor behavior rather than clinicopathologic factors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Neoadjuvant Therapy in Operable Breast Cancer: Application to Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Foluso O. Ademuyiwa

    2013-01-01

    Full Text Available Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today’s standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed.

  10. Negative Expression of Melanoma Cell Adhesion Molecule (MCAM Correlated with Axillary Lymph Node Metastasis in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sartika Nurwenda

    2016-09-01

    Full Text Available Triple negative breast cancer (TNBC is breast cancer that demonstrate the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. TNBC has an aggressive behaviour, high frequency of metastasis to the axillary lymph nodes and recurrence, and poor prognosis. Metastasis to the axillary lymph nodes will affect the rate of survival and recurrence in TNBC. Melanoma cell adhession molecule (MCAM is a membrane glycoprotein of the immunoglobulin superfamily, which is involved in the cells binding, which later became known as the marker for the progression and metastasis of melanoma and carcinoma of the prostate. However, MCAM role in mammary carcinoma still controversial. The aim of this study was to assess correlation between MCAM expression with incidence of metastatic to axillary lymph nodes in TNBC. This research was conducted during January 1st 2010–April 31st 2015 at Pathology Anatomy, Faculty of Medicine, Universitas Padjadjaran. This study used a cross-sectional design, using lambda correlation test. MCAM immunohistochemical staining performed on 56 samples of paraffin blocks of TNBC group that did not metastasized and has metastasized to the axillary lymph nodes. A total of 22 of 28 (78.6% of TNBC metastatic to axillary lymph nodes have histoskor MCAM value <4 (negative, whereas 16 of 28 (57.1% of TNBC non-metastatic have histoskor value ≥ 4 (positive. Negative expression of MCAM correlated with TNBC that had metastasized to axillary lymph nodes, although not the only factor that influenced them.

  11. Genetic predisposition to ductal carcinoma in situ of the breast

    NARCIS (Netherlands)

    C. Petridis (Christos); R.H. Brook; V. Shah (Vandna); K. Kohut (Kelly); P. Gorman (Patricia); M. Caneppele (Michele); D. Levi (Dina); E. Papouli (Efterpi); N. Orr (Nick); A. Cox (Angela); S.S. Cross (Simon); I. dos Santos Silva (Isabel); J. Peto (Julian); A.J. Swerdlow (Anthony ); M. Schoemaker (Minouk); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); J. Benítez (Javier); A. González-Neira (Anna); D.C. Tessier (Daniel C.); D. Vincent (Daniel); J. Li (Jingmei); J.D. Figueroa (Jonine); V. Kristensen (Vessela); A.-L. Borresen-Dale (Anne-Lise); P. Soucy (Penny); J. Simard (Jacques); R.L. Milne (Roger); G.G. Giles (Graham); S. Margolin (Sara); A. Lindblom (Annika); T. Brüning (Thomas); H. Brauch (Hiltrud); M.C. Southey (Melissa); J.L. Hopper (John); T. Dörk (Thilo); N.V. Bogdanova (Natalia); M. Kabisch (Maria); U. Hamann (Ute); R.K. Schmutzler (Rita); A. Meindl (Alfons); H. Brenner (Hermann); V. Arndt (Volker); R. Winqvist (Robert); K. Pykäs (Katri); P.A. Fasching (Peter); M.W. Beckmann (Matthias); J. Lubinski (Jan); A. Jakubowska (Anna); A.M. Mulligan (Anna Marie); I.L. Andrulis (Irene); R.A.E.M. Tollenaar (Rob); P. Devilee (Peter); L. Le Marchand (Loic); C.A. Haiman (Christopher); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); P. Radice (Paolo); P. Peterlongo (Paolo); F. Marme (Federick); B. Burwinkel (Barbara); C.H.M. van Deurzen (Carolien); A. Hollestelle (Antoinette); N. Miller (Nicola); M. Kerin (Michael); D. Lambrechts (Diether); O.A.M. Floris; J. Wesseling (Jelle); H. Flyger (Henrik); S.E. Bojesen (Stig); S. Yao (Song); C.B. Ambrosone (Christine); G. Chenevix-Trench (Georgia); T. Truong (Thérèse); P. Guénel (Pascal); A. Rudolph (Anja); J. Chang-Claude (Jenny); H. Nevanlinna (Heli); C. Blomqvist (Carl); K. Czene (Kamila); J.S. Brand (Judith S.); J.E. Olson (Janet); F.J. Couch (Fergus); A.M. Dunning (Alison); P. Hall (Per); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); S. Pinder (Sarah); M.K. Schmidt (Marjanka); I.P. Tomlinson (Ian); R. Roylance (Rebecca); M. García-Closas (Montserrat); E.J. Sawyer (Elinor)

    2016-01-01

    textabstractBackground: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk

  12. Immunohistochemical categorisation of ductal carcinoma in situ of the breast

    NARCIS (Netherlands)

    Meijnen, P.; Peterse, J. L.; Antonini, N.; Rutgers, E. J. Th; van de Vijver, M. J.

    2008-01-01

    The aim of this study is to analyse whether immunohistochemistry (IHC) applying a broad set of markers could be used to categorise ductal carcinoma in situ (DCIS) of the breast in distinct subgroups corresponding to the recently defined molecular categories of invasive carcinoma.

  13. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    OpenAIRE

    Collina, Francesca; Di Bonito, Maurizio; Li Bergolis, Valeria; De Laurentiis, Michelino; Vitagliano, Carlo; Cerrone, Margherita; Nuzzo, Francesco; Cantile, Monica; Botti, Gerardo

    2015-01-01

    Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as...

  14. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

    OpenAIRE

    Feng, Tingting; Cao, Wei; Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-i; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2016-01-01

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mech...

  15. Breast imaging findings in women with BRCA1- and BRCA2-associated breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, L.J.; Evans, A.J. E-mail: aevans@ncht.trent.nhs.uk; Wilson, A.R.M.; Scott, N.; Cornford, E.J.; Pinder, S.E.; Khan, H.N.; Macmillan, R.D

    2004-10-01

    AIM: To document the breast imaging findings of women with BRCA1 and BRCA2-associated breast carcinoma. MATERIALS AND METHODS: Family history clinic records identified 18 BRCA1 and 10 BRCA2 cases who collectively were diagnosed with 27 invasive breast carcinomas and four ductal carcinoma in situ (DCIS) lesions. All underwent pre-operative imaging (29 mammogram and 22 ultrasound examinations). All invasive BRCA-associated breast carcinoma cases were compared with age-matched cases of sporadic breast carcinoma. RESULTS: Within the BRCA cases the age range was 26-62 years, mean 36 years. Two mammograms were normal and 27 (93%) abnormal. The most common mammographic features were defined mass (63%) and microcalcifications (37%). Thirty-four percent of women had a dense mammographic pattern, 59% mixed and 7% fatty. Ultrasound was performed in 22 patients and in 21 (95%) indicated a mass. This was classified as benign in 24%, indeterminate in 29% and malignant in 48%. Mammograms of BRCA1-associated carcinomas more frequently showed a defined mass compared with BRCA2-associated carcinomas, 72 versus 36% (73% control group) whilst mammograms of BRCA2-associated carcinomas more frequently showed microcalcification, 73 versus 12% (8% control group; p<0.001). Thirty-six percent of the BRCA2-associated carcinomas were pure DCIS while none of the BRCA1 associated carcinomas were pure DCIS (p=0.004). Of those patients undergoing regular mammographic screening, 100% of BRCA2-associated carcinomas were detected compared with 75% of BRCA1-associated carcinomas. CONCLUSION: These data suggest that the imaging findings of BRCA1 and BRCA2-associated carcinomas differ from each other and from age-matched cases of sporadic breast carcinoma.

  16. Hypomethylation of the MMP7 promoter and increased expression of MMP7 distinguishes the basal-like breast cancer subtype from other triple-negative tumors.

    Science.gov (United States)

    Sizemore, Steven T; Sizemore, Gina M; Booth, Christine N; Thompson, Cheryl L; Silverman, Paula; Bebek, Gurkan; Abdul-Karim, Fadi W; Avril, Stefanie; Keri, Ruth A

    2014-07-01

    Identification of novel targets for the treatment of basal-like breast cancer is essential for improved outcomes in patients with this disease. This study investigates the association of MMP7 expression and MMP7 promoter methylation with subtype and outcome in breast cancer patient cohorts. Immunohistochemical analysis was performed on a breast cancer tissue microarray and validated in independent histological samples. MMP7 expression significantly correlated with patient age, tumor size, triple-negative (TN) status, and recurrence. Analysis of publically available datasets confirmed MMP7 gene expression as a prognostic marker of breast cancer metastasis, particularly metastasis to the brain and lungs. Methylation of the MMP7 promoter was assessed by methylation-specific PCR in a panel of breast cancer cell lines and patient tumor samples. Hypomethylation of the MMP7 promoter significantly correlated with TN status in DNA from patient tumor samples, and this association was confirmed using The Cancer Genome Atlas (TCGA) dataset. Evaluation of a panel of breast cancer cell lines and data from the Curtis and TCGA breast carcinoma datasets revealed that elevated MMP7 expression and MMP7 promoter hypomethylation are specific biomarkers of the basal-like molecular subtype which shares considerable, but not complete, overlap with the clinical TN subtype. Importantly, MMP7 expression was identified as an independent predictor of pathological complete response in a large breast cancer patient cohort. Combined, these data suggest that MMP7 expression and MMP7 promoter methylation may be useful as prognostic biomarkers. Furthermore, MMP7 expression and promoter methylation analysis may be effective mechanisms to distinguish basal-like breast cancers from other triple-negative subtypes. Finally, these data implicate MMP7 as a potential therapeutic target for the treatment of basal-like breast cancers.

  17. Overweight: Is It a Prognostic Factor in Women with Triple-Negative Breast Cancer?

    Science.gov (United States)

    Al Jarroudi, Ouissam; Abda, Naima; Seddik, Youssef; Brahmi, Sami Aziz; Afqir, Said

    2017-06-25

    Background: Obesity is associated with poor outcomes in patients with breast cancer expressing hormone receptors, but this association is not well established for triple-negative breast cancer. In this study, we investigated the influence of body mass index (BMI) in triple-negative breast cancer outcomes. Methods: This is a descriptive and analytical retrospective cohort study at the Regional Oncology Center Hassan II-Oujda. We identified 115 patients with triple-negative breast cancer, met the criteria for inclusion, treated between January 2009 and December 2011. The clinicopathological characteristics were collected to assess the association between BMI and overall survival and disease-free survival at 5 years, using the Kaplan-Meier and Cox model. Results: Data analysis focused on 115 patients, 34 patients (28.7%) were normal weight (BMI p = 0.001) and DFS (HR:1.899, 95% IC: 1.05 – 3.433, p=0.034) in all patients with triple-negative breast cancer. When stratified by menopausal status, overweight was associated with DFS and OS (HR : 3.242, 95% CI: 1.249 to 8.412, p = 0.016) and (HR : 2.752, 95% CI: 1.267 to 5.978, p = 0.011) respectively in pre-menopausal women. By cons, BMI was not associated with DFS or OS in postmenopausal women. Conclusions: Overweight is an independent prognostic factor for OS and DFS at 5 years in all patients with triple-negative breast cancer, and menopausal status may be a mitigating factor. Premenopausal women with overweight are at greater risk of death and progression than women with normal weight. Once validated, these results should be considered in the development of prevention programs. Creative Commons Attribution License

  18. ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Clément Chevalier

    Full Text Available The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.

  19. Tuberculous mastitis simulating carcinoma of the breast in a young ...

    African Journals Online (AJOL)

    Tuberculous mastitis is an uncommon disease even in countries where tuberculosis is highly endemic. It typically presents a diagnostic challenge masquerading as carcinoma or other primary disease of the breast. We report the case of a young multiparous Nigerian woman who presented with a tender left breast lump and ...

  20. Carcinoma or Sarcoma of the Breast | Patnayak | Journal of Basic ...

    African Journals Online (AJOL)

    Carcinoma or Sarcoma of the Breast. ... She was a 62-year-old female who presented with complaint of pain and lump in left breast of 6 months duration. There was a discharging ulcer measuring 4 ×6 cm ... The IDC was estrogen and progesterone receptor negative and Human Epidermal Growth Factor -2 receptor positive.

  1. Prognostic role of adjuvant radiotherapy in triple-negative breast cancer : A historical cohort study

    NARCIS (Netherlands)

    Bhoo Pathy, Nirmala; Verkooijen, Helena M.|info:eu-repo/dai/nl/213707705; Wong, Fuh-Yong; Pignol, Jean-Philippe; Kwong, Ava; Tan, Ern-Yu; Taib, Nur Aishah; Nei, Wen-Long; Ho, Gwo-Fuang; Tan, Benita; Chan, Patrick; Lee, Soo-Chin; Hartman, Mikael; Yip, Cheng-Har; Dent, Rebecca

    2015-01-01

    The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N=1,138) were

  2. The prognostic value of tumour-stroma ratio in triple-negative breast cancer

    NARCIS (Netherlands)

    Moorman, A.M.; Vink, R.; Heijmans, H.J.; van der Palen, Jacobus Adrianus Maria; Kouwenhoven, E.A.

    2012-01-01

    Background Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome.

  3. Surgery and radiation therapy of triple-negative breast cancers: From biology to clinics

    NARCIS (Netherlands)

    Bernier, J.; Poortmans, P.M.P.

    2016-01-01

    Triple negative breast cancer refers to tumours lacking the expression of the three most used tumour markers, namely oestrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). These cancers are known to carry a more dismal prognosis than the other molecular

  4. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer.

    Science.gov (United States)

    Tolaney, Sara M; Tan, Sally; Guo, Hao; Barry, William; Van Allen, Eliezer; Wagle, Nikhil; Brock, Jane; Larrabee, Katherine; Paweletz, Cloud; Ivanova, Elena; Janne, Pasi; Overmoyer, Beth; Wright, John J; Shapiro, Geoffrey I; Winer, Eric P; Krop, Ian E

    2015-10-01

    MET expression and activation appear to be important for initiation and progression of triple-negative breast cancer. Tivantinib (ARQ 197) is an orally administered agent that targets MET, although recent preclinical data suggests the agent may have mechanisms of action that are independent of MET signaling. We conducted a phase 2 study of tivantinib monotherapy in patients with metastatic triple-negative breast cancer. Patients with metastatic triple-negative breast cancer who had received 1 to 3 prior lines of chemotherapy in the metastatic setting were enrolled into this two-stage, single arm phase 2 study. Treatment consisted of twice daily oral dosing of tivantinib (360 mg po bid) during a 21-day cycle. Patients underwent restaging scans at 6 weeks, and then every 9 weeks. Tumor biomarkers that might predict response to tivantinib were explored. 22 patients were enrolled. The overall response rate was 5 % (95 % CI 0-25 %) and the 6-month progression-free survival (PFS) was 5 % (95 % CI 0-25 %), with one patient achieving a partial response (PR). Toxicity was minimal with only 5 grade ≥3 adverse events (one grade 3 anemia, one grade 3 fatigue, and 3 patients with grade 3/4 neutropenia). This study represents the first evaluation of tivantinib for the treatment of metastatic triple-negative breast cancer. These results suggest that single agent tivantinib is well tolerated, but did not meet prespecified statistical targets for efficacy.

  5. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

    DEFF Research Database (Denmark)

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways...

  6. Efficacy of Vancomycin-based Continuous Triple Antibiotic Irrigation in Immediate, Implant-based Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Lisa M. Hunsicker, MD, FACS

    2017-12-01

    Conclusions:. Continuous breast irrigation with a vancomycin-based triple antibiotic solution is a safe and effective accompaniment for immediate implant reconstruction. Use of intramuscular anesthetic injection for postoperative pain control allows the elastomeric infusion pump to be available for local tissue antibiotic irrigation.

  7. ADAM-17: a novel therapeutic target for triple negative breast cancer.

    LENUS (Irish Health Repository)

    McGowan, P M

    2013-02-01

    Validated targeted therapy is currently unavailable for patients with invasive breast cancer negative for oestrogen receptors, progesterone receptors and HER2 [i.e., those with triple-negative (TN) disease]. ADAM-17 is a protease involved in the activations of several ligands that bind to and promotes intracellular signalling from the EGFR\\/HER family of receptors.

  8. High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma.

    Science.gov (United States)

    Li, Xiaoxian; Wei, Bo; Sonmez, Ceyda; Li, Zaibo; Peng, Limin

    2017-08-01

    This study is to address the significance of tumor budding (TB) in breast carcinoma. Totally 244 estrogen receptor-positive (ER+)/HER2-negative (HER2-) and 131 triple-negative breast carcinoma (TNBC) diagnosed from 2004 to 2014 were analyzed. TB (cluster of up to 5 tumor cells at the invasive front) was evaluated using five 200× high-power fields (HPF) at the hotspot. The highest TB (H-TB) in 1 HPF and average TB (A-TB) in 5 HPFs were correlated with lymph node and distant metastasis, lymphovascular invasion (LVI), local recurrence, overall survival (OS), and disease-free survival (DFS). In ER+/HER2- cancer, H-TB and A-TB were significantly associated with distant metastasis. In TNBC, H-TB was associated with distant metastasis by univariate but not multivariate analysis; H-TB and A-TB were associated with LVI and worse OS (all P < .05). TB is associated with poor prognosis in ER+/HER2- and TNBC cancer. Evaluation of H-TB may be sufficient in breast carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Clinical characteristics of triple negative breast cancer in Egyptian women: a hospital-based experience

    Directory of Open Access Journals (Sweden)

    Nivine Gado

    2016-06-01

    Full Text Available Purpose: Triple negative breast cancer (TNBC is an aggressive subtype of breast cancer with poor prognosis despite the high rates of response to chemotherapy. We aim to study the clinical features, factors influencing recurrence and survival outcomes of TNBC patients.Methods: We retrospectively studied the charts of patients with biopsy proven TNBC treated at The Clinical Oncology Department Ain-Shams University between 2009 and 2012.Results: One hundred and forty five patients fulfilled the eligibility criteria. The incidence of TNBC was 10.5% - 15% with a mean of 12% of all breast cancer patients. The follow-up duration ranged from six months to four years. The age range was 26 to 78 years. Infiltrating ductal carcinoma represented 93.1% of the pathologic types. 87% of patients were free of metastases (M0 at presentation. Clinical stages II and III represented 38 and 39.5% of the patients. 66% of patients had modified radical mastectomy. Following surgery, 77.5% of patients received adjuvant chemotherapy while 61% of the patients had adjuvant radiation therapy. Anthracyclines based chemotherapy was given to 52% of patients. Disease-free survival (DFS of the M0 patients at 20 and 30 months was 92% and 80% respectively. Relapse occurred in 23% of M0 patients. After a mean duration of DFS of 15.1 months, the most common sites of metastases for relapsed M0 patients were pulmonary (44.8%, bone (41.4%, and locoregional (13.8%. The median overall survival (ORS of patients was 18 months (1 - 45 months, whereas for the M1 group of patients the median ORS was 9 months (2 - 29 months.Conclusion: The incidence, pathological characteristics, and clinical behavior of TNBC were similar to what is mentioned in the literature. Adding taxanes to the chemotherapy protocols and using postoperative radiotherapy were both associated with a significant increase in the mean period of DFS, while did not significantly affect the ORS.

  10. Heterogeneity of triple-negative breast cancer: mammographic, US, and MR imaging features according to androgen receptor expression

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Min Sun; Song, Sung Eun; Kim, Won Hwa; Lee, Su Hyun; Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Park, So Yeon; Park, In-Ae [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Han, Wonshik; Noh, Dong-Young [Seoul National University College of Medicine, Department of Surgery, Seoul (Korea, Republic of)

    2014-09-16

    Our aim was to determine whether triple-negative breast cancers (TNBCs) with and without androgen receptor (AR) expression have distinguishing imaging features on mammography, breast ultrasound (US), and magnetic resonance (MR) imaging. AR expression was assessed immunohistochemically in 125 patients with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced radiologists blinded to clinicopathological findings reviewed all imaging studies in consensus using the BI-RADS lexicon. The imaging and pathological features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs. The presence of mammographic calcifications with or without a mass (p < 0.001), non-mass enhancement on MR imaging (p < 0.001), and masses with irregular shape or spiculated margins on US (p < 0.001 and p = 0.002) and MR imaging (p = 0.001 and p < 0.001) were significantly associated with AR-positive TNBC. Compared with AR-negative TNBC, AR-positive TNBC was more likely to have a ductal carcinoma in situ component (59.8 % vs. 90.9 %, p = 0.001) and low Ki-67 expression (30.4 % vs. 51.5 %, p = 0.030). AR-positive and AR-negative TNBCs have different imaging features, and certain imaging findings can be useful to predict AR status in TNBC. (orig.)

  11. Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Vera L Silva

    Full Text Available The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line- 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 -CPTASNTSC and 4T1pep2-EVQSSKFPAHVS were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy.

  12. Phototheranostics of CD44-positive cell populations in triple negative breast cancer

    OpenAIRE

    Jiefu Jin; Balaji Krishnamachary; Yelena Mironchik; Hisataka Kobayashi; Zaver M. Bhujwalla

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44high/CD24low, and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed...

  13. Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Anna Rzepecka-Stojko

    2015-05-01

    Full Text Available Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP and its derivative caffeic acid phenethyl ester (CAPE towards two triple-negative breast cancer (TNBC cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL−1 for MDA-MB-23 cells and 33.68 µg∙mL−1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

  14. Primary and metastatic lobular carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Harake, Marie D.J.; Maxwell, Anthony J.; Sukumar, Sathi A

    2001-08-01

    Invasive lobular carcinoma of the breast is the second most common type of primary breast cancer, accounting for 8-14% of cases, but is often difficult to diagnose early. It typically shows a diffuse pattern of infiltration within the breast, resulting in a variety of often subtle radiological appearances. A similar infiltrative pattern is seen in its metastatic form, with involvement of the gastrointestinal tract, peritoneum, retroperitoneum, bone marrow, meninges and uterus occurring more frequently than with the more common infiltrating ductal carcinoma of the breast. This pictorial essay illustrates the spectrum of radiological appearances which may be encountered with both primary and secondary lobular carcinoma. Harake, M.D.J., Maxwell, A.J. and Sukumar, S.A. (2001). Clinical Radiology 56, 621-630.

  15. Metastatic breast carcinoma in pleural fluid: Correlation of receptor and HER2 status with the primary carcinoma-a pilot study.

    Science.gov (United States)

    Francis, Issam M; Alath, Preeta; George, Sara S; Jaragh, Mohammed; Al Jassar, Ayesha; Kapila, Kusum

    2016-12-01

    Documenting the four molecular subtypes of breast carcinoma is significant as they determine response to therapy, disease free interval and survival. Our aim was to document the subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2): namely ER + PR+ HER2+; ER + PR + HER2-; ER-PR-HER2+; and ER-PR-HER2- in metastatic breast carcinoma in pleural fluid and compare them with their expression in the primary breast tumor. Over a period of 18 months, 13 cases of invasive breast carcinoma with metastases to the pleural cavity were studied for subtypes. ER, PR, and HER2 were determined by IHC in the primary breast tumor and the cell blocks of the pleural fluid with metastatic carcinoma. Age ranged from 33 to 75 years. The primary tumor was ER + PR + HER2+; ER + PR + HER2-; ER-PR-HER2+ and ER-PR-HER2- in 2,9,0 and two cases, respectively while the metastatic tumor in pleural fluid was ER + PR + HER2+; ER + PR + HER2-; ER-PR- HER2+ and ER-PR-HER2- in 6, 3, 3, and 1, respectively. In five cases there was complete correlation between the primary and metastatic tumor. In 7 cases with HER2- primary tumor the metastases was HER2+. One from ER + PR+ HER2- primary tumor showed triple negative expression in the metastasis. Determining the molecular subtype in metastatic breast carcinoma is of importance as it affects the management. In our series 63% of metastatic tumors to the pleural fluid became HER2 positive and would thus require appropriate therapy. Diagn. Cytopathol. 2016;44:980-986. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Prognostic protein markers for triple negative breast cancer

    NARCIS (Netherlands)

    A. Umar (Arzu); N.Q. Liu (Ning Qing); R.B.H. Braakman (René)

    2010-01-01

    textabstractBreast cancer is the most commonly diagnosed malignancy in women in the Western world, with 13,000 new patients each year in the Netherlands alone. Extensive research on gene expression profiling has shown that breast cancer is a mixture of biologically different disease entities,

  17. SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma

    Directory of Open Access Journals (Sweden)

    Dongquan Chen

    2015-01-01

    Full Text Available Breast cancer (BC is the second most common cancer diagnosed in American women and is also the second leading cause of cancer death in women. Research has focused heavily on BC metastasis. Multiple signaling pathways have been implicated in regulating BC metastasis. Our knowledge of regulation of BC metastasis is, however, far from complete. Identification of new factors during metastasis is an essential step towards future therapy. Our labs have focused on Semaphorin 6D (SEMA6D, which was implicated in immune responses, heart development, and neurogenesis. It will be interesting to know SEMA6D-related genomic expression profile and its implications in clinical outcome. In this study, we examined the public datasets of breast invasive carcinoma from The Cancer Genome Atlas (TCGA. We analyzed the expression of SEMA6D along with its related genes, their functions, pathways, and potential as copredictors for BC patients’ survival. We found 6-gene expression profile that can be used as such predictors. Our study provides evidences for the first time that breast invasive carcinoma may contain a subtype based on SEMA6D expression. The expression of SEMA6D gene may play an important role in promoting patient survival, especially among triple negative breast cancer patients.

  18. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Directory of Open Access Journals (Sweden)

    Alicja M Kmiecik

    Full Text Available It has been recently found that metallothionein-3 (MT3 enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001. Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC, nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  19. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Science.gov (United States)

    Kmiecik, Alicja M; Pula, Bartosz; Suchanski, Jaroslaw; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Owczarek, Tomasz; Kruczak, Anna; Ambicka, Aleksandra; Rys, Janusz; Ugorski, Maciej; Podhorska-Okolow, Marzena; Dziegiel, Piotr

    2015-01-01

    It has been recently found that metallothionein-3 (MT3) enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001). Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC), nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  20. Reversing Anoikis Resistance in Triple-Negative Breast Cancer

    Science.gov (United States)

    2015-10-01

    hepatocellular carcinoma after curative resection. Cancer. 2012;118:2708-17. Epub 2011/10/13. 38. Liu JJ, Shen R, Chen L, et al. Piwil2 is expressed ...200c suppresses translation of these transcripts inappropriately expressed by carcinomas to facilitate anoikis resistance AND alters splicing events...induces apoptosis by shuttling proteins to the nucleus. The full-length transcript encodes a tumor suppressor motor protein whose loss of expression has

  1. Metaplastic Carcinoma of the Left Breast with Extensive Chondroid Differentiation

    Directory of Open Access Journals (Sweden)

    Dhiraj B Nikumbh,

    2011-01-01

    Full Text Available Metaplastic breast carcinoma is very rare neoplasm which contains mixture of carcinomatous (epithelial and sarcomatous (mesenchymal elements in variable proportion. Metaplastic carcinoma with chondroid differentiation is even rarer. We report a case of metaplastic carcinoma with extensive chondroid differentiation as there is paucity of information regarding pathological features and clinical outcomes for these rare tumors. Tumor had characteristic definite areas of classic infiltrating duct carcinoma with abundant chondromyxoid matrix, focal areas of chondrosarcoma and cartilagenous metaplasia. Tumour cells were immunoreactive for S-100, ER, and PR. When pathologist encounter breast tumor with chondroid differentiation, careful gross sampling, histopathology and immunoreactivity for mesenchymal and epithelial component are most useful to differentiate metaplastic carcinoma from malignant phylloides tumors and malignant adenomyoepithelioma.

  2. Squamous cell carcinoma of the breast tissue: a case report

    OpenAIRE

    Rubens José Pereira; Wilson Garcia Pereira; Luiz Fernando Jubé Ribeiro; Rita de Cássia Alencar; Vera Saddi; Geraldo Silva Queiroz; Ruffo Freitas Júnior

    1999-01-01

    O carcinoma espinocelular do parênquima mamário é um tipo raro de neoplasia, representando menos de 1% de todos os carcinomas mamários. Esse trabalho relata a condução de um caso diagnosticado e tratado no Serviço de Ginecologia e Mama do Hospital Araújo Jorge/ACCG. São discutidos a apresentação clínica, o diagnóstico e o prognóstico destes tumores.Squamous cell carcinoma of the mammary tissue is a very rare neoplasm, representing less than 1% of all breast carcinomas. The present study repor...

  3. Breast metastases of gastric signet ring cell carcinoma: A differential diagnosis with primary breast signet ring cell carcinoma

    Directory of Open Access Journals (Sweden)

    Qureshi S

    2005-01-01

    Full Text Available Metastatic deposits within the breast may be difficult to distinguish from primary breast carcinoma. Radiological features and immunohistochemistry especially for steroid hormone receptors and expression of gross cystic disease fluid protein may be helpful in differentiating these two conditions. In this report, we present a case of signet ring cell stomach cancer with metastasis to the breast and discuss the differential diagnostic options.

  4. Combining phenotypic and proteomic approaches to identify membrane targets in a 'triple negative' breast cancer cell type.

    Science.gov (United States)

    Rust, Steven; Guillard, Sandrine; Sachsenmeier, Kris; Hay, Carl; Davidson, Max; Karlsson, Anders; Karlsson, Roger; Brand, Erin; Lowne, David; Elvin, John; Flynn, Matt; Kurosawa, Gene; Hollingsworth, Robert; Jermutus, Lutz; Minter, Ralph

    2013-02-13

    The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a 'triple negative' breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other 'triple negative' breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated using the anti-CD73 antibody, which bound other 'triple negative

  5. Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

    Directory of Open Access Journals (Sweden)

    Rust Steven

    2013-02-01

    Full Text Available Abstract Background The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a ‘triple negative’ breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. Methods The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other ‘triple negative’ breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Results All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated

  6. Identifying Triple-Negative Breast Cancer Using Background Parenchymal Enhancement Heterogeneity on Dynamic Contrast-Enhanced MRI: A Pilot Radiomics Study.

    Directory of Open Access Journals (Sweden)

    Jeff Wang

    Full Text Available To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE MRI at 3.0 Tesla in identifying "triple-negative" breast cancers.In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC using cross-validation.Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (p<0.01. Similar improvements were seen in nearly all subtype classification tasks undertaken. Notably, amongst the most discriminating features for predicting triple-negative cancers were textures of background parenchymal enhancement.Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype

  7. [Differential diagnosis of invasive ductal carcinoma versus invasive lobular carcinoma of breast].

    Science.gov (United States)

    Yin, Hong-Fang; Li, Ting; Zhang, Hong; Zhang, Shuang

    2009-10-01

    To study the diagnostic usefulness of immunohistochemical markers in distinguishing between invasive ductal carcinoma and invasive lobular carcinoma of breast. Twenty-four cases of grade I invasive ductal carcinoma, 12 cases of classic invasive lobular carcinoma and 14 cases of invasive carcinoma with mixed ductal and lobular features were retrieved from the archival files of Peking University First Hospital during the period from January, 1998 to December, 2001. Immunohistochemical study for E-cadherin, p120 catenin, epithelia membrane protein 1 (EMP1) and DVL1 was performed. The positivity rates for E-cadherin in grade I invasive ductal carcinoma and classic invasive lobular carcinoma were 83.3% (20/24) and 0, respectively (P invasive ductal carcinoma (membranous staining) and classic invasive lobular carcinoma (cytoplasmic staining). The positivity rates for EMP1 and DVL1 in gradeI invasive ductal carcinoma were 95.8% (23/24) and 54.2% (13/24), respectively; while those in classic invasive lobular carcinoma were 12 and 5 cases, respectively. E-cadherin and p120 catenin are useful immunomarkers for distinguishing between invasive ductal carcinoma and invasive lobular carcinoma. On the other hand, EMP1 and DVL1 are of limited value in this respect.

  8. A case of carcinoma of the male breast mimicking a mucinous carcinoma of the skin

    Directory of Open Access Journals (Sweden)

    Sumihisa Imakado

    2012-06-01

    Full Text Available The authors report a case of mucinous carcinoma of the male breast firstly diagnosed as a mucinous carcinoma of the skin. The immunohistochemical results of this tumor were as follows: cytokeratin7 (-, gross cystic disease fluid protein 15 (-, p63 (-, estrogen receptor (+, and progesterone receptor (+ for the primary nodule; cytokeratin7 (-, thyroid transcription factor-1 (-, gross cystic disease fluid protein 15 (-, p63 (-, cytokeratin8 (+, cytokeratin18 (+, and cytokeratin20 (+ for the recurrent nodule. The tumor cells had cytokeratin7 (-/ cytokeratin20 (+ phenotype and it was very unusual for mucinous carcinoma of the breast.

  9. The protective effect of longer duration of breastfeeding against pregnancy-associated triple negative breast cancer.

    Science.gov (United States)

    ElShamy, Wael M

    2016-08-16

    Parity associated breast cancer (PABC) often diagnosed within the 2-5 years after a full term pregnancy. PABC is usually present with more advanced, poorly differentiated, high-grade cancers that show shorter time to progression and often of the triple negative breast cancer (TNBC) subtype. Data from around the world show that pregnancy-associated TNBC is independently associated with poor survival, underscoring the impact of the pregnant breast microenvironment on the biology and consequently the prognosis of these tumors. Although it is not yet clear, a link between pregnancy-associated TNBCs and lack or shorter duration of breastfeeding (not pregnancy per se) has been proposed. Here, we present epidemiological and experimental evidence for the protective effect of longer duration of lactation against pregnancy-associated TNBCs, and propose a putative molecular mechanism for this protective effect and its effect in eliminating any potential TNBC precursors from the breast by the end of the natural breast involution.

  10. Targeting Histone Abnormality in Triple Negative Breast Cancer

    Science.gov (United States)

    2016-08-01

    Zawacki K, Podewils LJ, Cohen G and McCorkle R. Exercise manages fatigue during breast cancer treatment: a randomized controlled trial. Psycho...27249683. 301. Bhargava R, Davidson NE. "Take two"? The role of second opinions for breast biopsy specimens. Bmj . 2016;353:i3256, 2016. PMID: 27339037...deacetylase regulates muscle differentiation. Nature 2000; 408: 106–111. 18 Martin M, Kettmann R, Dequiedt F. Class IIa histone deacetylases: conducting

  11. Tubulolobular carcinoma of the breast: Clinical, mammographic and sonographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Guenhan-Bilgen, Isil [Ege University Hospital, Department of Radiology, Bornova, Izmir (Turkey)]. E-mail: isilbilgen@hotmail.com; Oktay, Aysenur [Ege University Hospital, Department of Radiology, Bornova, Izmir (Turkey)

    2006-12-15

    Purpose: To determine and quantitate radiologic characteristics of tubulolobular carcinoma of the breast and to report clinical and pathologic findings. Materials and methods: A retrospective review of records of 2872 women who received a diagnosis of breast carcinoma between January 1988 and January 2006 revealed 26 histopathologically proven tubulolobular carcinoma of the breast. Analysis included history; findings at physical examination, mammography, and sonography (US) at the time of diagnosis and in postoperative follow-up, and histopathological results. Results: At physical examination, palpable mass was present in 85% (n = 22) of the patients. The mammographic findings were mass in 17 (65%), asymmetric focal density in 2 (8%), architectural distortion in 2 (8%) and negative mammograms in 5 (19%) of the 26 patients. US depicted 25 masses in 24 patients, all of which were hypoechoic, with spiculated (n = 13) or microlobulated (n = 12) margins. The cancer was clinically occult in 12% (n = 3), mammographically occult in 19% (n = 5), and radiologically occult in 4% (n = 1) of the patients. Histologically, the mean size of the tumor was 1.7 cm and 18 (69%) patients were node negative. Conclusion: Tubulolobular carcinoma of the breast usually manifests clinically as a firm, immobile mass and mammographically as a spiculated or ill-defined, irregular, isodense mass without microcalcifications. Common findings on sonography include a homogeneously hypoechoic, spiculated or microlobulated mass with posterior acoustic shadowing or normal acoustic transmission. Tubulolobular carcinoma should be included in the differential diagnosis for breast masses with these imaging features.

  12. Functional screen of paracrine signals in breast carcinoma fibroblasts.

    Directory of Open Access Journals (Sweden)

    Gui Su

    Full Text Available Stromal fibroblasts actively participate in normal mammary gland homeostasis and in breast carcinoma growth and progression by secreting paracrine factors; however, little is known about the identity of paracrine mediators in individual patients. The purpose of this study was to characterize paracrine signaling pathways between breast carcinoma cells and breast carcinoma-associated fibroblasts (CAF or normal mammary fibroblasts (NF, respectively. CAF and NF were isolated from breast carcinoma tissue samples and adjacent normal mammary gland tissue of 28 patients. The fibroblasts were grown in 3D collagen gel co-culture with T47D human breast carcinoma cells and T47D cell growth was measured. CAF stimulated T47D cell growth to a significantly greater degree than NF. We detected a considerable inter-individual heterogeneity of paracrine interactions but identified FGF2, HB-EGF, heparanase-1 and SDF1 as factors that were consistently responsible for the activity of carcinoma-associated fibroblasts. CAF from low-grade but not high-grade carcinomas required insulin-like growth factor 1 and transforming growth factor beta 1 to stimulate carcinoma growth. Paradoxically, blocking of membrane-type 1 matrix metalloprotease stimulated T47D cell growth in co-culture with NF. The results were largely mirrored by treating the fibroblasts with siRNA oligonucleotides prior to co-culture, implicating the fibroblasts as principal production site for the secreted mediators. In summary, we identify a paracrine signaling network with inter-individual commonalities and differences. These findings have significant implications for the design of stroma-targeted therapies.

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

    Directory of Open Access Journals (Sweden)

    Vinayak W Patil

    2011-03-01

    Full Text Available Vinayak W Patil1, Rajeev Singhai1, Amit V Patil2, Prakash D Gurav21Department of Biochemistry, Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India; 2Department of Surgery, Government Medical College, Miraj, IndiaAbstract: The aim of our study was to analyze triple-negative (TN breast cancer, which is defined as being negative for the estrogen receptor (ER, the progesterone receptor (PgR, and the human epidermal growth factor receptor 2 (HER-2/neu and which represents a subset of breast cancer with different biologic behavior. We investigated the clinicopathological characteristics and prognostic indicators of lymph node-negative TN breast cancer. Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India, from May 2007 to October 2010. Clinicopathological variables and clinical outcomes were evaluated. Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (<35 years, P = 0.003 and a higher histopathologic and nuclear grade (P < 0.001. It also correlated with a molecular profile associated with biological aggressiveness: negative for Bcl-2 expression (P < 0.001, positive for the epidermal growth factor receptor (P = 0.003, and a high level of p53 (P < 0.001 and Ki-67 expression (P < 0.00. The relapse rates during the follow-up period (median 56.8 months were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (P = 0.004. Relapse-free survival (RFS was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer: 3.5-year RFS rate 85.5% versus 94.2%, respectively; P = 0.001. On multivariate analysis, young age, close resection margin, and triple negativity were independent predictors of shorter RFS. TN breast cancer had a higher relapse rate and more aggressive clinicopathological

  14. Screen-detected mucinous breast carcinoma: Potential for delayed diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Dhillon, R. [Department of Diagnostic and Interventional Imaging, Royal Perth Hospital, Perth, WA (Australia)]. E-mail: ravinder.dhillon@health.wa.gov.au; Depree, P. [Department of Diagnostic and Interventional Imaging, Royal Perth Hospital, Perth, WA (Australia); Metcalf, C. [Department of Anatomical Pathology, Royal Perth Hospital, Perth, WA (Australia); Wylie, E. [Department of Diagnostic and Interventional Imaging, Royal Perth Hospital, Perth, WA (Australia)

    2006-05-15

    AIM: To describe the imaging features of 34 screen-detected mucinous carcinomas lesions. MATERIALS AND METHODS: The BreastScreen Western Australia (WA) database between January 1991 and December 2003 was searched. During this period, 214,507 women were screened and 2745 cases of invasive carcinoma and 45 cases of mucinous carcinoma were recorded. Case notes, radiology films and pathology reports of patients with mucinous carcinoma were reviewed. Thirty-four radiologically detected pure mucinous carcinomas are described. RESULTS: Of the pure mucinous carcinomas, the average age at diagnosis was 65 years (range 48-82 years), which was higher than that of other women with breast cancer (average age 60 years) screened at BreastScreen WA. Characteristic mammographic features of mucinous carcinoma are well-circumscribed masses with lobulated margins (26/34). Only 39% (11/28) of tumours were detected at ultrasound, as the smaller lesions less than 15 mm in diameter were often isoechoic with normal fat. Where histological grade was reported at excision, most (25/26) were low to medium-grade tumours (Bloom, Richardson and Elston grade I and II). A significant number of lesions (13/34) were evident on the previous screening examination where they were misinterpreted as benign lesions. However, none of these cases had positive axillary lymph nodes at final diagnosis. CONCLUSION: Although mammographically benign appearances of mucinous carcinoma caused a delay in diagnosis in 38% of the present cases, mucinous breast carcinomas have a favourable prognosis, as they are often low-grade tumours and rarely metastasize. Delay in diagnosis for these tumours in a screening programme may not lead to a significant adverse outcome for most women.

  15. Gallbladder metastases from ductal papillary carcinoma of the breast.

    Science.gov (United States)

    Murguia, Eduardo; Quiroga, Daniel; Canteros, Geraldine; Sanmartino, Cesar; Barreiro, Mariano; Herrera, Jose

    2006-01-01

    Breast cancer occurs primarily in women aged 25 years or older. Breast carcinoma has the potential for widespread dissemination, such as metastasis to axillary lymph nodes, bone, lung, pleura, brain, and soft tissues. Liver, gastrointestinal, and biliary tract involvement are infrequent. We report a patient, a 62-year-old woman, with symptomatic cholelithiasis. The patient proceeded to laparoscopic cholecystectomy. She had a previous history of mastectomy with axillary lymphadenectomy, performed for a breast ductal papillary carcinoma, 10 years prior to the cholecystectomy. The gallbladder was hydropic; the wall was thickened, with a focal broad-based lesion on the mesenteric face of the body. Histopathological evaluation of the focal broad-based lesion of the gallbladder revealed poorly differentiated adenocarcinoma infiltration, without mucosal involvement. Subsequent immunohistochemical examination showed the lesion to be cytokeratin 7(CK7)-positive and cytokeratin 20 (CK20)-negative. Estrogen receptor (ER) and progesterone receptor (PgR) were positive. The final pathological diagnosis was breast ductal papillary carcinoma metastases to the gallbladder. Mammography of the other breast was normal. Computed tomography (CT) scan of the brain, chest, abdomen, and pelvis was performed, without any pathological findings. Bone Tc-99 scintigraphy was normal. Six months after the surgery positron emission tomography (PET) showed no evidence of metastatic disease. Two years after the surgery, the patient died, in the absence of recurrence. A literature review revealed only a few more cases of metastasic breast carcinoma to the gallbladder.

  16. Malpractice litigation involving patients with carcinoma of the breast.

    Science.gov (United States)

    Mitnick, J S; Vazquez, M F; Kronovet, S Z; Roses, D F

    1995-10-01

    We sought to evaluate recent trends in the United States of America regarding malpractice awards for patients with carcinoma of the breast. A retrospective review was performed of 118 cases of purported malpractice in the diagnosis and management of patients with carcinoma of the breast and related problems. The information was tabulated from Westlaw Transmission, a computerized database. Gynecologists were the specialists most often sued and accounted for 47 percent of the physicians involved in lawsuits. Radiologists were cited in only 13 percent of the cases. Health maintenance organizations (HMOs) were cited in 5 percent of the cases. The most common complaint was delay in diagnosis, made by a plaintiff who detected her own breast mass (52 percent). In 15 percent of the cases, the plaintiffs complained that a mammogram was not obtained, and 9 percent complained that other diagnostic tests, such as ultrasound or fine-needle aspiration biopsy, were not performed. The average delay in diagnosis was 14 months. The average award to plaintiffs with carcinoma of the breast was $691,449. The average plaintiff's age was 44 years. Most malpractice complaints related to carcinoma of the breast are instituted by women under the age of 50 years who identified the breast mass by themselves and were assumed by their physicians to have fibrocystic disease of the breast. Complaints can be expected to increase regarding failure to order further diagnostic tests, such as ultrasound or fine-needle aspiration biopsy, despite a negative mammogram. Complaints against HMOs are now also being made, citing failure to properly diagnose or treat patients with carcinoma of the breast.

  17. Bilateral multiple extraocular muscle metastasis from breast carcinoma

    Directory of Open Access Journals (Sweden)

    Ramesh Murthy

    2011-01-01

    Full Text Available We report a rare presentation of an initially misdiagnosed case of a pseudotumor, which on histopathology was diagnosed as bilateral breast metastases of lobular carcinoma involving multiple extraocular muscles. A 61-year-old lady presented with external ophthalmoplegia and diplopia. Incisional biopsy was performed using a lid crease approach and the patient received radiotherapy and hormonal therapy. Following prolonged hormonal therapy, complete remission was achieved, with improvement in ocular motility and resolution of diplopia, about 18 months after the initial presentation. Multiple extraocular muscle involvement by breast carcinoma metastasis is very rare and should be considered in the differential diagnosis, especially in patients with a prior history of breast carcinoma.

  18. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.

    Science.gov (United States)

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

    2011-09-09

    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. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. [Case of heterochronous triple urogenital cancer (renal cell carcinoma, bladder cancer, prostatic cancer)].

    Science.gov (United States)

    Okumura, Akiou; Tsuritani, Shinji; Takagawa, Kiyoshi; Fuse, Hideki

    2013-11-01

    We report a case of a 73-year-old male with heterochronous triple urogenital cancer. The patient was referred to our hospital because serum PSA was elevated (7.0 ng/ml) in 1998. Prostatic needle biopsy revealed prostatic cancer in the right lobe, and total prostatectomy was performed. The histopathological diagnosis was moderately differentiated adenocarcinoma (TlcNOMO). Non-muscle invasive bladder cancer (NMIBC) was detected during an examination for microhematuria in 2002. Transurethral resection of the bladder tumor (TURBT) procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). A right renal mass was detected incidentally on follow-up CT for bladder cancer in 2008. Renal enucleation was performed in 2009. The histopathological diagnosis was grade 2 clear cell renal cell carcinoma (pTlaNXMO). NMIBC was detected on follow-up urethrocystoscopy in 2011. The TURBT procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). On follow-up for urogenital cancer patients, it is important to investigate recurrence of the primary cancer and also heterochronous canceration of other urogenital organs.

  20. Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

    OpenAIRE

    Hyun-Jung Kim; Kyeongmee Park; Jung Yeon Kim; Guhyun Kang; Geumhee Gwak; Inseok Park

    2017-01-01

    Background Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. Methods A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were...

  1. Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee [Keimyung University, School of Medicine, Daegu (Korea, Republic of); Zeon, Seok Kil [Dept. of Nuclear Medicine, Bundang Jesaeng General Hospital, Sungnam (Korea, Republic of); Kim, Su Jin [Dept. of Anesthesiology and Pain Medicine, Dongguk University, School of Medicine, Gyeongju (Korea, Republic of)

    2015-03-15

    The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUV{sub max}) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV{sub max} of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUV{sub max} compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer.

  2. Triple-negative breast cancer: are we making headway at least?

    Science.gov (United States)

    Arnedos, Monica; Bihan, Celine; Delaloge, Suzette; Andre, Fabrice

    2012-07-01

    The so-called triple-negative breast cancer, as defined by tumors that lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression, has generated growing interest in recent years despite representing less than 20% of all breast cancers. These tumors constitute an important clinical challenge, as they do not respond to endocrine treatment and other targeted therapies. As a group they harbor an aggressive clinical phenotype with early development of visceral metastases and a poor long-term prognosis. While chemotherapy remains effective in triple-negative disease, research continues to further identify potential new targets based on phenotypical and molecular characteristics of these tumors. In this respect, the presence of a higher expression of different biomarkers including epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and Akt activation has led to a proliferation of clinical trials assessing the role of inhibitors to these pathways in triple-negative tumors. Moreover, the described overlap between triple-negative and basal-like tumors, and the similarities with tumors arising in the BRCA1 mutation carriers has offered potential therapeutic avenues for patients with these cancers including poly (ADP-ribose) polymerase inhibitors and a focus on a higher sensitivity to alkylating chemotherapy agents. Results from these trials have shown some benefit in small subgroups of patients, even in single-agent therapy, which reflects the heterogeneity of triple-negative breast cancer and highlights the need for a further subclassification of these types of tumors for better prognosis identification and treatment individualization.

  3. Pleomorphic lobular carcinoma in situ of the breast: clinicopathologic review of 47 cases

    Science.gov (United States)

    Khoury, Thaer; Karabakhtsian, Rouzan G.; Mattson, David; Yan, Li; Syriac, Susanna; Habib, Fadi; Liu, Song; Desouki, Mohamed Mokhtar

    2015-01-01

    Background Pleomorphic lobular carcinoma in situ (PLCIS) of the breast is a distinctive entity, and yet its behavior and management are unclear. The purpose of this study was to review a relatively large number of cases and to evaluate the risk of recurrence. Methods Cases of PLCIS (n=47) over a 12 year-period were reviewed. The clinical, radiologic and pathologic findings were recorded. Immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR) and HER2 were performed. Results Thirty-one patients had no concurrent or past history of breast cancer, six (19.4%) of which had local recurrence. All tumors (4 invasive carcinoma and two PLCIS) were ipsilateral. Younger age at presentation was a high risk factor for local recurrence with mean and range of 52.5 (44, 59) vs. 60.6 (40, 81) years (p=0.03). Three of 31 patients were treated with radiation therapy (RT), none of which developed local recurrence. PLCIS had an adverse ER/PR/HER2 molecular profile with at least 41.2% of the cases overexpressing HER2. Moreover, at least 11.7% of the cases were triple negative. Conclusions This study included the largest number of patients that had no past or concurrent history of breast cancer with the longest clinical follow-up, providing an insight to the management practices and risk of recurrence from PLCIS. PMID:24372322

  4. Her-2 positive mucinous carcinoma breast cancer, case report.

    Science.gov (United States)

    Garcia Hernandez, Irean; Canavati Marcos, Mauricio; Garza Montemayor, Margarita; Lopez Sotomayor, Dulce; Pineda Ochoa, Diana; Gomez Macias, Gabriela Sofia

    2017-12-26

    Mucinous carcinoma is a variant of invasive breast carcinomas that accounts for 2% of them and has a better prognosis in contrast to the non-specific invasive carcinoma. They regularly are positive for estrogen and progesterone receptors and, generally, they do not overexpress HER2. When HER2 is positive, the first line treatment is trastuzumab; although the resistance is 52-89% for the non-specific carcinoma, it has been described just once in mucinous carcinoma. A 48-year-old female presented with a lump in her right breast and after a biopsy, it was diagnosed as mucinous carcinoma in the core biopsy and surgical resection, with positive hormone receptors and HER2 positive (3+) in 100% of the tumor cells. She was treated with neoadjuvant chemotherapy based on trastuzumab and pertuzumab with no pathological response. There are few pure mucinous carcinomas positive for HER2. Mucinous carcinomas are positive for HER2 account for less than 5% of invasive ductal carcinoma. Furthermore, our case was resistance to chemotherapy. Most mucinous carcinomas test negative for HER2, so they usually would not be treated with trastuzumab, in this case because the expression of HER2 in the biopsies we initiated it. It's important to know that cases of mucinous carcinoma positive for HER2 exist and to be aware of the clinical problems that they may present: resistance to trastuzumab. Also, we need to understand the responsible mechanisms of this resistance and use immunohistochemistry for MUC which may predict it. Copyright © 2017. Published by Elsevier Ltd.

  5. MR imaging of medullary carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Tominaga, Junya [Department of Radiology, Tohoku Rohsai Hospital, 21-3-4 Dainohara Aoba-ku, Sendai 981-8563 (Japan)], E-mail: jrtomi@jf6.so-net.ne.jp; Hama, Hikaru [Department of Radiology, Tohoku Rohsai Hospital, 21-3-4 Dainohara Aoba-ku, Sendai 981-8563 (Japan); Kimura, Noriko [Department of Pathology, Japan National Hospital Organization, Hakodate Hospital, 16-18 Kawahara-cho Hakodate, Hokkaido 041-8512 (Japan); Takahashi, Shoki [Department of Diagnostic Radiology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan)

    2009-06-15

    Purpose: To examine the magnetic resonance imaging (MRI) findings of medullary carcinoma of the breast and to correlate them with histopathologic features. Materials and methods: Eight patients were retrospectively evaluated with pathologically confirmed medullary carcinoma of the breast. T1-weighted fat-saturated, T2-weighted fast spine echo, and gadolinium-enhanced fat-saturated fast spoiled gradient-echo images were obtained. Interpretation of the MRI findings was based on evaluation of the configuration, internal signal intensity, contrast enhancement, and type of the time-intensity curve. Results: Medullary carcinoma showed a lobular shape and a smooth margin, either homogenous or heterogeneous enhancement and delayed peripheral enhancement in the late phase on contrast-enhanced MRI, and either a plateau or washout type with rapid initial rise on the time-intensity curve of the dynamic study. Conclusion: Although the MRI findings showed a close relationship with histopathologic features of medullary carcinoma, it was difficult to differentiate medullary carcinoma from other histologic types of invasive breast carcinomas.

  6. Metaplastic breast carcinoma with osseous differentiation: A rare case report.

    Science.gov (United States)

    Salih, Abdulwahid M; Kakamad, F H; Saeed, Yadkar A; Muhialdeen, Aso S

    2017-01-01

    Metaplastic breast carcinoma (MBC) is a rare type of breast cancer. Osseous differentiation is a very rare subtype. Reporting this kind of case is important because its clinical course and line of management are poorly mentioned in the literatures. We present a very rare case of MBC with osseous differentiation. A 48-year-old female presented with painless hard mass of the left breast. Examination and investigations showed MBC with osseous differentiation. She was managed by operation with adjuvant chemotherapy. MBC with osseous differentiation is a very rare type of breast carcinoma presenting with hard mass and managed by mastectomy, axillary lymph node sampling and adjuvant chemotherapy. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. [Mixed breast carcinoma with melanocytic differentiation in a man].

    Science.gov (United States)

    Kallel, Rim; Bahri, Ibticem; Abid, Najla; Feki, Jihène; Mellouli, Manel; Ayadi, Lobna; Boudawara, Tahya

    2014-04-01

    Male breast cancer is rare; the lobular type is exceptional. Only one case of mixed ductal and lobular type is reported in the literature. This is the first report on a mixed ductal and lobular carcinoma with melanocytic differentiation in a man. The aim of our study is to describe the clinicopathological characteristics of this rare type of breast tumor and to discuss its histogenesis. A 63-year-old man presented with cutaneous ulceration of the left breast. Ultrasound of the breast revealed a solid hypoechoic lesion, 13 mm in diameter. Microscopic evaluation of the biopsy showed an invasive ductal carcinoma. The patient received three cycles of chemotherapy and lost of view. Then consulted for increasing of the tumor size reaching 3 cm. Histological examination of the mastectomy specimen showed a mixed ductal and lobular carcinoma with melanocytic differentiation, confirmed by the immunohistochemical study. The patient received adjuvant chemotherapy and the evolution was favorable with an average follow-up of 9 months. Breast carcinoma with melanocytic differentiation is extremely rare; only seven cases are reported in the literature and all occurs in females. Its histogenesis is unclear; tumors exhibiting this combination of cell types may occur as collision or composite tumors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer

    OpenAIRE

    Paret, Claudia; Simon, Petra; Vormbrock, Kirsten; Bender, Christian; K?lsch, Anne; Breitkreuz, Andrea; Yildiz, ?zlem; Omokoko, Tana; Hubich-Rau, Stefanie; Hartmann, Christoph; H?cker, Sabine; Wagner, Meike; Roldan, Diana Barea; Selmi, Abderaouf; T?reci, ?zlem

    2015-01-01

    Triple-negative breast cancer (TNBC) is a high medical need disease with limited treatment options. CD8+ T cell-mediated immunotherapy may represent an attractive approach to address TNBC. The objectives of this study were to assess the expression of CXorf61 in TNBCs and healthy tissues and to evaluate its capability to induce T cell responses. We show by transcriptional profiling of a broad comprehensive set of normal human tissue that CXorf61 expression is strictly restricted to testis. 53%...

  9. Targeting MUC1 mediated tumor stromal metabolic interaction in Triple negative Breast Cancer

    Science.gov (United States)

    2016-11-01

    AWARD NUMBER: W81XWH-13-1-0315 TITLE: Targeting MUC1-mediated tumor -stromal metabolic interaction in Triple- negative breast cancer PRINCIPAL...2013- 14 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0315 Targeting MUC1-mediated tumor -stromal metabolic...recurrence within 1-3 years and a high mortality rate [3]. Therefore, identifying factors that facilitate tumor growth and metastases have the

  10. Targeting MUC1-Mediated Tumor-Stromal Metabolic Interaction in Triple-Negative Breast Cancer

    Science.gov (United States)

    2016-11-01

    AWARD NUMBER: W81XWH-13-1-0315 TITLE: Targeting MUC1-mediated tumor -stromal metabolic interaction in Triple- negative breast cancer PRINCIPAL...2013- 14 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0315 Targeting MUC1-mediated tumor -stromal metabolic...recurrence within 1-3 years and a high mortality rate [3]. Therefore, identifying factors that facilitate tumor growth and metastases have the

  11. Synchronous papillary thyroid carcinoma and breast ductal carcinoma: A rare case report and literature review.

    Science.gov (United States)

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

    2017-02-01

    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). 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. 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.

  12. Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.

    Science.gov (United States)

    Gil Del Alcazar, Carlos R; Huh, Sung Jin; Ekram, Muhammad B; Trinh, Anne; Liu, Lin L; Beca, Francisco; Zi, Xiaoyuan; Kwak, Minsuk; Bergholtz, Helga; Su, Ying; Ding, Lina; Russnes, Hege G; Richardson, Andrea L; Babski, Kirsten; Min Hui Kim, Elizabeth; McDonnell, Charles H; Wagner, Jon; Rowberry, Ron; Freeman, Gordon J; Dillon, Deborah; Sorlie, Therese; Coussens, Lisa M; Garber, Judy E; Fan, Rong; Bobolis, Kristie; Allred, D Craig; Jeong, Joon; Park, So Yeon; Michor, Franziska; Polyak, Kornelia

    2017-10-01

    To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2+ breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047. ©2017 American Association for Cancer Research.

  13. Cytolytic T Lymphocytes in Organotypic Breast Carcinoma Culture

    Science.gov (United States)

    2004-10-01

    by the marked differences between the CTL generated in ML TC in vitro compared to the CTL under in vivo conditions, as suggested by studies conducted...1. Isolate T cells and tumor cells from fresh, uncultured breast carcinoma tissues, or tissues cultured in the reconstruct or MLTC. 2. Compare ...393: 75-91. 2. Black, M.M., and Barclay, T.H.C. 1975. Prognosis in breast cancer utilizing histologic characteristics of the primary tumor. Cancer

  14. Breast carcinoma with osteoclast-like giant cells

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Lauridsen, M C; Sørensen, Flemming Brandt

    2001-01-01

    Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the female breast. The clinical course, histological, immunohistochemical and ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast-like multinucleated giant cells (OMGCs) are reviewed and a new...... in the literature have shown that 86% of patients with these tumours are still alive after 5 years. Histologically, these tumours are invasive ductal carcinomas with OMGCs next to the neoplastic glands and within their lumen. Signs of recent and past haemorrhage are ubiquitously present in the highly vascularized...

  15. A STUDY OF LOCALLY ADVANCED CARCINOMA OF BREAST

    Directory of Open Access Journals (Sweden)

    Prabhakar Jenna

    2017-08-01

    Full Text Available BACKGROUND Worldwide, breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women. Locally advanced breast cancer constitutes more than 50-70% of the patients presenting for treatment has two common problems in treatment. Achieving local control and prolonging survival by preventing or delaying distant metastasis. Today, treatment of LABC requires a combination of systemic and local/regional therapies. The aim of the study is to study the clinicopathological presentation, age distribution and various modes of management of locally advanced breast carcinoma. Worldwide breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women. Locally advanced breast cancer constitutes more than 50-70% of the patients presenting treatment. MATERIALS AND METHODS The present study includes 50 patients who attended Department of General Surgery for a period of three years. RESULTS The patients were regularly followed up and at the end of the study 35 (70% of the patients were doing well. 4(8% of the patients developed distant metastasis and 3 (6% of the patients developing local recurrence. 8 (16% of the patients were lost follow up. CONCLUSION About half of the cases presenting with breast cancer are in locally advanced stages. Multimodality therapy is the effective treatment of locally advanced carcinoma of breast. Breast cancer management is a challenge and improvement in therapies are needed for disease-free interval and overall survival period.

  16. Identifying Triple-Negative Breast Cancer Using Background Parenchymal Enhancement Heterogeneity on Dynamic Contrast-Enhanced MRI: A Pilot Radiomics Study

    Science.gov (United States)

    Wang, Jeff; Kato, Fumi; Oyama-Manabe, Noriko; Li, Ruijiang; Cui, Yi; Tha, Khin Khin; Yamashita, Hiroko; Kudo, Kohsuke; Shirato, Hiroki

    2015-01-01

    Objectives To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE) MRI at 3.0 Tesla in identifying “triple-negative" breast cancers. Materials and Methods In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC) using cross-validation. Results Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (pcancers were textures of background parenchymal enhancement. Conclusions Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype. Prospective validation studies are warranted to confirm these findings and determine potential implications. PMID:26600392

  17. Deep Sequencing Reveals a MicroRNA Expression Signature in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Chang, Yao-Yin; Lai, Liang-Chuan; Tsai, Mong-Hsun; Chuang, Eric Y

    2018-01-01

    Deep sequencing is an advanced technology in genomic biology to detect the precise order of nucleotides in a strand of DNA/RNA molecule. The analysis of deep sequencing data also requires sophisticated knowledge in both computational software and bioinformatics. In this chapter, the procedures of deep sequencing analysis of microRNA (miRNA) transcriptome in triple-negative breast cancer and adjacent normal tissue are described in detail. As miRNAs are critical regulators of gene expression and many of them were previously reported to be associated with the malignant progression of human cancer, the analytical method that accurately identifies deregulated miRNAs in a specific type of cancer is thus important for the understanding of its tumor behavior. We obtained raw sequence reads of miRNA expression from 24 triple-negative breast cancers and 14 adjacent normal tissues using deep sequencing technology in this work. Expression data of miRNA reads were normalized with the quantile-quantile scaling method and were analyzed statistically. A miRNA expression signature composed of 25 differentially expressed miRNAs showed to be an effective classifier between triple-negative breast cancers and adjacent normal tissues in a hierarchical clustering analysis.

  18. Invasive lobular carcinoma of the male breast: A rare histology of an uncommon disease.

    Science.gov (United States)

    Upadhyay, Rituraj; Kumar, Pavnesh; Sharma, D N; Haresh, K P; Gupta, Subhash; Julka, P K; Rath, G K; Bhankar, Himani

    2016-03-01

    Male breast carcinoma is a rare malignancy comprising less than 1% of all breast cancers. It is a serious disease with most patients presenting in advanced stages. Infiltrating ductal carcinoma is the most common histology while lobular carcinoma represents less than 1% of all these tumors. We report a case of locally advanced lobular carcinoma of breast in a 60 year old male. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  19. Modeling vitamin D actions in triple negative/basal-like breast cancer.

    Science.gov (United States)

    LaPorta, Erika; Welsh, JoEllen

    2014-10-01

    Breast cancer is a heterogeneous disease with six molecularly defined subtypes, the most aggressive of which are triple negative breast cancers that lack expression of estrogen receptor (ER) and progesterone receptor (PR) and do not exhibit amplification of the growth factor receptor HER2. Triple negative breast cancers often exhibit basal-like gene signatures and are enriched for CD44+ cancer stem cells. In this report we have characterized the molecular actions of the VDR in a model of triple negative breast cancer. Estrogen independent, invasive mammary tumor cell lines established from wild-type (WT) and VDR knockout (VDRKO) mice were used to demonstrate that VDR is necessary for 1,25-dihydroxyvitamin D3 (1,25D) mediated anti-cancer actions in vitro and to identify novel targets of this receptor. Western blotting confirmed differential VDR expression and demonstrated the lack of ER, PR and Her2 in these cell lines. Re-introduction of human VDR (hVDR) into VDRKO cells restored the anti-proliferative actions of 1,25D. Genomic profiling demonstrated that 1,25D failed to alter gene expression in KO240 cells whereas major changes were observed in WT145 cells and in KO clones stably expressing hVDR (KO(hVDR) cells). With a 2-fold cutoff, 117 transcripts in WT145 cells and 197 transcripts in the KO(hVDR) clones were significantly altered by 1,25D. Thirty-five genes were found to be commonly regulated by 1,25D in all VDR-positive cell lines. Of these, we identified a cohort of four genes (Plau, Hbegf, Postn, Has2) that are known to drive breast cancer invasion and metastasis whose expression was markedly down regulated by 1,25D. These data support a model whereby 1,25D coordinately suppresses multiple proteins that are required for survival of triple-negative/basal-like breast cancer cells. Since studies have demonstrated a high prevalence of vitamin D deficiency in women with basal-like breast cancer, correction of vitamin D deficiency in these women represents a

  20. Overexpression of ETV4 protein in triple-negative breast cancer is associated with a higher risk of distant metastasis

    Directory of Open Access Journals (Sweden)

    Yuan ZY

    2014-09-01

    -overexpressed tumor had a significantly higher risk of developing distant metastasis (P<0.0001 and shorter overall survival and disease-free survival. Overexpression of ETV4 protein was an independent predictor of short disease-free survival of TNBC patients (P=0.021. Conclusion: Overexpression of ETV4 protein increases risk of developing distant metastasis and results in a poor prognosis for TNBC patients. Thus, ETV4 might be a novel target for developing an alternative therapeutic strategy for prevention of TNBC distant metastasis. Keywords: breast carcinoma, triple-negative, ETS translocation variant 4, ETV4, prognosis

  1. Cutaneous metastasis of breast adenoid cystic carcinoma to the scalp.

    Science.gov (United States)

    Little, Anthony J; Seline, Alison E; Swick, Brian L; Wanat, Karolyn A

    2016-08-01

    Adenoid cystic carcinoma (ACC) is a tumor that can be of primary cutaneous origin or secondary to metastatic disease, most commonly salivary origin. Aside from primary cutaneous and salivary types, ACC of the breast is a rare, more indolent variant. Cutaneous metastases secondary to breast ACC is exceedingly uncommon and not previously reported to our knowledge. We present the case of a 67-year-old woman who developed cutaneous metastasis from primary breast ACC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. An associated classification of triple negative breast cancer: the risk of relapse and the response to chemotherapy.

    Science.gov (United States)

    Zhang, Jing; Wang, Yahong; Yin, Quangui; Zhang, Wei; Zhang, Tongxian; Niu, Yun

    2013-01-01

    Triple negative breast cancer (TNBC) is heterogeneous and considered as an aggressive tumor. This study was to evaluate the associated classification and its correlations with prognosis and the response to chemotherapy in Chinese women. Four hundred and twenty-eight cases of invasive TNBC were involved in this study. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK5/6), Ki67 and p53 were analyzed by immunohistochemistry and compared with patient outcome, and its implications and chemotherapy response were evaluated in four subgroups: typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), non-specific invasive ductal carcinoma (IDC) and other types. The factors of tumor grade, tumor stage, lymph node status, EGFR/CK5/6 status and p53 labeling index were different among the groups. TMC tumors had the lowest rate of relapse (5.8%), while AMC, IDC and other types were associated with an increased risk of relapse (19.1%, 26.7% and 38.2% respectively). Many factors were risk predictors of relapse for TNBC and IDC, while only positive lymph node was for AMC. For MC tumors, adjunctive chemotherapy decreased the risk of relapse in lymph node positive subgroup (36.8% and 66.7%), while not significant in lymph node negative one (8.1% and 10.0%). The classification based on histologic and IHC findings may be a significant improvement in predicting outcome in TNBC. The different chemotherapy response in subgroups may contribute to guiding the treatment of TNBC.

  3. Health Disparities and Triple-Negative Breast Cancer in African American Women: A Review.

    Science.gov (United States)

    Newman, Lisa A; Kaljee, Linda M

    2017-05-01

    Variation in cancer incidence and outcome has well-documented correlations with racial/ethnic identity. In the United States, the possible genetic and ancestral hereditary explanations for these associations are confounded by socioeconomic, cultural, and lifestyle patterns. Differences in the breast cancer burden of African American compared with European/white American women represent one of the most notable examples of disparities in oncology related to racial/ethnic identity. Elucidating the source of these associations is imperative in achieving the promise of the national Precision Medicine Initiative. Population-based breast cancer mortality rates have been higher for African American compared with white American women since the early 1980s, largely reflecting declines in mortality that have been disproportionately experienced among white American patients and at least partly explained by the advent of endocrine therapy that is less effective in African American women because of the higher prevalence of estrogen receptor-negative disease. The increased risk of triple-negative breast cancer in African American women as well as western, sub-Saharan African women compared with white American, European, and east African women furthermore suggests that selected genetic components of geographically defined African ancestry are associated with hereditary susceptibility for specific patterns of mammary carcinogenesis. Disentangling health care access barriers, as well as reproductive, lifestyle, and dietary factors from genetic contributions to breast cancer disparities remains challenging. Epigenetics and experiences of societal inequality (allostatic load) increase the complexity of studying breast cancer risk related to racial/ethnic identity. Oncologic anthropology represents a transdisciplinary field of research that can combine the expertise of population geneticists, multispecialty oncologists, molecular epidemiologists, and behavioral scientists to eliminate

  4. Targeting histone abnormality in triple negative breast cancer

    Science.gov (United States)

    2017-08-01

    antibody, and bound LSD1 was examined by IB using anti-LSD1 antibody. IB with anti-FLAG was used to detect the levels of FLAG- tagged HDAC5 full-length...HDAC5 cells were cultured for 7 months in medium containing 500 ng/ml ICR191. ICR191 generates genomic instability and genetic variability, and has...Reagents and cell culture conditions MDA-MB-231, MDA-MB-468, MCF-7, T47D, HCC-202 and SK-BR-3 cell lines were obtained from the ATCC/NCI Breast

  5. Glycogen-rich clear cell carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Hatzinikolaou ML

    2008-04-01

    Full Text Available Abstract Background Glycogen-rich carcinoma of the breast is a rare histological subtype of breast cancer, usually reported to have poor prognosis. Case presentation We present the case of a 59-year-old woman who underwent a mastectomy for a 3.5 cm clinically palpable left breast carcinoma, originally diagnosed as fibroadenoma on a screening mammogram four years before presentation. Diagnosis of clear cell carcinoma was based on certain histological characteristics of the tumour and immunohistochemical analysis (PAS staining, keratins AE1/AE3, EMA, cytokeratin 7, cytokeratin 20, melanosomes, vimentin, Chromogranin, Synaptophysin, S-100, SMA. No lymph node metastasis was found and as the tumour was ER positive and PgR negative, patient was treated only with an aromatase inhibitor upfront and remains free of disease 48 months now since operation. Conclusion Glycogen-rich clear cell carcinoma of the breast is a rare tumor, its clinical behavior reported to be rather aggressive so far, might varies depending on special characteristics such as low grade and strongly positive ER expression

  6. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Suhane, Sonal [Metabolic Photonics Laboratory, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States); Berel, Dror [Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States); Ramanujan, V. Krishnan, E-mail: Ramanujanv@csmc.edu [Metabolic Photonics Laboratory, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States)

    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.

  7. Middle ear effusion from metastatic carcinoma of the breast | Okpala ...

    African Journals Online (AJOL)

    Carcinoma of the breast can metastasise to many organs. Metastasis to the temporal bone is rare and even when it does, it would usually spread to other parts of the body. This is a report of isolated metastasis to the temporal bone with middle ear effusion.

  8. Lymphatic mapping with intralesional tracer administration in breast carcinoma patients

    NARCIS (Netherlands)

    Doting, MHE; Jansen, L; Nieweg, OE; Piers, DA; Tiebosch, ATMG; Rutgers, EJT; Kroon, BBR; Peterse, JL; Olmos, RAV; de Vries, J; Schraffordt Koops, H.

    2000-01-01

    BACKGROUND. The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary

  9. BRCA1-like signature in triple negative breast cancer : Molecular and clinical characterization reveals subgroups with therapeutic potential

    NARCIS (Netherlands)

    Severson, Tesa M; Peeters, Justine; Majewski, Ian; Michaut, Magali; Bosma, Astrid; Schouten, Philip C; Chin, Suet-Feung; Pereira, Bernard; Goldgraben, Mae A; Bismeijer, Tycho; Kluin, Roelof J C; Muris, Jettie J F; Jirström, Karin; Kerkhoven, Ron M; Wessels, Lodewyk; Caldas, Carlos; Bernards, René; Simon, Iris M; Linn, S.C.

    2015-01-01

    Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern

  10. Poor prognosis of constitutive gamma-H2AX expressing triple-negative breast cancers is associated with telomere length

    NARCIS (Netherlands)

    Nagelkerke, A.P.; Kuijk, S.J. van; Martens, J.W.; Sweep, F.C.; Hoogerbrugge, N.; Bussink, J.; Span, P.N.

    2015-01-01

    AIM: Here, we set out to establish whether endogenous gamma-H2AX is a biomarker in triple-negative breast cancer. METHODS: We explored the association of gamma-H2AX with mutation status and sensitivity to 139 different anticancer drugs in up to 41 breast cancer cell lines. Further, we correlated

  11. Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    R Joseph Bender

    Full Text Available Triple negative breast cancers (TNBC are difficult to treat due to a lack of targets and heterogeneity. Inhibition of angiogenesis is a promising therapeutic strategy, but has had limited effectiveness so far in breast cancer. To quantify heterogeneity in angiogenesis-related gene expression in breast cancer, we focused on two families--VEGFs and semaphorins--that compete for neuropilin co-receptors on endothelial cells. We compiled microarray data for over 2,600 patient tumor samples and analyzed the expression of VEGF- and semaphorin-related ligands and receptors. We used principal component analysis to identify patterns of gene expression, and clustering to group samples according to these patterns. We used available survival data to determine whether these clusters had prognostic as well as therapeutic relevance. TNBC was highly associated with dysregulation of VEGF- and semaphorin-related genes; in particular, it appeared that expression of both VEGF and semaphorin genes were altered in a pro-angiogenesis direction. A pattern of high VEGFA expression with low expression of secreted semaphorins was associated with 60% of triple-negative breast tumors. While all TNBC groups demonstrated poor prognosis, this signature also correlated with lower 5-year survival rates in non-TNBC samples. A second TNBC pattern, including high VEGFC expression, was also identified. These pro-angiogenesis signatures may identify cancers that are more susceptible to VEGF inhibition.

  12. HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Sandeep N Shah

    Full Text Available Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1 gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231, Hs578T by reprogramming cancer cells to a stem-like state. Silencing HMGA1 expression in invasive, aggressive breast cancer cells dramatically halts cell growth and results in striking morphologic changes from mesenchymal-like, spindle-shaped cells to cuboidal, epithelial-like cells. Mesenchymal genes (Vimentin, Snail are repressed, while E-cadherin is induced in the knock-down cells. Silencing HMGA1 also blocks oncogenic properties, including proliferation, migration, invasion, and orthotopic tumorigenesis. Metastatic progression following mammary implantation is almost completely abrogated in the HMGA1 knock-down cells. Moreover, silencing HMGA1 inhibits the stem cell property of three-dimensional mammosphere formation, including primary, secondary, and tertiary spheres. In addition, knock-down of HMGA1 depletes cancer initiator/cancer stem cells and prevents tumorigenesis at limiting dilutions. We also discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy.

  13. Targeting the androgen receptor in triple-negative breast cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Mina A

    2017-09-01

    Full Text Available Alain Mina,1 Rachel Yoder,2 Priyanka Sharma1 1Division of Medical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Westwood, 2University of Kansas Cancer Center, Kansas City, KS, USA Abstract: Triple-negative breast cancer (TNBC is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies. Recent advances in our understanding of androgenic signaling in TNBC, along with the identification of interacting pathways, are allowing development of the next generation of clinical trials with AR inhibitors. As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition. Keywords: triple-negative breast cancer, androgen signaling, targeted therapy, biomarkers, prognosis 

  14. Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer.

    Science.gov (United States)

    Bender, R Joseph; Mac Gabhann, Feilim

    2013-01-01

    Triple negative breast cancers (TNBC) are difficult to treat due to a lack of targets and heterogeneity. Inhibition of angiogenesis is a promising therapeutic strategy, but has had limited effectiveness so far in breast cancer. To quantify heterogeneity in angiogenesis-related gene expression in breast cancer, we focused on two families--VEGFs and semaphorins--that compete for neuropilin co-receptors on endothelial cells. We compiled microarray data for over 2,600 patient tumor samples and analyzed the expression of VEGF- and semaphorin-related ligands and receptors. We used principal component analysis to identify patterns of gene expression, and clustering to group samples according to these patterns. We used available survival data to determine whether these clusters had prognostic as well as therapeutic relevance. TNBC was highly associated with dysregulation of VEGF- and semaphorin-related genes; in particular, it appeared that expression of both VEGF and semaphorin genes were altered in a pro-angiogenesis direction. A pattern of high VEGFA expression with low expression of secreted semaphorins was associated with 60% of triple-negative breast tumors. While all TNBC groups demonstrated poor prognosis, this signature also correlated with lower 5-year survival rates in non-TNBC samples. A second TNBC pattern, including high VEGFC expression, was also identified. These pro-angiogenesis signatures may identify cancers that are more susceptible to VEGF inhibition.

  15. Expert opinion: Reporting needle core biopsies of breast carcinomas.

    Science.gov (United States)

    Hoda, S A; Harigopal, M; Harris, G C; Pinder, S E; Lee, A H S; Ellis, I O

    2003-07-01

    Many breast carcinomas are now diagnosed in needle core biopsies, after either mammographic detection or symptomatic presentation. There is dispute, however, about the range of information that should be included in the diagnostic report of these small and possibly unrepresentative samples. Is it sufficient to simply report the presence of carcinoma, in situ or invasive? Or should the histopathologist give a more detailed report including features of prognostic and predictive significance? If so, what is the evidence that the further information is, first, of clinical benefit and, second, not unreliable because of sampling variability? To address the question "What should be included in reports of needle core biopsies of breast carcinomas?" contributions were invited from authors in the USA and the UK.

  16. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    Directory of Open Access Journals (Sweden)

    Mohamed Mokhtar Desouki

    2015-01-01

    Full Text Available Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.

  17. Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Franziska Pern

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive form of breast carcinoma with a poor prognosis. Recent evidence suggests that some patients with TNBC harbour germ-line mutations in DNA repair genes which may render their tumours susceptible to novel therapies such as treatment with PARP inhibitors. In the present study, we have investigated a hospital-based series of 40 German patients with TNBC for the presence of germ-line mutations in BRCA1, BRCA2, PALB2, and BRD7 genes. Microfluidic array PCR and next-generation sequencing was used for BRCA1 and BRCA2 analysis while conventional high-resolution melting and Sanger sequencing was applied to study the coding regions of PALB2 and BRD7, respectively. Truncating mutations in BRCA1 were found in six patients, and truncating mutations in BRCA2 and PALB2 were detected in one patient each, whereas no truncating mutation was identified in BRD7. One patient was a double heterozygote for the PALB2 mutation, c.758insT, and a BRCA1 mutation, c.927delA. Our results confirm in a hospital-based setting that a substantial proportion of German TNBC patients (17.5% harbour germ-line mutations in genes involved in homology-directed DNA repair, with a preponderance of BRCA1 mutations. Triple-negative breast cancer should be considered as an additional criterion for future genetic counselling and diagnostic sequencing.

  18. Secretory carcinoma in a 79-year-old woman: an exceptionally rare type of breast carcinoma

    Directory of Open Access Journals (Sweden)

    Nelson Montalvo

    2016-12-01

    Full Text Available Secretory breast carcinoma is an exceptionally rare mammary gland neoplasia described mainly in adult females and children of both sexes, and very rarely in the elderly. It has particular histopathological and immunohistochemical features and a favorable prognosis. We report the case of a 79-year-old Hispanic woman with a palpable breast mass. Currently, the patient is disease free after a follow- up period of 6 years without local recurrence or axillary lymph-nodes nor distant metastases.

  19. A New Gene Expression Signature for Triple-Negative Breast Cancer Using Frozen Fresh Tissue before Neoadjuvant Chemotherapy

    OpenAIRE

    Santuario-Facio, Sandra K.; Cardona-Huerta, Servando; Perez-Paramo, Yadira X; Trevino, Victor; Hernandez-Cabrera, Francisco; Rojas-Martinez, Augusto; Uscanga-Perales, Grecia; Martinez-Rodriguez, Jorge L; Martinez-Jacobo, Lizeth; Padilla-Rivas,Gerardo; Mu��oz-Maldonado, Gerardo; Gonzalez-Guerrero, Juan Francisco; Valero-Gomez, Javier; Vazquez-Guerrero, Ana L; Herminia G Martinez-Rodriguez

    2017-01-01

    Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer tumors. Comparisons between TNBC and non���triple-negative breast cancer (nTNBC) may help to differentiate key components involved in TNBC neoplasms. The purpose of the study was to analyze the expression profile of TNBC versus nTNBC tumors in a homogeneous population from northeastern Mexico. A prospective study of 50 patients (25 TNBC and 25 nTNBC) was conducted. Clinic parameters were equally distributed for TNB...

  20. Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review.

    Science.gov (United States)

    Shin, Young Duck; Lee, Seul Kee; Kim, Kyu Sun; Park, Mi Ja; Kim, Joo Heon; Yim, Hyun Sun; Choi, Young Jin

    2014-01-08

    There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.

  1. Pregnancy stimulates tumor angiogenesis in breast carcinoma.

    Science.gov (United States)

    Genin, Anne-Sophie; Antoine, Martine; Aractingi, Selim; Rouzier, Roman

    2014-01-01

    The mechanisms responsible for the poor prognosis of pregnancy-associated breast cancer (PABC) remain not well-understood. We studied angiogenesis and lymphangiogenesis as they are known prognostic factors in breast cancer. We conducted a case control study of breast cancer comparing women with and without PABC matched for age and histological parameters. Surgical specimen sections were immunostained with anti-CD31 for angiogenesis and anti-D2-40 for lymphangiogenesis, then analyzed using vessel density, ratio of the vascular area and the Chalkley count. Seventeen patients with PABC and 22 controls were included. Angiogenesis was significantly increased in tumor tissues, and tended to be higher in healthy breast tissues from the PABC group compared to controls. In contrast, no difference between the two groups was found concerning lymphangiogenesis both in tumor and healthy breast tissues. Pregnancy enhances angiogenesis in breast cancer. This phenomenon appears to explain the poor prognosis of PABC.

  2. Inhibition of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Feng [Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072 (China); Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yang, Yong, E-mail: yyang@houstonmethodist.org [Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Medicine, Weill Cornell Medical College, New York, NY 10065 (United States)

    2014-11-21

    Highlights: • Suppression of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin. • Repression of PKM2 affects the glycolysis and decreases ATP production. • Downregulation of PKM2 increases the intracellular accumulation of doxorubicin. • Inhibition of PKM2 enhances the antitumor efficacy of doxorubicin in vivo. - Abstract: Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, we examined the effects of combined treatment with doxorubicin and anti-PKM2 small interfering RNA (siRNA) on triple-negative breast cancer (TNBC). The suppression of PKM2 resulted in changes in glucose metabolism, leading to decreased synthesis of adenosine triphosphate (ATP). Reduced levels of ATP resulted in the intracellular accumulation of doxorubicin, consequently enhancing the therapeutic efficacy of this drug in several triple-negative breast cancer cell lines. Furthermore, the combined effect of PKM2 siRNA and doxorubicin was evaluated in an in vivo MDA-MB-231 orthotopic breast cancer model. The siRNA was systemically administered through a polyethylenimine (PEI)-based delivery system that has been extensively used. We demonstrate that the combination treatment showed superior anticancer efficacy as compared to doxorubicin alone. These findings suggest that targeting PKM2 can increase the efficacy of chemotherapy, potentially providing a new approach for improving the outcome of chemotherapy in patients with TNBC.

  3. [FDG-PET/CT in staging of breast carcinoma: use in tumour stage III and locoregional recurrent breast carcinoma].

    NARCIS (Netherlands)

    Bulten, B.F.; Haas, M.J. de; Rodenburg, C.J.; Ooijen, B. van; Baas, I.O.; Klerk, J.M. de

    2014-01-01

    In stage III breast carcinoma, metastasized disease needs to be determined. In the past, conventional imaging by liver ultrasound, chest X-ray and bone scintigraphy was the work-up of choice. Recently, FDG-PET/CT was found to have additional value, but clinicians are hesitant to introduce this

  4. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Rajeshwari Mehta

    Full Text Available Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines.In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight, when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin.These results suggest that Deguelin may have a significant therapeutic value for the treatment of TNBC patients.

  5. Metaplastic carcinoma of the breast with chondroid calcification: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byung Ki; Byun, Kyung Hwan; Chung, Soo Yun; Yi, Mi Gyung; Bae, Jong Yup; Chung, Chul Woon [College of Medicine, Pochon CHA Univ, Pochon (Korea, Republic of)

    2002-02-01

    Metaplastic carcinoma is a rare form of breast carcinoma in which a variety of metaplastic changes occur. Thses commonly involve squamous or spindle cells, but pure chondroid metaplasia is relatively uncommon. We report a case of metaplastic carcinoma of the breast which mainly involved chondroid metaplasia and in which chondroid calcifications were seen on mammograms.

  6. Clinical value of R-spondins in triple-negative and metaplastic breast cancers.

    Science.gov (United States)

    Coussy, F; Lallemand, F; Vacher, S; Schnitzler, A; Chemlali, W; Caly, M; Nicolas, A; Richon, S; Meseure, D; El Botty, R; De-Plater, L; Fuhrmann, L; Dubois, T; Roman-Roman, S; Dangles-Marie, V; Marangoni, E; Bièche, I

    2017-06-06

    RSPO ligands, activators of the Wnt/β-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC). Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT-PCR. The effect of RSPO on the Wnt/β-catenin pathway activity was determined by luciferase assay, western blotting, and qRT-PCR. The effect of RSPO2 inhibition on proliferation was determined by using RSPO2 siRNAs. The effect of IWR-1, an inhibitor of the Wnt/β-catenin pathway, was examined on the growth of an RSPO2-positive patient-derived xenograft (PDX) model of metaplastic triple-negative BC. We detected RSPO2 and RSPO4 overexpression levels in BC, particularly in triple-negative BC (TNBC), metaplastic BC, and triple-negative cell lines. Various mechanisms could account for this overexpression: presence of fusion transcripts involving RSPO, and amplification or hypomethylation of RSPO genes. Patients with RSPO2-overexpressing tumours have a poorer metastasis-free survival (P=3.6 × 10(-4)). RSPO2 and RSPO4 stimulate Wnt/β-catenin pathway activity. Inhibition of RSPO expression in a TN cell line inhibits cell growth, and IWR-1 significantly inhibits the growth of an RSPO2-overexpressing PDX. RSPO overexpression could therefore be a new prognostic biomarker and therapeutic target for TNBC.

  7. Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast

    Science.gov (United States)

    Buerger, H; Simon, R; Schäfer, K-L; Diallo, R; Littmann, R; Poremba, C; van Diest, P J; Dockhorn-Dworniczak, B; Böcker, W

    2000-01-01

    Aims—The mutual relation of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) of the breast, as accepted precursor lesions of invasive breast cancer, is controversial. Because they display genetic heterogeneity, it is not clear how genetically advanced these entities are and what causes the transition to an invasive carcinoma. Methods—Six cases of LCIS, four of them with associated lobular invasive carcinoma, four cases of intermediately differentiated DCIS with an associated invasive lobular carcinoma, and nine cases of intermediately and poorly differentiated DCIS with associated ductal invasive carcinoma were investigated by means of comparative genomic hybridisation (CGH) after microdissection and immunohistochemical staining of E-cadherin. Results—LCIS was characterised by a low average rate of copy number changes, no evidence of amplifications, and a high rate of gains and losses of chromosomal material at 1q and 16q, respectively. A high degree of genetic homology with well differentiated DCIS was obvious, as reported previously. The cases of intermediately differentiated DCIS with associated lobular invasive components and lobular differentiation revealed striking homologies, and a significant difference of E-cadherin expression. The comparison of preinvasive and invasive breast lesions, irrespective of differentiation within the same patient, revealed no specific alteration that might be associated with invasion. Genetic alterations seen in invasive carcinoma were not necessarily seen in the adjacent precursor lesions. Conclusions—These results provide strong evidence that invasive breast cancer is a disease with multiple cytogenetic subclones already present in preinvasive lesions. Moreover, specific CGH alterations associated with invasion were not observed. Furthermore, the close genetic association between well differentiated and a subgroup of intermediately differentiated DCIS and LCIS led to the hypothesis that LCIS and a

  8. 36 cases adenoid cystic carcinoma of the breast in China: Comparison with matched grade one invasive ductal carcinoma-not otherwise specified.

    Science.gov (United States)

    Wang, Shuling; Li, Weidong; Wang, Fang; Niu, Yun; Hao, Chunfang; Wang, Xu; He, Lihong; Tong, Zhongsheng

    2017-04-01

    The aim of this study was to investigate the clinicopathological characteristic of adenoid cystic carcinoma (ACC). The clininopathological features, along with relapse free survival(RFS) and overall survival(OS) of 36 patients with ACC were retrospectively investigated and compared with those of 108 grade 1 invasive ductal carcinoma not-otherwise-specified (G1-IDC-NOS) patients. Most cases of ACC were ER, PR and HER-2 negative which was classified as triple-negative subtype. Five cases were concomitant with other pathological types of cancer. Axillary lymph node dissection(ALND) was performed in 31 patients and 2 of them with lymph nodes metastasis. Two patients died of lung metastases at 46 and 116 months after the surgery respectively. Compared with G1-IDC-NOS, ACC showed lower Ki-67 index, less lymph nodes metastasis, lower P53 expression, and higher proportion in location of upper outer quadrant of breast. There was no difference of OS and RFS between ACC and G1-IDC-NOS. ACC of the breast was a rare disease with a good prognosis although most of them were classified as triple-negative subtype. And the value of axillary node dissection and adjuvant therapy needs to be further investigated. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. 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.

    Science.gov (United States)

    Lim, Seung Taek; Yu, Jong Han; Park, Heung Kyu; Moon, Byung In; Ko, Byung Kyun; Suh, Young Jin

    2014-03-13

    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. 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). 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. Similar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients.

  10. Hydrophobic Fractionation Enhances Novel Protein Detection by Mass Spectrometry in Triple Negative Breast Cancer.

    Science.gov (United States)

    Lu, Ming; Whitelegge, Julian P; Whelan, Stephen A; He, Jianbo; Saxton, Romaine E; Faull, Kym F; Chang, Helena R

    2010-01-22

    It is widely believed that discovery of specific, sensitive and reliable tumor biomarkers can improve the treatment of cancer. The goal of this study was to develop a novel fractionation protocol targeting hydrophobic proteins as possible cancer cell membrane biomarkers. Hydrophobic proteins of breast cancer tissues and cell lines were enriched by polymeric reverse phase columns. The retained proteins were eluted and digested for peptide identification by nano-liquid chromatography with tandem mass spectrometry using a hybrid linear ion-trap Orbitrap.Hundreds of proteins were identified from each of these three specimens: tumors, normal breast tissue, and breast cancer cell lines. Many of the identified proteins defined key cellular functions. Protein profiles of cancer and normal tissues from the same patient were systematically examined and compared. Stem cell markers were overexpressed in triple negative breast cancer (TNBC) compared with non-TNBC samples. Because breast cancer stem cells are known to be resistant to radiation and chemotherapy, and can be the source of metastasis frequently seen in patients with TNBC, our study may provide evidence of molecules promoting the aggressiveness of TNBC.The initial results obtained using a combination of hydrophobic fractionation and nano-LC mass spectrometry analysis of these proteins appear promising in the discovery of potential cancer biomarkers. When sufficiently refined, this approach may prove useful for early detection and better treatment of breast cancer.

  11. Hydrophobic Fractionation Enhances Novel Protein Detection by Mass Spectrometry in Triple Negative Breast Cancer

    Science.gov (United States)

    Lu, Ming; Whitelegge, Julian P.; Whelan, Stephen A.; He, Jianbo; Saxton, Romaine E.; Faull, Kym F.; Chang, Helena R.

    2010-01-01

    It is widely believed that discovery of specific, sensitive and reliable tumor biomarkers can improve the treatment of cancer. The goal of this study was to develop a novel fractionation protocol targeting hydrophobic proteins as possible cancer cell membrane biomarkers. Hydrophobic proteins of breast cancer tissues and cell lines were enriched by polymeric reverse phase columns. The retained proteins were eluted and digested for peptide identification by nano-liquid chromatography with tandem mass spectrometry using a hybrid linear ion-trap Orbitrap. Hundreds of proteins were identified from each of these three specimens: tumors, normal breast tissue, and breast cancer cell lines. Many of the identified proteins defined key cellular functions. Protein profiles of cancer and normal tissues from the same patient were systematically examined and compared. Stem cell markers were overexpressed in triple negative breast cancer (TNBC) compared with non-TNBC samples. Because breast cancer stem cells are known to be resistant to radiation and chemotherapy, and can be the source of metastasis frequently seen in patients with TNBC, our study may provide evidence of molecules promoting the aggressiveness of TNBC. The initial results obtained using a combination of hydrophobic fractionation and nano-LC mass spectrometry analysis of these proteins appear promising in the discovery of potential cancer biomarkers. When sufficiently refined, this approach may prove useful for early detection and better treatment of breast cancer. PMID:20596302

  12. Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Kim Dong-Wan

    2007-11-01

    Full Text Available Abstract Background Prognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy. Methods A total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67 by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters. Results Among the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative vs. 62.2% in non-triple negative, p = 0.012 and pathologic complete RR (17.0% in triple negative vs. 3.1% in non-triple negative, p = 0.005. However, relapse free survival (RFS and overall survival (OS were significantly shorter in triple negative breast cancer patients (p p = 0.021, respectively. Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, p = 0.044. Conclusion Several molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated

  13. Adenoid cystic carcinoma of the breast at Enugu Nigeria.

    Science.gov (United States)

    Njeze, G E

    2007-03-01

    (Adenoid cystic carcinoma (ACC) of the breast is a rare type of neoplasm that is histologically indistinguishable from other examples in other sites and generally has a good prognosis). To characterize the clinical and pathological features of ACC in our environment, as well as the treatment offered to our patients, a review of the clinical records of patients treated at the University of Nigeria Teaching Hospital Enugu was undertaken. Case notes of breast cancer patients stored in the medical records department were retrospectively reviewed with a view to studying those with ACC. Follow up on these patients were documented. Adenoid cystic carcinoma of the breast was diagnosed in 9 out of 222 patients treated for cancer of the breast, from 1995-2000. Patients aged 34-70 years were afflicted with this disease. A lump in the breast led to the initial suspicion of a tumor. Some of them had pain in the breast. Many of the patients came with advanced disease. Surgical treatment ranged from simple mastectomy to modified radical mastectomy with radiotherapy and chemotherapy in some patients. The disease is rare at Enugu but contrary to findings elsewhere, majority of our patients had advanced disease. Those with early disease appeared to have a good outcome.

  14. Carcinoma or Sarcoma of the Breast

    African Journals Online (AJOL)

    from exuberant scars, fibromatosis, and nodular fasciitis and, more infrequently, from myofibroblastomas, pseudoangiomatous stromal hyperplasia, and acute and chronic abscess with fat necrosis. Metaplastic carcinomas with significant atypia must be distinguished from malignant phyllodes tumor and primary or metastatic.

  15. Molecular pathology of breast apocrine carcinomas

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromova, I.; Gromov, P.

    2006-01-01

    , specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG...

  16. The coexistence of atypical intraductal hyperplasias with breast carcinoma.

    Science.gov (United States)

    Bogdan, F; Gîrniţă, L; Florescu, M; Simionescu, C; Crăiţoiu, S; Comănescu, V

    1998-01-01

    We present a study made during 4 years (1992-1996), which pursued the underlining of the atypical intraductal hiperplasias (A.I.D.H.) lesions, met isolated or in the association with mamar carcinoma. Our study included a 188 number of the breast tumors, among: in the 23 cases we established the existence of the modification by the A.I.D.H, type at the fibrocystics disease associated or not with the other benign diseases of the breast (fibroadenosis, intraductal papiloma) and in the 63 cases there were the modification by the AIDH associated with in situ or invasiv carcinoma. Epithelial hyperplasia is frequently associated with the fibrocystic changes, being included in the category of fibrocystic or proliferating modifications. The synonymous terms used for the epithelial hyperplasia are the hiperplazia ductala, or the epitelioza, or the papilomatosis The last two are suggested by the proliferation possibility (papillary or linear) of the epithelial or the mio-epithelial cells. Regardless of the microscopic aspect of the lesion, that should be acknowledged and treated as it is, due to the increased risk of the development of a carcinoma later on, and also due to the ratio of association between the modification and the mammary carcinoma. The risk of occurrence of subsequent carcinoma is augmented in the presence of the epithelial atipii and also increases in the presence of a mammary carcinoma at the relatives of the first rank (1.3). In this context, the importance of the differential diagnosis between the simple intraductal hyperplasia and the atypical one, the difficulty of differentiation from intraductal carcinoma in some cases, and finally the association with an increased risk of subsequent occurrence of carcinoma, constitute into sufficient arguments to consider this topic separately.

  17. X-ray and ultrasound semiotics of mucinous carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    K. A. Lesko

    2013-01-01

    Full Text Available The article describes the main epidemiological, clinical and morphological diagnostic features of one of the rare breast cancer form – mucinous carcinoma of the breast. Current scientific data are followed by the results of own research the 9-year period of research.Authors draw attention to the very complex radiology peculiarities of the mucinous carcinoma of the breast.

  18. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    DEFF Research Database (Denmark)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos

    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 can...

  19. Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway

    National Research Council Canada - National Science Library

    PAN, HONG; ZHOU, WENBIN; HE, WEI; LIU, XIAOAN; DING, QIANG; LING, LIJUN; ZHA, XIAOMING; WANG, SHUI

    2012-01-01

    Genistein (Gen) has been reported as a protective factor against breast cancer. However, the molecular mechanism by which Gen elicits its effects on triple-negative breast cancer cells has not been fully elucidated...

  20. MYB Labeling by Immunohistochemistry Is More Sensitive and Specific for Breast Adenoid Cystic Carcinoma than MYB Labeling by FISH.

    Science.gov (United States)

    Poling, Justin S; Yonescu, Raluca; Subhawong, Andrea P; Sharma, Rajni; Argani, Pedram; Ning, Yi; Cimino-Mathews, Ashley

    2017-07-01

    Breast adenoid cystic carcinoma (ACC) is a primary breast carcinoma that, like salivary gland ACC, displays the t(6;9) translocation resulting in the MYB-NFIB gene fusion and immunopositivity for MYB by immunohistochemistry (IHC). However, it is not well established whether MYB immunoreactivity or rearrangement can be used to support a diagnosis of ACC in a malignant basaloid or benign cribriform breast lesion. Whole sections of primary breast ACC (n=11), collagenous spherulosis (CS; n=7), and microglandular adenosis (MGA; n=5) and tissue microarrays containing 16 basal-like, triple-negative breast carcinomas (TNBC) were labeled for MYB by IHC and underwent MYB fluorescence in situ hybridization using a break-apart probe. Strong, diffuse nuclear MYB labeling was seen in 100% ACC compared with no cases of basal-like TNBC, CS, or MGA (P=0.0001). Any degree of nuclear MYB labeling was seen in 100% ACC compared with 54% of all other cases (P=0.007), with any labeling seen in 71% CS, 63% basal-like TNBC, and 0% MGA. MYB rearrangement was detected in 89% (8/9) of evaluable ACC compared with 4% (1/26) of all other evaluable cases (P=0.0001), with a rearrangement detected in 1 (7%; n=1/15) evaluable basal-like TNBC. Strong, diffuse nuclear labeling for MYB is more sensitive than MYB fluorescence in situ hybridization for breast ACC and can be used to support a diagnosis of ACC in a cribriform or basaloid lesion in the breast. However, weak and focal labeling should be interpreted with caution as it can be seen in other benign cribriform and malignant basaloid lesions.

  1. Triple-Negative Breast Cancer in Ghanaian Women: The Korle Bu Teaching Hospital Experience.

    Science.gov (United States)

    Der, Edmund M; Gyasi, Richard K; Tettey, Yao; Edusei, Lawrence; Bayor, Marcel T; Jiagge, Evelyn; Gyakobo, Mawuli; Merajver, Sofia D; Newman, Lisa A

    2015-01-01

    Breast cancers that have negative or extremely low expression of estrogen receptor and progesterone receptor and non-amplification of human epidermal growth factor receptor-2 (HER2)/neu are termed triple-negative breast cancer (TNBC). The majority of TNBC tumors belong to the biologically aggressive basal subtype, and they cannot be managed with targeted endocrine or anti-HER2/neu agents. In western, high resource environments, risk factors for TNBC include younger age at diagnosis and hereditary susceptibility. Women of African ancestry in the United States and in continental Africa have higher frequencies of TNBC, prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer survival disparities related to racial/ethnic identity. Efforts to document and confirm the breast cancer burden of continental Africa have been hampered by the limited availability of registry and immunohistochemistry resources. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa, and to compare the frequencies as well as risk factors for TNBC versus non-TNBC in this large referral tertiary hospital. The Korle Bu Teaching Hospital is affiliated with the University of Ghana and is located in Accra, the capital of Ghana. We conducted an institutional, Department of Pathology-based review of the breast cancer cases seen at this facility for the 2010 calendar year, and for which histopathologic specimens were available. The overall study population of 223 breast cancer cases had a median age of 52.4 years, and most had palpable tumors larger than 5 cm in diameter. More than half were TNBC (130; 58.3%). We observed similar age-specific frequencies, distribution of stage at diagnosis and tumor grade among cases of TNBC compared to cases of non-TNBC. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively younger age at diagnosis compared to

  2. TNF-α Gene Knockout in Triple Negative Breast Cancer Cell Line Induces Apoptosis

    Directory of Open Access Journals (Sweden)

    Valentina Pileczki

    2012-12-01

    Full Text Available Tumor necrosis factor alpha (TNF-α is a pro-inflammatory cytokine involved in the promotion and progression of cancer, including triple negative breast cancer cells. Thus, there is significant interest in understanding the molecular signaling pathways that connect TNF-α with the survival of tumor cells. In our experiments, we used as an in vitro model for triple negative breast cancer the cell line Hs578T. The purpose of this study is to determine the gene expression profiling of apoptotic signaling networks after blocking TNF-α formation by using specially designed siRNA molecules to target TNF-α messenger RNA. Knockdown of TNF-α gene was associated with cell proliferation inhibition and apoptosis, as observed by monitoring the cell index using the xCELLigence RTCA System and flow cytometry. PCR array technology was used to examine the transcript levels of 84 genes involved in apoptosis. 15 genes were found to be relevant after comparing the treated group with the untreated one of which 3 were down-regulated and 12 up-regulated. The down-regulated genes are all involved in cell survival, whereas the up-regulated ones are involved in and interact with pro-apoptotic pathways. The results described here indicate that the direct target of TNF-α in the Hs578T breast cancer cell line increases the level of certain pro-apoptotic factors that modulate different cellular networks that direct the cells towards death.

  3. Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

    Science.gov (United States)

    Jablonska, Karolina; Pula, Bartosz; Zemla, Agata; Owczarek, Tomasz; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Podhorska-Okolow, Marzena; Ugorski, Maciej; Dziegiel, Piotr

    2013-04-01

    In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  4. Elevated expression of squamous cell carcinoma antigen (SCCA is associated with human breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Joseph M Catanzaro

    Full Text Available Squamous cell carcinoma antigen (SCCA belongs to the serine protease inhibitor (Serpin family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360 and normal breast epithelium (n = 124. SCCA expression was scored on a tiered scale (0-3 independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in Grade I (0.3%, Grade II (2.5%, and Grade III (9.4% breast cancers (p<0.0001. Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005. No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124. SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR double-negative tumors (p = 0.0009. Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively. This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment.

  5. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2009-03-05

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  6. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2012-02-01

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  7. Molecular mechanism of anti-cancer activity of phycocyanin in triple-negative breast cancer cells.

    Science.gov (United States)

    Ravi, Mathangi; Tentu, Shilpa; Baskar, Ganga; Rohan Prasad, Surabhi; Raghavan, Swetha; Jayaprakash, Prajisha; Jeyakanthan, Jeyaraman; Rayala, Suresh K; Venkatraman, Ganesh

    2015-10-23

    Triple-negative breast cancers represent an important clinical challenge, as these cancers do not respond to conventional endocrine therapies or other available targeted agents. Phycocyanin (PC), a natural, water soluble and non-toxic molecule is shown to have potent anti-cancer property. In this study, we determined the efficacy of PC as an anti-neoplastic agent in vitro on a series of breast cancer cell lines. We studied effects of PC in inducing DNA damage and apoptosis through western blot and qPCR. Also, anti-metastatic and anti-angiogenic properties were studied by classic wound healing and vasculogenic mimicry assays. We found that triple negative MDA-MB-231 cells were most sensitive to PC (IC50 : 5.98 ± 0.95 μM) as compared to other cells. They also showed decreased cell proliferation and reduced colony formation ability upon treatment with PC. Profile of Cell cycle analysis showed that PC caused G1 arrest which could be attributed to decreased mRNA levels of Cyclin E and CDK-2 and increased p21 levels. Mechanistic studies revealed that PC induced apoptosis as evident by increase in percentage of annexin positive cells, increase in γ-H2AX levels, and by changing the Bcl-2/Bax ratio followed by release of cytochrome C and increased Caspase 9 levels. MDA MB 231 cells treated with PC resulted in decreased cell migration and increased cell adhesive property and also showed anti-angiogenic effects. We also observed that PC suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) production. All these biological effects of phycocyanin on MDA MB 231 cells could be attributed to decreased MAPK signaling pathway. We also observed that PC is non-toxic to non-malignant cells, platelets and RBC's. Taken together, these findings demonstrate, for the first time, that PC may be a promising anti-neoplastic agent for treatment of triple negative breast cancers.

  8. Primary neuroendocrine carcinoma of the breast: report of 2 cases and literature review

    Directory of Open Access Journals (Sweden)

    Fernando Collado-Mesa, MD

    2017-03-01

    Full Text Available Neuroendocrine tumors of the breast are very rare accounting for less than 0.1% of all breast cancers and less than 1% of all neuroendocrine tumors. Focal neuroendocrine differentiation can be found in different histologic types of breast carcinoma including in situ and invasive ductal or invasive lobular. However, primary neuroendocrine carcinoma of the breast requires the expression of neuroendocrine markers in more than 50% of the cell population, the presence of ductal carcinoma in situ, and the absence of clinical evidence of concurrent primary neuroendocrine carcinoma of any other organ. Reports discussing the imaging characteristics of this rare carcinoma in different breast imaging modalities are scarce. We present 2 cases of primary neuroendocrine carcinoma of the breast for which mammography, ultrasound, and magnetic resonance imaging findings and pathology findings are described. A review of the medical literature on this particular topic was performed, and the results are presented.

  9. Pleomorphic variant of lobular carcinoma breast: A rare case report with review of the literature

    Directory of Open Access Journals (Sweden)

    Amit Gupta

    2012-01-01

    Full Text Available Pleomorphic carcinoma is a poorly described entity whose phenotype is not well recognized as within the morphological spectrum of breast carcinoma. The purpose of this report is to describe the clinicopathological features of this tumour with review of the literature. We report a case of invasive pleomorphic lobular carcinoma with coexisting classic lobular carcinoma in situ.

  10. Adenoid cystic carcinoma of the breast, 20 years of experience in a single center with review of literature.

    Science.gov (United States)

    Treitl, Daniela; Radkani, Pejman; Rizer, Magda; El Hussein, Siba; Paramo, Juan C; Mesko, Thomas W

    2017-05-02

    Adenoid cystic carcinoma (ACC) of the breast is a rare type of breast cancer, which presents inconsistencies in the optimal management strategy. A retrospective review of prospectively collected data, spanning the last 20 years, was performed using the cancer registry database at our institution. Six patients were diagnosed with ACC of the breast, out of 5,813 total patients diagnosed with breast cancer (0.1%). Our identified patients had a median age of 66, all with the early stage cancer (Stage I/II). The average size of the breast lesion was 1.62 cm, and nodal status was negative for all cases. All patients had resection as primary therapy (partial or total mastectomy), with one patient also undergoing external beam radiation and tamoxifen hormonal therapy. Median follow-up was 85 months, with all patients being disease-free at last follow-up. ACC of the breast has an indolent course, despite triple negative status. Our study suggests that radiation may not be warranted and confirms the rarity of axillary node metastases, indicating that sentinel node excision may also not be necessary. Ultimately, the hope is that our findings along with the reviewed literature will aid in determining the most appropriate options for management of ACC of the breast.

  11. Amygdalin Regulates Apoptosis and Adhesion in Hs578T Triple-Negative Breast Cancer Cells.

    Science.gov (United States)

    Lee, Hye Min; Moon, Aree

    2016-01-01

    Amygdalin, D-mandelonitrile-β-D-glucoside-6-β-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin α5 may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.

  12. Acinic cell carcinoma of the breast: review of the literature.

    Science.gov (United States)

    Limite, G; Di Micco, R; Esposito, E; Sollazzo, V; Cervotti, M; Pettinato, G; Varone, V; Benassai, G; Amato, B; Pilone, V; Luglio, G; Vitiello, A; Hasani, A; Liccardo, F; Forestieri, P

    2014-01-01

    The breast and salivary gland tissue share embryologic and thus pathological similarities. Acinic cell carcinoma (ACC) is a typical tumor in salivary glands, but rarely arises in breast too. We reviewed 38 cases of mammary ACC reported in literature and our case, the first ACC born within a fibroadenoma. Data were collected by a research for the key words acinic cell carcinoma breast on Pubmed in March 2014, including a case treated in our department. All reviewed cases were compared for clinical approach and histological pattern. To date 23 articles presenting cases of ACC of the breast are reported in literature. We included in our review 38 cases previously described and one new case. The histological pattern was predominantly solid with a microglandular structure. All the tumor cells were cytologically characterized by monotonous round cells with a finely granular, weakly eosinophilic, or clearly vacuolated cytoplasm. The most of the cells were intensely stained with anti-lysozime, anti-amylase, anti-α1-chimotripsin, anti-EMA and anti-S100 protein antisera. Immunohistochemistry was also performed to point out: estrogen receptor (ER), progesterone receptor (PR), androgen receptors (AR), human epidermal growth factor receptor 2 overexpression (HER2/neu), E-cadherin (E-cad), cytokeratin-7 (CK7), gross cystic disease fluid protein 15 (GCDFP15), smooth muscle actin (SMA). ACC of the breast is a rare tumor, showing similarities with the salivary gland counterpart, above all in terms of good prognosis, and differences from the ordinary invasive breast carcinoma. Further investigations are needed to elucidate the true histogenesis and the correct treatment. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  13. TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple Negative Breast Cancer

    Science.gov (United States)

    2016-10-01

    protein phosphorylation levels with cellular oncogenic phenotypes, we observed a novel non-receptor tyrosine kinase, TNK2, to be hyperphosphorylated...phosphorylation is observed upon (R)-9bMS treatment (Figure 6A). Inhibition of TNK2 activation is also reflected in significant decrease in AKT Tyr176...Triple-negative breast cancer: a short review. American journal of clinical oncology . 2010;33(6):637-45. doi: 10.1097/COC.0b013e3181b8afcf. PubMed

  14. Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer.

    LENUS (Irish Health Repository)

    Gonzalez-Angulo, Ana M

    2011-03-01

    To investigate the incidence of germline and somatic BRCA1\\/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation. Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1\\/2 exons\\/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chi-square. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome.

  15. The expression of APE1 in triple-negative breast cancer and its effect on drug sensitivity of olaparib.

    Science.gov (United States)

    Chen, Tianran; Liu, Chuan; Lu, Heng; Yin, Mingzhen; Shao, Changjuan; Hu, Xiaoding; Wu, Jiaxue; Wang, Yajie

    2017-10-01

    Triple-negative breast cancer is a kind of breast cancer with poor prognosis and special biological behavior, which lacked endocrine therapy and targeted therapy. We investigate the effect of human APE1 (apurinic/apyrimidyl endonuclease 1), a rate-limiting enzyme of base excision repair, on the prognosis in triple-negative breast cancer and drug sensitivity of olaparib. The expression of APE1 was detected by immunohistochemistry in the triple-negative breast cancer tissues and its effect on survival of triple-negative breast cancer patients was followed. To find whether APE1 effect the drug sensitivity in triple-negative breast cancer cells, the APE1-knockout HCC1937 cell line (triple-negative breast cancer cell line) was established by CRISPR/Cas9 system. Then, we use the wild-type and knockout one to test the drug sensitivity of olaparib. The expression of APE1 in triple-negative breast cancer tissues was significantly higher than that in the adjacent tissues (85.6% vs 14.4%) and its expression was related to tumor size (p triple-negative breast cancer (overall survival, p = 0.01). In vitro assay, the half maximal inhibitory concentration of olaparib in HCC1937-APE1-KO was significantly increased (17.22 vs 91.85 μM) compared to the wild type. The growth curve showed that olaparib had a stronger lethality on HCC1937 compared to HCC1937- APE1-KO (p < 0.05 on day 3). HCC1937 resulted in more mitotic G2/M arrest and increased apoptosis rate after treatment with 40 μM of olaparib, while HCC1937-APE1-KO did not change significantly. When HCC1937 was treated with different concentrations of olaparib, it was found that APE1 expression decreased more significantly at 15 μM of olaparib was. In HCC1937-APE1-KO, the expression of endogenous poly (ADP-ribose) polymerase 1 was also less than that of HCC1937. These results suggested that the expression of APE1 was an important basis for the maintenance of poly (ADP-ribose) polymerase 1, and the deletion of APE1 may be

  16. Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

    Science.gov (United States)

    Kim, Hyun-Jung; Park, Kyeongmee; Kim, Jung Yeon; Kang, Guhyun; Gwak, Geumhee; Park, Inseok

    2017-01-01

    Background Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. Methods A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). Results The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast. PMID:28597867

  17. Invasive lobular carcinoma of the breast: morphology, biomarkers and 'omics.

    Science.gov (United States)

    McCart Reed, Amy E; Kutasovic, Jamie R; Lakhani, Sunil R; Simpson, Peter T

    2015-01-30

    Invasive lobular carcinoma of the breast is the most common 'special' morphological subtype of breast cancer, comprising up to 15% of all cases. Tumours are generally of a good prognostic phenotype, being low histological grade and low mitotic index, hormone receptor positive and HER2, p53 and basal marker negative, and with a generally good response to endocrine therapy. Despite this, clinicians face countless challenges in the diagnosis and long-term management of patients, as they encounter a tumour that can be difficult to detect through screening, elicits a very invasive nature, a propensity for widespread metastatic colonisation and, consequently, in some studies a worse long-term poor outcome compared with invasive carcinoma of no special type. Here we review the morphological and molecular features that underpin the disparate biological and clinical characteristics of this fascinating tumour type.

  18. Adenosine Stimulate Proliferation and Migration in Triple Negative Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Miriam Fernandez-Gallardo

    Full Text Available Emerging evidence suggests that the adenosine (Ado receptors may play crucial roles in tumor progression. Here, we show that Ado increases proliferation and migration in a triple negative breast cancer model, the MDA-MB 231 cell line. The use of specific agonists and antagonists evidenced that these effects depend on the activation of the A2B receptor, which then triggers an intracellular response mediated by the adenylate cyclase/PKA/cAMP signaling pathway. Ado also increases the expression of NaV1.5 channels, a potential biomarker in breast cancer. Together, these data suggest important roles of the A2B receptors and NaV1.5 channels in the Ado-induced increase in proliferation and migration of the MDA-MB 231 cells.

  19. Triple Negative Breast Cancers Have a Reduced Expression of DNA Repair Genes

    Science.gov (United States)

    Andreis, Daniele; Bertoni, Ramona; Giardini, Roberto; Fox, Stephen B.; Broggini, Massimo; Bottini, Alberto; Zanoni, Vanessa; Bazzola, Letizia; Foroni, Chiara; Generali, Daniele; Damia, Giovanna

    2013-01-01

    DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects. PMID:23825533

  20. Triple negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers indentification.

    Science.gov (United States)

    Guestini, Fouzia; McNamara, Keely May; Ishida, Takanori; Sasano, Hironobu

    2016-06-01

    Triple negative breast cancer (TNBC) is a heterogeneous clinicopathological entity constituting approximately 15 - 20% of all breast cancer (BC) patients. It shows high recurrence rate and poor prognosis. At this juncture, because of the lack of specific targeted therapies available and the development in patients of resistance to some therapeutic agents, clinical and translational settings have gained importance over the past decades. The development of novel, safe and effective alternatives for the treatment of TNBC are in high demand. Therefore, this review aims to summarize the state of the art of TNBC, its current therapies and potential therapeutic targets. In particular, focus is put on recent advances regarding the identification of emerging biomarkers as prognostic and/or predictive markers, including surrogate markers for molecular tumor subtyping and identifying potential responders to new therapies. Effective development of informative markers could constitute an important armamentarium tool for identifying appropriate therapies to challenge the aggressiveness of TNBC.

  1. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy.

    Science.gov (United States)

    Feng, Tingting; Cao, Wei; Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-I; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2017-01-03

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors.

  2. Bosutinib reduces the efficacy of Dasatinib in triple-negative breast cancer cell lines.

    Science.gov (United States)

    Tarpley, Mike; Abdissa, Temesgen T; Johnson, Gary L; Scott, John E

    2014-04-01

    Triple-negative breast cancer (TNBC) is an aggressive sub-type of breast cancer. Dasatinib and bosutinib are FDA-approved Src/Abl kinase inhibitor drugs. Dasatinib potently inhibits the proliferation of many TNBC cell lines. The cell viability/proliferation for a panel of 4 TNBC cell lines was measured by detection of cellular ATP levels and cell numbers were directly determined by automated cell counting. Bosutinib (≤1 μM) had little to no inhibitory activity on cell viability/proliferation, while dasatinib-alone generated potent IC50 values of bosutinib resulted in reduced efficacy of dasatinib in all four cell lines, with two of them displaying a dramatic loss of efficacy. Direct cell counting confirmed that bosutinib enhanced cell proliferation in the presence of dasatinib. Bosutinib potently reduced the in vitro anti-proliferative efficacy of dasatinib in TNBC cell lines. We, hereby, report on a novel drug-induced loss in dasatinib sensitivity.

  3. Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway

    Science.gov (United States)

    Fanale, Daniele; Perez, Alessandro; Castiglia, Marta; Incorvaia, Lorena; Listì, Angela; Rizzo, Sergio; Cicero, Giuseppe; Bazan, Viviana; Castorina, Sergio; Russo, Antonio

    2016-01-01

    Breast cancer is one of the most widespread carcinoma and one of the main causes of cancer-related death worldwide, especially in women aged between 35 and 75 years. Among the different subtypes, triple negative breast cancer (TNBC) is characterized by the total absence of the estrogen-receptor (ER) and progesteron-receptor (PR) expression as well as the lack of human epidermal growth factor receptor 2 (HER2) overexpression or gene amplification. These biological characteristics confer to TNBC a higher aggressiveness and relapse risk along with poorer prognosis compared to other subtypes. Indeed, 5-years survival rate is still low and almost all patients die, despite any adjuvant treatment which at moment represents the heading pharmacological approach. To date, several clinical trials have been designed to investigate the potential role of some molecular markers, such as VEGF, EGFR, Src and mTOR, for targeted treatments in TNBC. In fact, many inhibitors of the PI3K/AKT/mTOR pathway, frequently de-regulated in TNBC, are acquiring a growing interest and several inhibitors are in preclinical development or already in early phase clinical trials. In this Review, we investigated the role of the PI3K/AKT/mTOR pathway in TNBC patients, by summarizing the molecular features that led to the distinction of different histotypes of TNBC. Furthermore, we provided an overview of the inhibition mechanisms of the mTOR and PI3K/AKT signaling pathways, highlighting the importance of integrating biological and clinical data for the development of mTOR inhibitors in order to implement targeted therapies for TNBC patients. PMID:27474173

  4. Multifocal squamous cell carcinoma of the oesophagus following radiotherapy for bilateral breast carcinoma

    Science.gov (United States)

    Shousha, S; Fawcett, A; Luqmani, Y; Theodorou, N

    2001-01-01

    A 60 year old woman who presented with dysphagia and weight loss was found to have multiple foci of dysplasia and in situ and invasive squamous cell carcinoma scattered along the whole length of the oesophagus, with intervening areas of normal mucosa. The patient had a history of two breast carcinomas 19 and one year previously for which she had repeated radiotherapy. Several members of the patient's close family had histories of malignant disease. All oesophageal lesions and the more recent breast cancer showed positive immunostaining for p53 protein. p53 mutations, some involving different exons, were also detected in these lesions. No p53 immunostaining or mutations were detected in the normal oesophageal mucosa. The findings suggest an independent origin of the multiple dysplastic and neoplastic foci, which might have developed in a background of a field change, possibly related to the previous radiotherapy. The strong family history of malignant diseases raises the possibility that, in addition, genetic factors might have played a role in the development of the oesophageal disease. Key Words: oesophageal carcinomabreast carcinoma • p53 • radiotherapy PMID:11533082

  5. Invasive micropapillary carcinoma of the breast: MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyo Soon; Jeong, Seo In; Choi, You Ri; Kim, Jin Woong; Lee, Ji Shin; Park, Min Ho [Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Kuzmiak, Cherie M. [Department of Radiology, University of North Carolina, Chapel Hill (Korea, Republic of)

    2013-08-15

    To analyze the magnetic resonance (MR) imaging findings of invasive micropapillary carcinoma of the breast. MR images were retrospectively evaluated in 14 patients (age range: 37-67, mean age: 49 years) with pathologically confirmed invasive micropapillary carcinoma of the breast. The enhancement type (mass/non-mass), shape, margin, contrast enhancement, and time-intensity curve pattern on the dynamic study were correlated with the histopathologic features. Associated findings, such as edema, nipple change, skin change and enlarged axillary lymph nodes were also studied. The most common features of the masses were irregular shape (12 of 14 patients, 85.8%) and irregular or spiculated margin (11 of 14 patients, 78.7%). The contrast enhancement was heterogeneous in 11 patients (78.7%), rim enhancement in 2 cases (14.2%), and homogeneous in one patient (7.1%). The predominant kinetic pattern was rapid increase (14 of 14, 100%) in the initial phase and washout (11 of 14, 78.7%) in the delayed phase. Associated non-mass like enhancement was shown in 4 patients, representing ductal carcinoma in situ. MR imaging helped detect additional sites of cancer other than the index lesion in 3 patients (21.4%). Enlarged axillary lymphadenopathy was identified in 7 of the 14 patients (50%). Invasive micropapillary carcinoma appears as a mass with an irregular shape, irregular or spiculated margin and heterogeneous enhancement on MR imaging. Though these findings are not specific and are also observed with other breast malignancies, invasive micropapillary carcinoma frequently showed multiple lesions, accompanying non-mass enhancement and axillary lymph node enlargement.

  6. Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

    Science.gov (United States)

    Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

    2017-04-01

    We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  7. Regulation of in situ to invasive breast carcinoma transition

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Regulation of In Situ to Invasive Breast CarcinomaTransition

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. [Metaplastic carcinoma of the breast and the impact of the p63 and cytokeratin 5/6: experience of 40 patients].

    Science.gov (United States)

    Sherwell-Cabello, S; Maffuz-Aziz, A; Hernández-Hernández, B; Bautista-Piña, V; Labastida-Almendaro, S; Rodríguez-Cuevas, S

    2016-03-01

    Metaplasic carcinoma of the breast was initially described by Huvos in 1974. It is a rare and aggressive entity characterized by the presence of mesenchymal and epithelial components. To know the incidence and biologic behaviour of the metaplasic carcinoma of the breast at the Instituto de Enfermedades de la Mama, FUCAM, AC. Data on women diagnosed with metaplasic carcinoma of the breast between January 2005 and December 2014 was collected by retrospectively reviewing in FUCAM. Clinical, pathological and immunohistochemical characteristics were assessed. The five-year disease-free survival (DFS) and overall survival (OS) were evaluated. a total of 4198 patients have been diagnosed with breast cancer in our institution, 40 (0.95%) of them with metaplasic carcinoma. The median age of the patients was 46 years (27-73). 60% of the patients were diagnosed with an advanced clinical stage (III) and the triple-negative subtype was the most frequently found. A mean follow-up of 24 months showed rates of overall survival and disease-free survival of 80% and 69.9%, respectively. The presence of both, cytokeratins 5/6 and p63, seems to have a negative impact in local recurrence. this study demonstrates that metaplasic carcinoma is a rare and aggressive disease. Expression of both tumor cytokeratins was associated with a worse outcome.

  10. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  11. Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

    Science.gov (United States)

    Oliveira, N C S; Gomig, T H B; Milioli, H H; Cordeiro, F; Costa, G G; Urban, C A; Lima, R S; Cavalli, I J; Ribeiro, E M S F

    2016-04-04

    Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.

  12. Primary adenoid cystic carcinoma of the breast: Case report and review of the literature.

    Science.gov (United States)

    Naseer, M A; Mohammed, S S; Alyusuf, R; Al Marzooq, R; Das Majumdar, S K; Al Hammadi, A

    2013-01-01

    Adenoid cystic carcinoma of the breast is a very rare neoplasm. We report a case of adenoid cystic carcinoma of the right breast presented with painless lump in the upper outer quadrant managed with lumpectomy, axillary lymph node staging and adjuvant local external radiotherapy to the whole breast with simultaneous integrated boost to the site of primary disease using respiratory gated intensity modulated radiotherapy. The available literature is reviewed. Adenoid cystic cancer breast, mastectomy, adjuvant radiotherapy.

  13. Metastatic Signet Ring Cell Carcinoma to the Breast: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Joon Ho; Kim, Eun Kyung; Kwak, Jin Young; Kim, Min Jung; Moon, Hee Jung [Yonsei University College of Medicine, Seoul (Korea, Republic of); Yoon, Jung Hyun [CHA University, College of Medicine, Seongnam (Korea, Republic of)

    2011-09-15

    Metastasis of signet ring cell gastric carcinoma to the breast is extremely rare. The common clinical findings are redness, edematous skin and pain, and these findings are similar to those of inflammatory breast cancer. We describe here a case of metastatic signet ring cell gastric carcinoma to the bilateral breasts, and this presented as bilateral palpable breast lumps after the patient had undergone radical total gastrectomy two years previously

  14. Invasive ductal carcinoma of the breast in a 14-year-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joo Yeon; Kim, Yun Ju; Kim, Sung Hun; Kang, Bong Joo [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Department of Radiology, Seoul (Korea, Republic of); Song, Byung Joo [The Catholic University of Korea, Department of General Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2014-11-15

    Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer. (orig.)

  15. Primary lymphoma of the breast involving both axillae with bilateral breast carcinoma

    Directory of Open Access Journals (Sweden)

    Rubin Gary

    2008-05-01

    Full Text Available Abstract Background Primary Non-Hodgkin's Lymphoma (PHNL of the breast is a rare entity, while secondary involvement of the breast with diffuse disease of Non-Hodgkin's lymphoma (NHL is more common. However, PNHL is the most frequent haematopoietic tumour of the breast. Diagnostic criteria for PNHL of the breast are presence of technically adequate pathologic specimens, close association of mammary tissue and lymphomatous infiltrate, no prior diagnosis of an extarammamary lymphoma, and no evidence of concurrent widespread disease, except for ipsilateral axillary lymph nodes if concomitant with the primary lesion. Case presentation A 57-year-old woman was recalled because her screening mammograms revealed three separate lesions in her right breast and one in the left. Histology of the lesions confirmed lymphoma in one breast with ductal carcinoma in the other. Conclusion Most of reported cases in literature have been involving the right breast, and almost all the patients were females. NHLs of the breast typically present as unilateral mass; the frequency of bilateral disease at first presentation ranges from 5–25%. Our objective is to report a case of primary lymphoma of the breast involving both axillae with concomitant bilateral primary breast cancer which has not been reported yet to our best of knowledge in literature.

  16. Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Xu Zhiyuan [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Schlesinger, David [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Toulmin, Sushila [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Rich, Tyvin [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Sheehan, Jason, E-mail: jps2f@virginia.edu [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States)

    2012-11-01

    Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

  17. [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo.

    Science.gov (United States)

    Martin, Ana Carolina B M; Fuzer, Angelina M; Becceneri, Amanda B; da Silva, James Almada; Tomasin, Rebeka; Denoyer, Delphine; Kim, Soo-Hyun; McIntyre, Katherine A; Pearson, Helen B; Yeo, Belinda; Nagpal, Aadya; Ling, Xiawei; Selistre-de-Araújo, Heloisa S; Vieira, Paulo Cézar; Cominetti, Marcia R; Pouliot, Normand

    2017-09-22

    There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.

  18. Phototheranostics of CD44-positive cell populations in triple negative breast cancer.

    Science.gov (United States)

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M

    2016-06-15

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44(high)/CD24(low), and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.

  19. The potential role of nanotechnology in therapeutic approaches for triple negative breast cancer.

    Science.gov (United States)

    Johnson, Rebecca; Sabnis, Nirupama; McConathy, Walter J; Lacko, Andras G

    2013-01-01

    Triple Negative Breast Cancer, TNBC, a highly aggressive and metastatic type of breast cancer, is characterized by loss of expression of the estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression of the human epidermal growth factor receptor 2 (HER2). It is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. Unfortunately, TNBC patients do not benefit from current anti-HER2 or hormone positive targeted breast cancer treatments; consequently, these patients rely primarily on chemotherapy. However, the 5-year survival rate for woman with metastatic TNBC is less than 30%. As a result of ineffective treatments, TNBC tumors often progress to metastatic lesions in the brain and lung. Brain metastases of invasive breast cancer are associated with 1 and 2 year survival rate of 20% and <2% respectively. Because the only current systemic treatment for TNBC is chemotherapy, alternative targeted therapies are urgently needed to improve the prognosis for TNBC patients. This review is focused on opportunities for developing new approaches for filling the current void in an effective treatment for TNBC patients.

  20. The Potential Role of Nanotechnology in Therapeutic Approaches for Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Andras G. Lacko

    2013-06-01

    Full Text Available Triple Negative Breast Cancer, TNBC, a highly aggressive and metastatic type of breast cancer, is characterized by loss of expression of the estrogen receptor (ER, progesterone receptor (PR, and a lack of overexpression of the human epidermal growth factor receptor 2 (HER2. It is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. Unfortunately, TNBC patients do not benefit from current anti-HER2 or hormone positive targeted breast cancer treatments; consequently, these patients rely primarily on chemotherapy. However, the 5-year survival rate for woman with metastatic TNBC is less than 30%. As a result of ineffective treatments, TNBC tumors often progress to metastatic lesions in the brain and lung. Brain metastases of invasive breast cancer are associated with 1 and 2 year survival rate of 20% and <2% respectively. Because the only current systemic treatment for TNBC is chemotherapy, alternative targeted therapies are urgently needed to improve the prognosis for TNBC patients. This review is focused on opportunities for developing new approaches for filling the current void in an effective treatment for TNBC patients.

  1. Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    This study was carried out to compare quantitative histopathological estimates obtained in normal breast epithelium (N = 15), lobular carcinoma in situ (N = 29), ductal carcinoma in situ (N = 24), invasive lobular carcinoma (N = 39), and invasive ductal carcinoma (N = 71) of the female breast......, and invasive carcinomas. Overlaps were, however, evident among the groups. There were no significant differences between means of the quantitative variables obtained in carcinoma in situ of the ductal and the lobular type with or without accompanying invasive carcinoma (2p > or = 0.22). A close correlation......, and the nuclear volume fraction, Vv(nuc/tis). The vv(nuc), aH(nuc), and MI were, on average, larger in ductal than in lobular carcinomas (2p carcinomas (2p = 3.10(-4). Comparing estimates obtained in tumors of pure ductal carcinoma in situ (N = 11) with those...

  2. Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells.

    Directory of Open Access Journals (Sweden)

    Shuping Yin

    Full Text Available Women with triple negative breast cancer (TNBC have poor prognosis compared to other breast cancer subtypes. There were several reports indicating racial disparity in breast cancer outcomes between African American (AA and European American (EA women. For example, the mortality rates of AA breast cancer patients were three times higher than of EA patients, even though, the incidence is lower in AA women. Our in vitro studies indicate that cancer stem-like cells (CSCs derived from AA TNBC cell lines have significantly higher self-renewal potential (mammosphere formation than CSCs derived from EA cell lines. TNBC tumors express high levels of Myc compared to luminal A or HER2 expressing breast cancers. We studied the effects of c-Myc overexpression on CSCs and chemotherapy in AA, and EA derived TNBC cell line(s. Overexpression of c-Myc in AA derived MDA-MB-468 (Myc/MDA-468 cells resulted in a significant increase in CSCs and with minimal changes in epithelial-to-mesenchymal transition (EMT compared to the control group. In contrast, overexpression of c-Myc in EA derived MDA-MB-231(Myc/MDA-231 cells led to increased epithelial-to-mesenchymal transition (EMT, with a minimal increase in CSCs compared to the control group. Myc/MDA-468 cells were resistant to standard chemotherapeutic treatments such as iniparib (PARP inhibitor plus cisplatin, / iniparib, cisplatin, paclitaxel and docetaxel. However, Myc/MDA-231 cells, which showed EMT changes responded to iniparib with cisplatin, but were resistant to other drugs, such as iniparib, cisplatin, paclitaxel and docetaxel. Collectively, our results indicate that intrinsic differences in the tumor biology may contribute to the breast cancer disparities.

  3. Surgical treatment of intracystic carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Sato Kazuhiro

    2011-10-01

    Full Text Available Abstract Background Intracystic carcinoma of the breast is a type of breast cancer with favorable prognosis where cancer arises from the cystic wall. However, it is a relatively rare disease, and no general consensus has been reached on its definition, including pathogenesis, extramural invasion, and lymph node metastasis. Methods Six patients who underwent surgery at the Department of Surgery at Asahikawa Medical University are presented. In each patient, background factors, diagnosis, surgery, pathological diagnosis, and prognosis were investigated. Results Fine needle aspiration showed class V disease in three patients and class III disease in the other three, and lumpectomy was performed for class III patients. Three patients underwent breast-conserving surgery While extramural invasion was seen in three patients, lymph node metastasis was absent in all patients. Conclusion When it is difficult to diagnose intracystic carcinoma of the breast by fine needle aspiration, active lumpectomy is necessary. Because extramural invasion and lymph node metastasis have been reported, it is necessary to carefully determine the range of excision and rationally perform lymph node dissection, such as sentinel node biopsy.

  4. Primary infiltrating ductal carcinoma of the axillary breast with metastasis to the contralateral chest wall

    Directory of Open Access Journals (Sweden)

    Li-Min Sun

    2013-06-01

    Full Text Available Primary infiltrating ductal carcinoma of the axillary breast is rare and has a high frequency of lymph node (LN involvement. We report a woman with primary infiltrating ductal carcinoma arising from the right axillary breast with metastasis to the contralateral chest wall. Excisional biopsy of the left chest wall nodule and the right axillary mass was carried out and both showed invasive ductal carcinomas histologically. The lesion of the right axillary mass arose from the breast tissue, rather than the LN. Further surgery proved the right axillary LN metastasis. After further review, a primary infiltrating ductal carcinoma of the right axillary breast with metastasis to axillary LNs and contralateral chest wall was diagnosed. The patient also received chemotherapy and radiation and there was no evidence of tumor recurrence after treatment. The present report demonstrated a rare case with uncommon manifestation. Lesions of uncertain origin around the periphery of the breast should be suspected for breast carcinoma.

  5. Invasive lobular carcinoma of breast with synchronous colon metastasis

    Directory of Open Access Journals (Sweden)

    Zhu-Jun Loh

    2017-01-01

    Full Text Available Secondary colon malignancy is rare and has a nonspecific presentation. Breast cancer is the second most common malignancy that metastasizes to the gastrointestinal (GI tract. Here, we present the case of a 54-year-old woman diagnosed with breast cancer and synchronous colon metastasis through a positive result obtained from stool occult blood screening. Colonoscopy revealed a subepithelial tumor of the colon. Biopsy revealed metastatic cancer with positive cytokeratin and GATA-binding protein 3 staining, as well as negative caudal-type homeobox 2 staining. A palpable right breast mass with nipple retraction was found, and invasive lobular carcinoma (ILC was diagnosed. Multiple bone, left adrenal gland, para-aortic lymph node, and contralateral breast metastases were detected. Multimodality treatment involving systemic chemotherapy, hormone therapy, and modified radical mastectomy was applied. In our clinical experience, colon metastasis from breast cancer is rare and usually mimics primary colon cancer. High-alert speculation and aggressive biopsy for patients with abnormal GI bleeding are indicated for diagnosis. Patients with colon metastasis from ILC of the breast have a poor prognosis. Therefore, multimodality treatments should be applied to improve their prognosis.

  6. High expression of miR-214 is associated with a worse disease-specific survival of the triple-negative breast cancer patients.

    Science.gov (United States)

    Kalniete, Dagnija; Nakazawa-Miklaševiča, Miki; Štrumfa, Ilze; Āboliņš, Arnis; Irmejs, Arvīds; Gardovskis, Jānis; Miklaševičs, Edvīns

    2015-01-01

    Hereditary triple-negative breast cancer patients have better recurrence-free survival than triple-negative sporadic ones. High expression of some of the miRNAs is related to worse overall and disease-free survival of triple-negative breast cancer patients. The attempt to associate expression level of some miRNA in triple-negative hereditary and sporadic breast cancers to disease specific survival was performed in this study. Study group was made of 18 triple-negative breast cancer patients harboring the BRCA1 gene mutations and 32 triple-negative sporadic breast cancer patients. Quantitative amount of mir-10b, mir-21, mir-29a, mir-31, and mir-214 by real-time PCR was assessed. The disease-specific survival in relation of high and low levels of some of the miRNAs was analyzed using Log-rank (Mantel-Cox) test. MiR-214 showed significantly higher expression level in sporadic tissues than in hereditary ones (p = 0.0005). Triple-negative breast cancer patients with high level of miR-214 showed significantly worse disease-specific survival than patients with low level (p = 0.0314). Our finding suggests that miR-214 possibly could be used as a potential prognostic biomarker for triple-negative breast cancer patients.

  7. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma.

    Science.gov (United States)

    Yetkin, Gurkan; Celayir, Fevzi; Akgun, Ismail Ethem; Ucak, Ramazan

    2017-01-01

    A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.

  8. Invasive Lobular Carcinoma of the Breast: Appearance on Digital Breast Tomosynthesis.

    Science.gov (United States)

    Grubstein, Ahuva; Rapson, Yael; Morgenstern, Sara; Gadiel, Itai; Haboosheh, Amit; Yerushalmi, Rinat; Cohen, Maya

    2016-10-01

    The aim of this study was to characterize the signs of invasive lobular carcinoma of the breast on digital breast tomosynthesis (DBT) imaging. The study group included 23 women with pathologically proven invasive lobular carcinoma of the breast for whom both digital mammography (DM) and DBT images were available. The images were read jointly by 2 experienced breast radiologists. Findings were recorded according to the descriptors in the Breast Imaging and Reporting Data System lexicon and correlated with the detailed pathology results. In 21 of the 23 patients, the combination of DM and DBT yielded pathologic findings (91%). Architectural distortions or spiculations were demonstrated in 87% of cases. The addition of DBT to DM improved lesion detection by more clearly depicting both the lesion margins and architectural distortions. Only 2 lesions were occult by both DM and DBT, including 1 lesion in a peripheral location that was not incorporated in the standard mediolateral oblique and craniocaudal views. DBT improves the detection of invasive lobular carcinoma lesions by more clearly depicting architectural distortions and spiculations.

  9. The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

    OpenAIRE

    Liu, Chun-Yu; Huang, Tzu-Ting; Chu, Pei-Yi; Huang, Chun-Teng; Lee, Chia-Han; Wang, Wan-Lun; Lau, Ka-Yi; Tsai, Wen-Chun; Chao, Tzu-I; Su, Jung-Chen; Chen, Ming-Huang; Shiau, Chung-Wai; Tseng, Ling-Ming; Chen, Kuen-Feng

    2017-01-01

    Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-medi...

  10. Molecular phenotypes in triple negative breast cancer from African American patients suggest targets for therapy.

    Science.gov (United States)

    Lindner, Robert; Sullivan, Catherine; Offor, Onyinye; Lezon-Geyda, Kimberly; Halligan, Kyle; Fischbach, Neal; Shah, Mansi; Bossuyt, Veerle; Schulz, Vincent; Tuck, David P; Harris, Lyndsay N

    2013-01-01

    Triple negative breast cancer (TNBC) is characterized by high proliferation, poor differentiation and a poor prognosis due to high rates of recurrence. Despite lower overall incidence African American (AA) patients suffer from higher breast cancer mortality in part due to the higher proportion of TNBC cases among AA patients compared to European Americans (EA). It was recently shown that the clinical heterogeneity of TNBC is reflected by distinct transcriptional programs with distinct drug response profiles in preclinical models. In this study, gene expression profiling and immunohistochemistry were used to elucidate potential differences between TNBC tumors of EA and AA patients on a molecular level. In a retrospective cohort of 136 TNBC patients, a major transcriptional signature of proliferation was found to be significantly upregulated in samples of AA ethnicity. Furthermore, transcriptional profiles of AA tumors showed differential activation of insulin-like growth factor 1 (IGF1) and a signature of BRCA1 deficiency in this cohort. Using signatures derived from the meta-analysis of TNBC gene expression carried out by Lehmann et al., tumors from AA patients were more likely of basal-like subtypes whereas transcriptional features of many EA samples corresponded to mesenchymal-like or luminal androgen receptor driven subtypes. These results were validated in The Cancer Genome Atlas mRNA and protein expression data, again showing enrichment of a basal-like phenotype in AA tumors and mesenchymal subtypes in EA tumors. In addition, increased expression of VEGF-activated genes together with elevated microvessel area determined by the AQUA method suggest that AA patients exhibit higher tumor vascularization. This study confirms the existence of distinct transcriptional programs in triple negative breast cancer in two separate cohorts and that these programs differ by racial group. Differences in TNBC subtypes and levels of tumor angiogenesis in AA versus EA patients

  11. Molecular phenotypes in triple negative breast cancer from African American patients suggest targets for therapy.

    Directory of Open Access Journals (Sweden)

    Robert Lindner

    Full Text Available Triple negative breast cancer (TNBC is characterized by high proliferation, poor differentiation and a poor prognosis due to high rates of recurrence. Despite lower overall incidence African American (AA patients suffer from higher breast cancer mortality in part due to the higher proportion of TNBC cases among AA patients compared to European Americans (EA. It was recently shown that the clinical heterogeneity of TNBC is reflected by distinct transcriptional programs with distinct drug response profiles in preclinical models. In this study, gene expression profiling and immunohistochemistry were used to elucidate potential differences between TNBC tumors of EA and AA patients on a molecular level. In a retrospective cohort of 136 TNBC patients, a major transcriptional signature of proliferation was found to be significantly upregulated in samples of AA ethnicity. Furthermore, transcriptional profiles of AA tumors showed differential activation of insulin-like growth factor 1 (IGF1 and a signature of BRCA1 deficiency in this cohort. Using signatures derived from the meta-analysis of TNBC gene expression carried out by Lehmann et al., tumors from AA patients were more likely of basal-like subtypes whereas transcriptional features of many EA samples corresponded to mesenchymal-like or luminal androgen receptor driven subtypes. These results were validated in The Cancer Genome Atlas mRNA and protein expression data, again showing enrichment of a basal-like phenotype in AA tumors and mesenchymal subtypes in EA tumors. In addition, increased expression of VEGF-activated genes together with elevated microvessel area determined by the AQUA method suggest that AA patients exhibit higher tumor vascularization. This study confirms the existence of distinct transcriptional programs in triple negative breast cancer in two separate cohorts and that these programs differ by racial group. Differences in TNBC subtypes and levels of tumor angiogenesis in AA

  12. Prevalence of papillomaviruses, polyomaviruses, and herpesviruses in triple-negative and inflammatory breast tumors from algeria compared with other types of breast cancer tumors.

    Directory of Open Access Journals (Sweden)

    Marilys Corbex

    Full Text Available The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups.One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology.Viral DNA was found in 22 (17.9% of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type than non-IBC tumors (30% vs. 13%, p<0.04. Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009.Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative. While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings.

  13. Single- versus Triple-Drug Chemoembolization for Hepatocellular Carcinoma: Comparing Outcomes by Toxicity, Imaging Response, and Survival.

    Science.gov (United States)

    Mouli, Samdeep K; Hickey, Ryan; Thornburg, Bartley; Sato, Kent T; Desai, Kush; Gabr, Ahmed; Kallini, Joseph R; Niemeri, Halla; Kircher, Sheetal; Mulcahy, Mary F; Benson Iii, Al B; Gupta, Ramona; Salem, Riad; Lewandowski, Robert J

    2016-09-01

    To determine the efficacy of single- versus triple-drug chemoembolization for the treatment of hepatocellular carcinoma, as measured by toxicity, tumor response, time to progression (TTP), and overall survival (OS). A single-center retrospective review was performed on 337 patients who underwent chemoembolization over a 14-year period; 172 patients underwent triple-drug conventional transarterial chemoembolization, and 165 patients underwent single-agent doxorubicin chemoembolization. Imaging characteristics and clinical follow-up after conventional transarterial chemoembolization were evaluated to determine TTP. Imaging response was determined per World Health Organization and European Association for the Study of Liver criteria. OS from time of first chemoembolization was calculated. Median TTP was similar between groups: 7.9 months (95% confidence interval [CI], 7.1-9.4) and 6.8 months (95% CI, 4.6-8.6) for triple- and single-drug regimens, respectively (P > .05). For single-agent conventional transarterial chemoembolization, median OS varied significantly by Barcelona Clinic for Liver Cancer (BCLC) stage: A, 40.8 months; B, 36.4 months; C, 10.9 months (P < .01). Median OS for triple-drug therapy also varied significantly by BCLC: A, 28.9 months; B, 18.1 months; C, 9.0 months (P < .01). Single-drug conventional transarterial chemoembolization demonstrated longer median OS compared with triple-drug therapy (P < .05) for BCLC A/B patients. Single-agent chemoembolization with doxorubicin and ethiodized oil demonstrates acceptable efficacy as measured by TTP and OS. Results compare favorably with traditional triple-drug therapy. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  14. NIPPLE AREOLA COMPLEX INVOLVEMENT IN EARLY AND LATE CARCINOMA BREAST

    Directory of Open Access Journals (Sweden)

    Firoz

    2015-08-01

    Full Text Available BACKGROUND : The last several decades h ave witnessed significant advances in the surgical management of carcinoma breast. Many have embraced breast conservation as the procedure of choice in carefully selected patients. It provides excellent cosmetic results side by side being oncologically saf e. Recent evidences have shown that involvement of nipple areola complex in breast cancer have been over estimated in the past based on older concept of occult tumor in the region of nipple and areola. Preservation of nipple and areola improves the quality of life and reduces the feeling of mutilation and thus is a logical step in conservative management of breast carcinoma. AIMS: (a To investigate the actual involvement of nipple areola complex clinically and histopathologically. (b To determine the asso ciated risk factors like site, size, distance, grading and lymph node status. MATERIALS AND METHOD S: This was a prospective study over a period of 2008 - 2011 carried out at Department of General Surgery of a tertiary care centre. Total number of patients i ncluded in the study was 54. All patients included in the study had undergone mastectomy for carcinoma of breast (excluding those patients who had clinical involvement of nipple areola complex. RESULTS: Among the patients of the study group majority of br east cancer occurred in age group 41 - 60 years (42.6% while incidence of nipple areola involvement was highest in age group 20 - 40 years. Majority of the patients detected with breast cancer were in stage II (44.4% while incidence of nipple areola involvem ent was highest in stage IV in our study. Mean largest dimension of the tumor was between 2 - 5cms while nipple areola involvement was found to be highest when the tumor is >5cms in largest dimension. Among the cases mean nipple tumor margin distance was bet ween 0 - 4cms while nipple areola involvement was found to be highest when the nipple tumor margin distance was < 2cms. CONCLUSION: It can

  15. Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

    Science.gov (United States)

    2017-11-15

    Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

  16. Reproductive factors and the risk of triple-negative breast cancer in white women and African-American women: a pooled analysis.

    Science.gov (United States)

    Ma, Huiyan; Ursin, Giske; Xu, Xinxin; Lee, Eunjung; Togawa, Kayo; Duan, Lei; Lu, Yani; Malone, Kathleen E; Marchbanks, Polly A; McDonald, Jill A; Simon, Michael S; Folger, Suzanne G; Sullivan-Halley, Jane; Deapen, Dennis M; Press, Michael F; Bernstein, Leslie

    2017-01-13

    Early age at menarche, nulliparity, late age at first completed pregnancy, and never having breastfed, are established breast cancer risk factors. However, among breast cancer subtypes, it remains unclear whether all of these are risk factors for triple-negative breast cancer (TNBC). We evaluated the associations of these reproductive factors with TNBC, in 2658 patients with breast cancer (including 554 with TNBC) and 2448 controls aged 20-64 years, who participated in one of the three population-based case-control studies: the Women's Contraceptive and Reproductive Experiences Study, the Women's Breast Carcinoma in situ Study, or the Women's Learning the Influence of Family and Environment Study. We used multivariable polychotomous unconditional logistic regression methods to conduct case-control comparisons among breast cancer subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression status. TNBC risk decreased with increasing duration of breastfeeding (P trend = 0.006), but age at menarche, age at first completed pregnancy, and nulliparity were not associated with risk of TNBC. Parous women who breastfed for at least one year had a 31% lower risk of TNBC than parous women who had never breastfed (odds ratio, OR = 0.69; 95% confidence interval, CI = 0.50-0.96). The association between breastfeeding and risk of TNBC was modified by age and race. Parous African-American women aged 20-44 years who breastfed for 6 months or longer had an 82% lower risk of TNBC than their counterparts who had never breastfed (OR = 0.18, 95% CI = 0.07-0.46). Our data indicate that breastfeeding decreases the risk of TNBC, especially for younger African-American women.

  17. Correlation of Physical Activities and Breast Cancer Characteristics: A Prospective Analysis with Special Focus on Triple Negative Breast Cancer.

    Science.gov (United States)

    Vallard, Alexis; Falk, Alexander Tuan; Antoine, Pascale; Guy, Jean-Baptiste; Guichard, Jean-Baptiste; Espenel, Sophie; Langrand-Escure, Julien; Trone, Jane-Chloé; Méry, Benoîte; Ben Mrad, Majed; Diao, Peng; Wang, Guoping; Roche, Frédéric; Bosacki, Claire; Chargari, Cyrus; Bourmaud, Aurélie; Magné, Nicolas

    2015-01-01

    Several studies have demonstrated that daily physical activity (PA) prevents the development of breast cancer. Our objective was to examine the relationship between PA and clinical and biological tumor characteristics in breast cancer patients in order to determine the impact of energy expenditure (EE) on tumor prognosis. We pooled data from two prospective studies, including a total of 121 breast cancer patients. The measure of PA was done using the self-completion Population Physical Activity Questionnaire, which was answered by each patient. Ten patients harbored triple negative (TN) tumors. The mean body mass index (BMI) in the general population and in patients with TN tumors was 24.3 and 25.6, respectively. The mean daily EE (DEE) was 10,266 kJ×24 h(-1) in the general population and 11,212 kJ×24 h(-1) in patients with TN tumors. In the whole population, there was an inverse statistical correlation between BMI and DEE, rest, low PA, and high PA (p=0.0002, p=0.003, pPA (p=0.041) and DEE (p=0.007). For TN tumors, there was no significant correlation between BMI and categories of EE. Lifestyle (weight regulation, PA) should be adapted and personalized according to biological, clinical, and epidemiological characteristics of the tumors. © 2015 S. Karger AG, Basel.

  18. Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Cecília P Popolin

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes (1 [Ru(SO4(dppb(bipy], (2 [Ru(CO3(dppb(bipy], (3 [Ru(C2O4(dppb(bipy] and (4 [Ru(CH3CO2(dppb(bipy]PF6 [where dppb = 1,4-bis(diphenylphosphinobutane and bipy = 2,2'-bipyridine], on proliferation of TNBC (MDA-MB-231, estrogen-dependent breast tumor cells (MCF-7 and a non-tumor breast cell line (MCF-10A. Complex (4 was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex (4 was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex (4 was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex (4 should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment.

  19. High Throughput Screening of Natural Phenolic Compounds Against Migration of Metastatic Triple-Negative Breast Cancer (TNBC) Cells

    OpenAIRE

    Nasrollahi, Samila

    2013-01-01

    In this report, we hypothesize that natural phenolic compounds may present a new class of chemotherapeutics against migration of metastatic triple-negative breast cancers (TNBC). In this project we will screen a small library of phenolic compounds to test this hypothesis, identify compounds that show efficacy against TNBC cell migration, and elucidate underlying molecular mechanisms.

  20. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    NARCIS (Netherlands)

    E.J. Sawyer (Elinor); R. Roylance (Rebecca); C. Petridis (Christos); R.H. Brook; S. Nowinski (Salpie); E. Papouli (Efterpi); O. Fletcher (Olivia); S. Pinder (Sarah); A. Hanby (Andrew); K. Kohut (Kelly); P. Gorman (Patricia); M. Caneppele (Michele); J. Peto (Julian); I. dos Santos Silva (Isabel); N. Johnson (Nichola); R. Swann (Ruth); M. Dwek (Miriam); K.-A. Perkins (Katherine-Anne); C. Gillett (Cheryl); R. Houlston (Richard); G. Ross (Gillian); P. de Ieso (Paolo); M.C. Southey (Melissa); J.L. Hopper (John); E. Provenzano (Elena); C. Apicella (Carmel); J. Wesseling (Jelle); S. Cornelissen (Sten); J.N. Keeman; P.A. Fasching (Peter); S.M. Jud (Sebastian); A.B. Ekici (Arif); M.W. Beckmann (Matthias); M. Kerin (Michael); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); P. Laurent-Puig (Pierre); P. Kerbrat (Pierre); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); R.L. Milne (Roger); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); J. Benítez (Javier); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); M. Lochmann (Magdalena); H. Brauch (Hiltrud); H.-P. Fischer; Y-D. Ko (Yon-Dschun); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); G. Chenevix-Trench (Georgia); D. Lambrechts (Diether); C. Weltens (Caroline); E. van Limbergen (Erik); S. Hatse (Sigrid); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); B. Bonnani (Bernardo); S. Volorio (Sara); G.G. Giles (Graham); G. Severi (Gianluca); L. Baglietto (Laura); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); V. Kristensen (Vessela); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); P. Devillee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); M. Kriege (Mieke); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); M.E. Sherman (Mark); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); C.H.M. van Deurzen (Carolien); J. Li (Jingmei); K. Czene (Kamila); M.K. Humphreys (Manjeet); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); M. Shah (Mitul); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); F.J. Couch (Fergus); B. Hallberg (Boubou); A. González-Neira (Anna); G. Pita (G.); M.R. Alonso (M Rosario); Y. Tessier (Yann); D. Vincent (Daniel); F. Bacot (Francois); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); A.M. Dunning (Alison); P. Hall (Per); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); M.K. Schmidt (Marjanka); I.P. Tomlinson (Ian); M. García-Closas (Montserrat)

    2014-01-01

    textabstractInvasive 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

  1. Increased risk of second malignancies after in situ breast carcinoma in a population-based registry

    NARCIS (Netherlands)

    I. Soerjomataram (Isabelle); M.W.J. Louwman (Marieke); M.J.C. van der Sangen (Maurice); R.M.H. Roumen (Rudi); J.W.W. Coebergh (Jan Willem)

    2006-01-01

    textabstractAmong 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972-2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma in situ patients exhibited a two-fold increased risk of second cancer (standardised incidence ratios (SIR): 2.1, 95% confidence

  2. Matrix-Producing Carcinoma of the Breast: A Case Report

    Directory of Open Access Journals (Sweden)

    Lorenzo Rossi

    2013-05-01

    Full Text Available Matrix-producing breast cancer (MPC is a subtype of metaplastic carcinoma of the breast. It is a very rare tumor, which constitutes less than 1% of all malignant mammary tumors. The origin of this tumor is still unclear: there are molecular studies that suggest an origin from myoepithelial cells, whereas other studies underline the neoplastic transformation of a multipotent stem cell. Even the differential diagnosis of MPC and other breast neoplasms (phyllodes tumors and real sarcomas of the breast is not always easy. In the literature, a certain chemoresistance has been demonstrated, and a standard treatment of this tumor does not exist at this time. We report the case of a 44-year-old, premenopausal, female patient with a 6-cm breast lump. Neither imaging nor fine needle aspiration biopsy was crucial in achieving a diagnosis. The patient underwent a simple mastectomy. In consideration of the negative lymph node status, the patient was not subjected to radiotherapy or adjuvant chemotherapy. Moreover, since the receptor status was negative, hormone therapy was not necessary. The patient has been disease free for 4 years now.

  3. Mammographic microcalcification in an autogenously reconstructed breast simulating recurrent carcinoma.

    Science.gov (United States)

    Hsu, Wayne; Sheen-Chen, Shyr-Ming; Eng, Hock-Liew; Ko, Sheung-Fat

    2008-01-01

    Breast cancer is a common cancer among women. The transverse rectus abdominis myocutaneous (TRAM) flap is a popular option because not only does it provide a breast with satisfactory bulk composed of autogenous tissue but it also provides an abdominal dermolipectomy to the patient. Fat necrosis remains a common problem following TRAM flap reconstruction, occurring in 10% to 36% of patients undergoing the procedure. A 44-year-old woman underwent a modified radical mastectomy followed by pedicled TRAM flap reconstruction after 5 months. Follow-up mammography 27 months after TRAM flap reconstruction showed a cluster of microcalcifications in the deep retroareolar area and recurrent breast carcinoma was highly suspected. Physical examination did not detect any abnormality of the reconstructed breast. Stereotactic hook localization was performed and an excisional biopsy was successfully done. The histological features of the resected specimens corresponded to fat necrosis change. Only with the awareness of the existence of such entity and careful follow-up can the occurrence of fat necrosis in TRAM flap reconstructed breasts be accurately detected and appropriately treated.

  4. Chk1 as a new therapeutic target in triple-negative breast cancer.

    Science.gov (United States)

    Albiges, Laurence; Goubar, Aïcha; Scott, Véronique; Vicier, Cécile; Lefèbvre, Céline; Alsafadi, Samar; Commo, Frédéric; Saghatchian, Mahasti; Lazar, Vladimir; Dessen, Philippe; Delaloge, Suzette; André, Fabrice; Quidville, Virginie

    2014-06-01

    Bioinformatics analyses of pathways and genes differentially expressed between malignant and benign lesions could allow discovering new therapeutic targets. Here, we identified Checkpoint kinase 1 (Chk1) as a potent therapeutic target in triple-negative breast cancer (TNBC). Differential gene expression between TNBC, other malignant and benign lesions was performed on two breast cancer datasets. Chk1 was targeted using RNA interference or chemical inhibitor in several TNBC cell lines. DNA repair pathway was identified as one mostly deregulated pathway in TNBC as compared to benign lesions. Chk1 was identified as candidate target among the 35 genes included in this pathway. Gene expression analysis revealed that Chk1 gene was significantly overexpressed in TNBC as compared to non-TNBC and benign lesions. Depletion of Chk1 protein expression induced a marked reduction of cell viability and led to mitotic catastrophe in TNBC cells. Chemical Chk1 inhibitor decreased survival in TNBC cells, and transcriptome analyze revealed a modulation of gene expression profile in response to Chk1 treatment. These findings suggest that Chk1 may represent a therapeutic target in TNBC, and provide a rationale to evaluate Chk1 inhibitors in breast cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Triple-Negative Breast Cancer: Next-Generation Sequencing for Target Identification.

    Science.gov (United States)

    Marotti, Jonathan D; de Abreu, Francine B; Wells, Wendy A; Tsongalis, Gregory J

    2017-10-01

    Presently, the ability to study disease at the most fundamental molecular level has led to a reclassification of human cancers into numerous subtypes that vary in disease progression and response to therapy. Similar to most solid tumors, breast cancer is a heterogeneous disease with considerable variation in histologic and biological features. Triple-negative breast cancer (TNBC) is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor-receptor 2 is not amplified or overexpressed. Data derived from highly complex molecular technologies, such as microarrays and next-generation sequencing, have identified gene expression and somatic mutation profile subsets of TNBC that reflect biological behavior more accurately and may lead to further effective therapeutic targets, better prognosis, and improved outcomes. Herein, we review the genomic findings of TNBC and discuss current efforts in precision medicine as they relate to TNBC. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Brachyury, a vaccine target, is overexpressed in triple-negative breast cancer.

    Science.gov (United States)

    Hamilton, Duane H; Roselli, Mario; Ferroni, Patrizia; Costarelli, Leopoldo; Cavaliere, Francesco; Taffuri, Mariateresa; Palena, Claudia; Guadagni, Fiorella

    2016-10-01

    Patients diagnosed with triple-negative breast cancer (TNBC) have a high rate of tumor metastasis and a poor prognosis. The treatment option for these patients is currently chemotherapy, which results in very low response rates. Strategies that exploit the immune system for the treatment of cancer have now shown the ability to improve survival in several tumor types. Identifying potential targets for immune therapeutic interventions is an important step in developing novel treatments for TNBC. In this study, in silico analysis of publicly available datasets and immunohistochemical analysis of primary and metastatic tumor biopsies from TNBC patients were conducted to evaluate the expression of the transcription factor brachyury, which is a driver of tumor metastasis and resistance and a target for cancer vaccine approaches. Analysis of breast cancer datasets demonstrated a predominant expression of brachyury mRNA in TNBC and in basal vs luminal or HER2 molecular breast cancer subtypes. At the protein level, variable levels of brachyury expression were detected both in primary and metastatic TNBC lesions. A strong association was observed between nuclear brachyury protein expression and the stage of disease, with nuclear brachyury being more predominant in metastatic vs primary tumors. Survival analysis also demonstrated an association between high levels of brachyury in the primary tumor and poor prognosis. Two brachyury-targeting cancer vaccines are currently undergoing clinical evaluation; the data presented here provide rationale for using brachyury-targeting immunotherapy approaches for the treatment of TNBC. © 2016 Society for Endocrinology.

  7. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer

    Science.gov (United States)

    Bhola, Neil E.; Balko, Justin M.; Dugger, Teresa C.; Kuba, María Gabriela; Sánchez, Violeta; Sanders, Melinda; Stanford, Jamie; Cook, Rebecca S.; Arteaga, Carlos L.

    2013-01-01

    After an initial response to chemotherapy, many patients with triple-negative breast cancer (TNBC) have recurrence of drug-resistant metastatic disease. Studies with TNBC cells suggest that chemotherapy-resistant populations of cancer stem-like cells (CSCs) with self-renewing and tumor-initiating capacities are responsible for these relapses. TGF-β has been shown to increase stem-like properties in human breast cancer cells. We analyzed RNA expression in matched pairs of primary breast cancer biopsies before and after chemotherapy. Biopsies after chemotherapy displayed increased RNA transcripts of genes associated with CSCs and TGF-β signaling. In TNBC cell lines and mouse xenografts, the chemotherapeutic drug paclitaxel increased autocrine TGF-β signaling and IL-8 expression and enriched for CSCs, as indicated by mammosphere formation and CSC markers. The TGF-β type I receptor kinase inhibitor LY2157299, a neutralizing TGF-β type II receptor antibody, and SMAD4 siRNA all blocked paclitaxel-induced IL8 transcription and CSC expansion. Moreover, treatment of TNBC xenografts with LY2157299 prevented reestablishment of tumors after paclitaxel treatment. These data suggest that chemotherapy-induced TGF-β signaling enhances tumor recurrence through IL-8–dependent expansion of CSCs and that TGF-β pathway inhibitors prevent the development of drug-resistant CSCs. These findings support testing a combination of TGF-β inhibitors and anticancer chemotherapy in patients with TNBC. PMID:23391723

  8. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Collina, Francesca; Di Bonito, Maurizio; Li Bergolis, Valeria; De Laurentiis, Michelino; Vitagliano, Carlo; Cerrone, Margherita; Nuzzo, Francesco; Cantile, Monica; Botti, Gerardo

    2015-01-01

    Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified.

  9. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Francesca Collina

    2015-01-01

    Full Text Available Triple-negative breast cancer (TNBC has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified.

  10. Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry.

    Science.gov (United States)

    Brewster, Abenaa M; Chavez-MacGregor, Mariana; Brown, Powel

    2014-12-01

    Breast cancer incidence is increasing worldwide, and breast cancer-related mortality is highest in women of African ancestry, who are more likely to have basal-like or triple-negative breast cancer (TNBC) than are women of European ancestry. Identification of cultural, epidemiological, and genetic risk factors that predispose women of African ancestry to TNBC is an active area of research. Despite the aggressive behaviour of TNBC, achievement of a pathological complete response with chemotherapy is associated with good long-term survival outcomes, and sensitivity to chemotherapy does not seem to differ according to ethnic origin. Discovery of the molecular signalling molecules that define TNBC heterogeneity has led to the development of targeted agents such as inhibitors of poly (ADP-ribose) polymerase-1 and mTOR and immunomodulatory drugs that are in the early stages of clinical testing. First, we summarise the existing published work on the differences reported on the epidemiology, biology, and response to systemic treatment of TNBC between women of African ancestry and white women, and identify some gaps in knowledge. Second, we review the opportunities for development of new therapeutic agents in view of the potential high clinical relevance for patients with TNBC irrespective of race or ethnic origin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer.

    Science.gov (United States)

    Ma, Fei; Ding, Xiaoyan; Fan, Ying; Ying, Jianming; Zheng, Shan; Lu, Ning; Xu, Binghe

    2014-01-01

    Triple-negative breast cancer (TNBC) is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs) presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs. The surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed. Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014). The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003). Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS) in both lymph node positive (LN+) and negative (LN-) cases (both Pbreast cancer.

  12. MiR-940 Inhibited Cell Growth and Migration in Triple-Negative Breast Cancer

    Science.gov (United States)

    Hou, Lingmi; Chen, Maoshan; Yang, Hongwei; Xing, Tianyong; Li, Jingdong; Li, Guangwu; Zhang, Lina; Deng, Shishan; Hu, Jiani; Zhao, Xiaobo; Jiang, Jun

    2016-01-01

    Background Breast cancer is the main type of cancer in women, and triple-negative breast cancer (TNBC) is a unique subtype of breast cancer. The expression of miR-940 has been shown to play an important role in various cancers; however, the role of miR-940 in TNBC remains unknown. Material/Methods The expression of miR-940 in TNBC tissues or cells were tested by qRT-PCR; the expression of miR-940 in cells were overexpressed by miR-940 mimics, and suppressed by anti-miR-940. Bioinformatics algorithms from TargetScanHuman were used to predict the target genes of miR-940. The interaction between miR-940 and ZNF24 was confirmed by dual luciferase assays. The protein level was assayed by Western blot. Results TNBC tissues and cells showed lower miR-940 levels. Conclusions MiR-940 inhibited cellular proliferation and migration in TNBC. PMID:27731867

  13. Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system.

    Directory of Open Access Journals (Sweden)

    Nicholas C D'Amato

    Full Text Available Breast cancers with a basal-like gene signature are primarily triple-negative, frequently metastatic, and carry a poor prognosis. Basal-like breast cancers are enriched for markers of breast cancer stem cells as well as markers of epithelial-mesenchymal transition (EMT. While EMT is generally thought to be important in the process of metastasis, in vivo evidence of EMT in human disease remains rare. Here we report a novel model of human triple-negative breast cancer, the DKAT cell line, which was isolated from an aggressive, treatment-resistant triple-negative breast cancer that demonstrated morphological and biochemical evidence suggestive of phenotypic plasticity in the patient. The DKAT cell line displays a basal-like phenotype in vitro when cultured in serum-free media, and undergoes phenotypic changes consistent with EMT/MET in response to serum-containing media, a unique property among the breast cancer cell lines we tested. This EMT is marked by increased expression of the transcription factor Zeb1, and Zeb1 is required for the enhanced migratory ability of DKAT cells in the mesenchymal state. DKAT cells also express progenitor-cell markers, and single DKAT cells are able to generate tumorspheres containing both epithelial and mesenchymal cell types. In vivo, as few as ten DKAT cells are capable of forming xenograft tumors which display a range of epithelial and mesenchymal phenotypes. The DKAT model provides a novel model to study the molecular mechanisms regulating phenotypic plasticity and the aggressive biology of triple-negative breast cancers.

  14. Selective androgen receptor modulators (SARMs negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

    Directory of Open Access Journals (Sweden)

    Ramesh Narayanan

    Full Text Available The androgen receptor (AR is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer.Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC co-culture signaling studies were performed to understand the mechanisms of action.Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures.1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

  15. Telomerase Activity and Genetic Alterations in Primary Breast Carcinomas

    Directory of Open Access Journals (Sweden)

    Anna Papadopoulou

    2003-03-01

    Full Text Available It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that the ectopic expression of telomerase promotes tumorigenesis via a telomere length-independent mechanism. In this study, the relation between telomerase expression and the extent of chromosomal aberrations was investigated in 62 primary breast carcinomas. Telomerase activity was measured using a polymerase chain reaction-based telomeric repeat amplification protocol assay and 92% of the tumors were found to express telomerase with a relative activity ranging from 0 to 3839.6. Genetic alterations were determined by G-banding and comparative genomic hybridization analysis and 97% of the tumors exhibited chromosomal aberrations ranging from 0 to 44 (average: 10.98. In the overall series, the relationship between telomerase activity levels and genetic changes could be best described by a quadratic model, whereas in tumors with below-average genetic alteration numbers, a significant positive association was recorded between the two variables (coefficient=0.374, P= .017. The relationship between telomerase activity levels and the extent of genetic alteration may reflect the complex effect of telomerase activation upon tumor progression in breast carcinomas.

  16. Predicting Triple-Negative Breast Cancer Subtype Using Multiple Single Nucleotide Polymorphisms for Breast Cancer Risk and Several Variable Selection Methods.

    Science.gov (United States)

    Häberle, Lothar; Hein, Alexander; Rübner, Matthias; Schneider, Michael; Ekici, Arif B; Gass, Paul; Hartmann, Arndt; Schulz-Wendtland, Rüdiger; Beckmann, Matthias W; Lo, Wing-Yee; Schroth, Werner; Brauch, Hiltrud; Fasching, Peter A; Wunderle, Marius

    2017-06-01

    Studies of triple-negative breast cancer have recently been extending the inclusion criteria and incorporating additional molecular markers into the selection criteria, opening up scope for targeted therapies. The screening phases required for studies of this type are often prolonged, since the process of determining the molecular subtype and carrying out additional biomarker assessment is time-consuming. Parameters such as germline genotypes capable of predicting the molecular subtype before it becomes available from pathology might be helpful for treatment planning and optimizing the timing and cost of screening phases. This appears to be feasible, as rapid and low-cost genotyping methods are becoming increasingly available. The aim of this study was to identify single nucleotide polymorphisms (SNPs) for breast cancer risk capable of predicting triple negativity, in addition to clinical predictors, in breast cancer patients. This cross-sectional observational study included 1271 women with invasive breast cancer who were treated at a university hospital. A total of 76 validated breast cancer risk SNPs were successfully genotyped. Univariate associations between each SNP and triple negativity were explored using logistic regression analyses. Several variable selection and regression techniques were applied to identify a set of SNPs that together improve the prediction of triple negativity in addition to the clinical predictors of age at diagnosis and body mass index (BMI). The most accurate prediction method was determined by cross-validation. The SNP rs10069690 (TERT, CLPTM1L) was the only significant SNP (corrected p = 0.02) after correction of p values for multiple testing in the univariate analyses. This SNP and three additional SNPs from the genes RAD51B, CCND1, and FGFR2 were selected for prediction of triple negativity. The addition of these SNPs to clinical predictors increased the cross-validated area under the curve (AUC) from 0.618 to 0.625. Age at

  17. A case of Meigs syndrome mimicking metastatic breast carcinoma

    Directory of Open Access Journals (Sweden)

    Al Mufti Ragheed

    2009-01-01

    Full Text Available Abstract Background Adnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing pleural effusions, ascites and adnexal masses, the probability of disseminated disease is high. Nevertheless, benign ovarian masses can mimic this clinical picture when they are associated with Meigs' syndrome making the work-up and management of these patients challenging. To our knowledge, there are no similar reports in the literature and therefore we present this case to highlight this entity. Case presentation A 56-year old woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left ovary, a small amount of ascites and a large right pleural effusion. Serum tumour markers showed a raised CA125 supporting the malignant nature of the ovarian mass. The cytology from the pleural effusion was indeterminate but thoracoscopic biopsy failed to show malignancy. The patient was strongly against mastectomy and she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform breast conserving surgery. After a good response to the hormone manipulation, the patient had breast conserving surgery, axillary sampling and laparoscopic excision of the ovarian mass which was eventually found to be a benign ovarian fibroma. Conclusion Despite the high probability of disseminated malignancy when an ovarian mass associated with ascites if found in a patient with a breast cancer and pleural effusion, clinicians should be aware about rare benign syndromes, like Meigs', which may mimic a similar picture and mislead the diagnosis and management plan.

  18. Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: New discoveries and practical insights for drug development.

    Science.gov (United States)

    Costa, Ricardo; Shah, Ami N; Santa-Maria, Cesar A; Cruz, Marcelo R; Mahalingam, Devalingam; Carneiro, Benedito A; Chae, Young Kwang; Cristofanilli, Massimo; Gradishar, William J; Giles, Francis J

    2017-02-01

    Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor+ and HER2+ breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epidermal Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Relationship between molecular subtype of invasive breast carcinoma and expression of gross cystic disease fluid protein 15 and mammaglobin.

    Science.gov (United States)

    Lewis, Gloria H; Subhawong, Andrea Proctor; Nassar, Hind; Vang, Russell; Illei, Peter B; Park, Ben Ho; Argani, Pedram

    2011-04-01

    We investigated the expression of gross cystic disease fluid protein 15 (GCDFP) and mammaglobin (MGB) by immunohistochemical analysis in 71 invasive breast carcinomas (IBCs) subtyped into luminal (A and B), HER2, basal-like carcinoma (BLC), and unclassified triple-negative carcinoma (UTNC) by established surrogate immunohistochemical profiles. GCDFP and MGB were less likely to be expressed in BLC than in HER2 cancers (P = .000021 and P = .013, respectively) or luminal cancers (P = .00002 and P = .00008, respectively). However, the difference in GCDFP or MGB expression between HER2 and luminal cancers was not significant (P = 1.0 and P = .671, respectively). Our results suggest that luminal cancers demonstrate similar degrees of apocrine differentiation as HER2 cancers. Most BLCs and UTNCs are negative for MGB and GCDFP. Correlation with clinical findings may be needed to exclude the possibility of a metastasis to the breast when BLCs or UTNCs are encountered in a limited sample such as a core biopsy sample.

  20. ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma

    DEFF Research Database (Denmark)

    Porter, Sarah; Span, Paul N; Sweep, Fred C G J

    2006-01-01

    We recently undertook expression profiling of all 19 human ADAMTS metalloproteinases (a disintegrin and metalloproteinase with thrombospondin motifs) in malignant and non-neoplastic breast tissue and showed that 11 of the ADAMTS genes are dysregulated in breast carcinoma. We identified a subgroup...... of ADAMTSs, based on functional and amino acid sequence similarity (ADAMTS1, 4, 5, 8 and 15), to be the focus of further study in breast carcinoma. Further RNA expression analysis by real-time PCR on a different cohort of 229 patients with breast cancer has identified ADAMTS8 as a predictor of poor overall...... breast carcinoma, fitted the expectation that relatively high expression levels of ADAMTS8 together with low expression levels of ADAMTS15 seen in human breast carcinoma are associated with a poor clinical outcome. In summary, ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients...

  1. Effect of radiotherapy after breast-conserving surgery in older patients with early breast cancer and breast ductal carcinoma in situ: a meta-analysis

    OpenAIRE

    Huang, Xuan-zhang; Chen, You; Chen, Wen-Jun; Zhang, Xi; Wu, Cong-cong; Zhang, Chao-ying; Sun, Shuang-shuang; Wu, Jian

    2017-01-01

    Background There are no consistent agreements on whether radiotherapy after breast-conserving surgery (BCS) could provide local control and survival benefit for older patients with early breast cancer or breast ductal carcinoma in situ (DCIS). The present study aimed to evaluate the efficacy of radiotherapy after BCS in older patients with early breast cancer or DCIS. Results Radiotherapy could reduce the risk of local relapse in older patients with early breast cancer. The 5-year AR of local...

  2. Prognostic, quantitative histopathologic variables in lobular carcinoma of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    BACKGROUND: A retrospective investigation of 53 consecutively treated patients with operable lobular carcinoma of the breast, with a median follow-up of 6.6 years, was performed to examine the prognostic value of quantitative histopathologic parameters.METHODS: The measurements were performed...... of disease, vv(nuc), MI, and NI were of significant independent, prognostic value. On the basis of the multivariate analyses, a prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed.CONCLUSION: Quantitative histopathologic variables are of value...... for objective grading of malignancy in lobular carcinomas. The new parameter--estimates of the mean nuclear volume--is highly reproducible and suitable for routine use. However, larger and prospective studies are needed to establish the true value of the quantitative histopathologic variables in the clinical...

  3. Breast carcinoma with osteoclast-like giant cells

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Lauridsen, M C; Sørensen, Flemming Brandt

    2001-01-01

    Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the female breast. The clinical course, histological, immunohistochemical and ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast-like multinucleated giant cells (OMGCs) are reviewed and a new ...... case is presented. The median patient age of all patients included in the review was 42 years, the tumour was located in the upper outer quadrant and the mammographic and gross findings were of a well-defined tumour of dark-brown colour, resembling a metastatic melanoma. Follow-up data...... stroma. Immunohistochemical and ultrastructural studies have claimed a benign histiocytic nature of the OMGCs; they may represent a special type of polykaryon, distinct from both osteoclasts and inflammatory giant cells....

  4. Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

    Science.gov (United States)

    Su, Yu-Cheng; Burnouf, Pierre-Alain; Chuang, Kuo-Hsiang; Chen, Bing-Mae; Cheng, Tian-Lu; Roffler, Steve R.

    2017-06-01

    Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

  5. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Elena V Rosca

    Full Text Available We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  6. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Science.gov (United States)

    Rosca, Elena V; Penet, Marie-France; Mori, Noriko; Koskimaki, Jacob E; Lee, Esak; Pandey, Niranjan B; Bhujwalla, Zaver M; Popel, Aleksander S

    2014-01-01

    We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  7. Elucidation of altered pathways in tumor-initiating cells of triple-negative breast cancer

    DEFF Research Database (Denmark)

    Christensen, Anne G; Ehmsen, Sidse; Terp, Mikkel G

    2017-01-01

    A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow...... reduction was also observed using patient-derived primary cancer cells. Further, blocking NF-κB signaling in mice transplanted with tumor-initiating cells significantly reduced tumor outgrowth. Our study demonstrates that suppressed apoptosis, activation of pathways associated with cell viability and CSCs...... their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics. Within these pairs, one, but not the other, resulted...

  8. The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.; Anderson, Redmond-Craig; Zeng, Chenbo; Xu, Kuiying; Hou, Catherine; McDonald, Elizabeth S.; Pryma, Daniel A.; Mach, Robert H., E-mail: rmach@mail.med.upenn.edu

    2015-11-27

    Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with

  9. Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin

    Directory of Open Access Journals (Sweden)

    Danica L. Rowe

    2009-09-01

    Full Text Available In the current study, we sought to examine the effects of curcumin in a specific type of breast cancer called triple negative breast cancer. These cancers lack expression of the estrogen and progesterone receptors and do not over-express HER2. Current treatment for triple negative breast cancers is limited to cytotoxic chemotherapy, and upon relapse, there are not any therapies currently available. We demonstrate here that the bioactive food compound curcumin induces DNA damage in triple negative breast cancer cells in association with phosphorylation, increased expression, and cytoplasmic retention of the BRCA1 protein. In addition, curcumin promotes apoptosis and prevents anchorage-independent growth and migration of triple negative breast cancer cells. Apoptosis and BRCA1 modulation were not observed in non-transformed mammary epithelial cells, suggesting curcumin may have limited non-specific toxicity. This study suggests that curcumin and potentially curcumin analogues should be tested further in the context of triple negative breast cancer. These results are novel, having never been previously reported, and suggest that curcumin could provide a novel, non-toxic therapy, which could lead to improved survival for patients with triple negative breast cancer. Curcumin should be studied further in this subset of breast cancer patients, for whom treatment options are severely limited.

  10. Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

    Directory of Open Access Journals (Sweden)

    Giannos A

    2015-07-01

    Full Text Available Aris Giannos,1 Martin Filipits,2 Flora Zagouri,2,3 Anita Brandstetter,2 Alexandra Tsigginou,1 Maria Sotiropoulou,4 Irene Papaspyrou,4 Theodoros N Sergentanis,5 Theodora Psaltopoulou,5 Alexandros Rodolakis,1 Aris Antsaklis,1 Meletios-Athanasios Dimopoulos,2 Constantine Dimitrakakis1 1Department of Obstetrics and Gynaecology, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 2Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; 3Department of Clinical Therapeutics, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 4Department of Pathology, Alexandra General Hospital, Athens, Greece; 5Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC.Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score, clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression, and overall survival were evaluated.Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26–1.70, P=0.393.Conclusion: AR expression does not seem to play a prognostic role in TNBC. Keywords: biomarkers, prognosis, AR, triple negative breast cancer

  11. Prevalence of papillomaviruses, polyomaviruses, and herpesviruses in triple-negative and inflammatory breast tumors from algeria compared with other types of breast cancer tumors.

    Science.gov (United States)

    Corbex, Marilys; Bouzbid, Sabiha; Traverse-Glehen, Alexandra; Aouras, Hayette; McKay-Chopin, Sandrine; Carreira, Christine; Lankar, Abdelaziz; Tommasino, Massimo; Gheit, Tarik

    2014-01-01

    The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC) and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups. One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria) to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses) using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology. Viral DNA was found in 22 (17.9%) of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type) than non-IBC tumors (30% vs. 13%, pbreast cancer phenotypes (IBC, triple-negative). While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings.

  12. The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential

    Directory of Open Access Journals (Sweden)

    Kun-Chun Chiang

    2016-04-01

    Full Text Available Regarding breast cancer treatment, triple negative breast cancer (TNBC is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl-1α,25(OH2D3, the newly-synthesized 1α,25(OH2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9 activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.

  13. Overweight as a Prognostic Factor for Triple-Negative Breast Cancers in Chinese Women.

    Directory of Open Access Journals (Sweden)

    Shuang Hao

    Full Text Available Obesity is associated with poorer outcomes in patients with hormone receptor-positive breast cancers, but this association is not well established for women with triple-negative breast cancers (TNBC. Here, we investigated the prognostic effects of body mass index (BMI on clinical outcomes in patients with TNBC.We identified 1106 patients with TNBC who met the inclusion criteria and were treated between January 2002 and June 2012. Clinical and biological features were collected to evaluate the relation between BMI and breast cancer-specific survival (BCSS and overall survival (OS after controlling for other clinically significant variables.Of 1106 patients, 656 (59.3% were normal weight (BMI ≤24 and 450 patients (40.7% were overweight(BMI>24. Median follow-up time was 44.8 months. Breast cancer specific death was observed in 140 patients. After adjusting for clinicopathologic risk factors, overweight was associated with OS (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.04-2.06, P =0.028 but not BCSS (HR: 1.34, 95% CI: 0.90-2.01, P =0.15in all the patients with TNBC. When stratified with menopausal status, overweight was associated with BCSS and OS (HR: 2.27, 95% CI: 1.11-4.63, P = 0.024 and HR: 2.16, 95% CI: 1.21-3.87, P = 0.010, respectively in premenopausal women. BMI was not associated with BCSS or OS in postmenopausal women.Overweight is an independent prognostic factor of OS in all women with TNBC, and menopause status may be a mitigating factor. Among premenopausal women, overweight women are at a greater risk of poor prognosis than normal weight women. If validated, these findings should be considered in developing preventive programs.

  14. Trends of triple negative breast cancer research (2007-2015): A bibliometric study.

    Science.gov (United States)

    Wang, Yiran; Zhai, Xiao; Liu, Chuan; Wang, Ning; Wang, Yajie

    2016-11-01

    Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. However, there have been limited data to evaluate the trend of TNBC research. This study aims to investigate the trend of TNBC research and compare the contribution of research from different regions, organizations, and authors. TNBC-related publications from 2007 to 2015 were retrieved from the Web of Science database. Excel 2013 (Redmond, Washington, USA), GraphPad Prism 5 (GraphPad Prism Software Inc., San Diego, CA), and VOSviewer (Leiden University, Leiden, Netherlands) software were used to analyze the trend of TNBC research. This article does not contain any studies with human participants or animals performed by any of the authors. A total of 1695 papers were identified and were cited 34,078 times with a time limit of May 27, 2016. The United States accounted for 43.10% of the articles, 57.59% of the citations, and the highest H-index (64). China ranked second in total number of articles, but seventh in citation frequency (1998) and ninth in H-index (21). The journal Breast Cancer Research and Treatment had the highest number of publications. The author, Narod SA, has published the most papers in this field (30). The keyword "receptor" was mentioned the most, 1489 times, and the word "myeloid cell leukemia-1 (MCL-1)" was the latest hot spot by 2015. Literature growth related to TNBC is expanding rapidly in recent years. The quality of the articles from China still requires improvement. Newest progress of the TNBC research may be released by the journal Breast Cancer Research and Treatment first. Narod SA, Gonzalez-Angulo AM, and Hortobagyi GN may be good candidates for collaborative research in this field. MCL-1 is an emerging topic that should be closely observed.

  15. Opportunities for improving triple-negative breast cancer outcomes: results of a population-based study.

    Science.gov (United States)

    Rapiti, Elisabetta; Pinaud, Kim; Chappuis, Pierre O; Viassolo, Valeria; Ayme, Aurélie; Neyroud-Caspar, Isabelle; Usel, Massimo; Bouchardy, Christine

    2017-03-01

    Triple-negative breast cancer (TNBC) is associated with a poor prognosis. Surgery, radiotherapy, chemotherapy, and referral for genetic counseling are the standard of care. We assessed TNBC prevalence, management, and outcome using data from the population-based Geneva cancer registry. 2591 women had a first invasive stage I-III breast cancer diagnosed between 2003 and 2011. We compared TNBC to other breast cancers (OBC) by χ(2) -test and logistic regression. Kaplan-Meier survival curves, up to 31-12-2014, were compared using log-rank test. TNBC risk of mortality overall (OS) and for breast cancer (BCSS) was evaluated through Cox models. Linkage with the Oncogenetics and Cancer Prevention Unit (OCPU) database of the Geneva University Hospitals provided genetic counseling information. TNBC patients (n = 192, 7.4%) were younger, more often born in Africa or Central-South America than OBC, had larger and more advanced tumors. 18% of TNBC patients did not receive chemotherapy. Thirty-one (17%) TNBC women consulted the OCPU, 39% among those aged P P < 0.001). The mortality risks remained significant after adjustment for other prognostic variables. The strongest determinants of mortality were age, place of birth, and lymph node status. A substantial proportion of TNBC patients in Geneva did not receive optimal care. Over 60% of eligible women did not receive genetic counseling and 18% did not receive chemotherapy. To improve TNBC prognosis, comprehensive care as recommended by standard guidelines should be offered to all patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  16. KIF14 Promotes AKT Phosphorylation and Contributes to Chemoresistance in Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stina M. Singel

    2014-03-01

    Full Text Available Despite evidence that kinesin family member 14 (KIF14 can serve as a prognostic biomarker in various solid tumors, how it contributes to tumorigenesis remains unclear. We observed that experimental decrease in KIF14 expression increases docetaxel chemosensitivity in estrogen receptor–negative/progesterone receptor–negative/human epidermal growth factor receptor 2-negative, “triple-negative” breast cancers (TNBC. To investigate the oncogenic role of KIF14, we used noncancerous human mammary epithelial cells and ectopically expressed KIF14 and found increased proliferative capacity, increased anchorage-independent grown in vitro, and increased resistance to docetaxel but not to doxorubicin, carboplatin, or gemcitabine. Seventeen benign breast biopsies of BRCA1 or BRCA2 mutation carriers showed increased KIF14 mRNA expression by fluorescence in situ hybridization compared to controls with no known mutations in BRCA1 or BRCA2, suggesting increased KIF14 expression as a biomarker of high-risk breast tissue. Evaluation of 34 cases of locally advanced TNBC showed that KIF14 expression significantly correlates with chemotherapy-resistant breast cancer. KIF14 knockdown also correlates with decreased AKT phosphorylation and activity. Live-cell imaging confirmed an insulin-induced temporal colocalization of KIF14 and AKT at the plasma membrane, suggesting a potential role of KIF14 in promoting activation of AKT. An experimental small-molecule inhibitor of KIF14 was then used to evaluate the potential anticancer benefits of downregulating KIF14 activity. Inhibition of KIF14 shows a chemosensitizing effect and correlates with decreasing activation of AKT. Together, these findings show an early and critical role for KIF14 in the tumorigenic potential of TNBC, and therapeutic targeting of KIF14 is feasible and effective for TNBC.

  17. Lactoferrin- Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple Negative Breast Cancer Phenotypes

    Science.gov (United States)

    Ha, Ngoc-Han; Nair, Vasudha; Reddy, Divijendra Natha Sirigiri; Mudvari, Prakriti; Ohshiro, Kazufumi; Ghanta, Krishna Sumanth; Pakala, Suresh B.; Li, Da-Qiang; Costa, Luis; Lipton, Allan; Badwe, Rajendra A.; Fuqua, Suzanne; Wallon, Margaretha; Prendergast, George C.; Kumar, Rakesh

    2013-01-01

    Triple-negative breast cancer (TNBC) is characterized by the lack of expression of ERα, PR and HER-2 receptors and the pathway(s) responsible for this downregulation and thus aggressiveness, remains unknown. Here we discovered that lactoferrin (Lf) efficiently downregulates the levels of ERα, PR and HER-2 receptors in a proteasome-dependent manner in breast cancer cells, and accounts for the loss of responsiveness to ER- or HER-2- targeted therapies. Further we found that Lf increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that Lf directly stimulates the transcription of endothelin-1 (ET-1), a secreted pro-invasive polypeptide that acts through a specific receptor ET(A)R, leading to secretion of bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor antagonist drug completely blocked Lf-dependent motility and invasiveness of breast cancer cells. Physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue Lf and ET-1 levels in TNBC patients as compared to those in ER+ cases. These findings describe the first physiologically relevant polypeptide as a functional determinant of downregulating all three therapeutic receptors in breast cancer which utilizes another secreted ET-1 system to confer invasiveness. Results presented here provide proof-of-principle evidence in support of therapeutic effectiveness of ET-1 receptor antagonist to completely block the Lf-induced motility and invasiveness of the TNBC as well as non-TBNC cells, and thus, opening a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug. PMID:22006997

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xuelu Li

    2017-09-01

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

  20. [Metastatic cervical fasciitis revealing invasive lobular breast carcinoma].

    Science.gov (United States)

    Munoz, J; Garcia, C; Joujoux, J-M; Dandurand, M; Meunier, L; Stoebner, P-E

    2015-02-01

    We describe the case of a 71-year-old woman presenting cervical metastatic fasciitis with invasive lobular carcinoma (ILC) of the breast. The patient consulted for a deep and painless skin infiltration of the neck associated with dysphagia and restricted cervical mobility. Skin and muscle biopsies were normal. Muscle fascia biopsy showed a linear infiltration of metastatic cells in "single file", revealing ILC of the right breast. ILCs have a particular metastatic pattern. They can permeate through tissue planes, infiltrate solid organs and spread on serous membranes in an insidious fashion. Our case shows that ILC can metastasise into muscular fascia, causing "fasciitis-like" symptoms. Dermatologists should be aware of this particular pattern of dissemination. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Invasive ductal carcinoma of the breast with large central acellular zones (ring carcinoma): imaging and clinical findings in eight cases.

    Science.gov (United States)

    Connors, Alissa M; Svensson, William E; Sinnett, H Dudley; Shousha, Sami

    2005-10-01

    To review the mammographic and ultrasound appearances in patients who have invasive ductal carcinoma with a central acellular zone (ring carcinoma), as this feature has been reported to be associated with a poorer outcome. Eight patients were identified with ring carcinomas. Two breast radiologists reviewed their mammograms and ultrasound images. Patient records were reviewed to assess outcome. All patients had lesions deep within the breast, adjacent to the chest wall, five lesions were incompletely visualised on mammography. The appearance was of a circumscribed or obscured mass, without microcalcification. Five patients had ultrasound demonstrating a solid well-circumscribed hypoechoic microlobulated lesion. In our series of patients who have a ring carcinoma of the breast, mammographic and ultrasound appearances were similar in all cases and lacked the typical features of malignancy.

  2. Current Status of Poly(ADP-ribose Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    David J. Hiller

    2012-01-01

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive type of breast cancer that is clinically defined as lacking estrogen and progesterone receptors, as well as being ERBB2 (HER-2 negative. Without specific therapeutic targets, TNBC carries a worse prognosis than other types of breast cancer in the absence of therapy. Research has now further differentiated breast cancer into subtypes based on genetic expression patterns. One of these subtypes, basal-like, frequently overlaps with the clinical picture of TNBC. Additionally, both TNBC and basal-like breast cancer link to BRCA mutations. Recent pharmaceutical advances have created a class of drugs, poly(ADP-ribose polymerase (PARP inhibitors, which are showing potential to effectively treat these patients. The aim of this paper is to summarize the basis behind PARP inhibitors and update the current status of their development in clinical trials for the treatment of TNBC.

  3. Prediction of breast cancer recurrence using lymph node metabolic and volumetric parameters from {sup 18}F-FDG PET/CT in operable triple-negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong-il [CHA University, Department of Nuclear Medicine, CHA Bundang Medical Center, Seongnam (Korea, Republic of); Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Yong Joong [Veterans Health Service Medical Center, Seoul (Korea, Republic of); Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Chung, June-Key [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Kang, Keon Wook [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of)

    2017-10-15

    Triple-negative breast cancer has a poor prognosis. We evaluated several metabolic and volumetric parameters from preoperative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the prognosis of triple-negative breast cancer and compared them with current clinicopathologic parameters. A total of 228 patients with triple-negative breast cancer (mean age 47.0 ± 10.8 years, all women) who had undergone preoperative PET/CT were included. The PET/CT metabolic parameters evaluated included maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean, respectively). The volumetric parameters evaluated included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Metabolic and volumetric parameters were evaluated separately for tumor (T) and lymph nodes (N). The prognostic value of these parameters was compared with that of clinicopathologic parameters. All lymph node metabolic and volumetric parameters showed significant differences between patients with and without recurrence. However, tumor metabolic and volumetric parameters showed no significant differences. In a univariate survival analysis, all lymph node metabolic and volumetric parameters (SUVmax-N, SUVpeak-N, SUVmean-N, MTV-N, and TLG-N; all P < 0.001), T stage (P = 0.010), N stage (P < 0.001), and TNM stage (P < 0.001) were significant parameters. In a multivariate survival analysis, SUVmax-N (P = 0.005), MTV (P = 0.008), and TLG (P = 0.006) with TNM stage (all P < 0.001) were significant parameters. Lymph node metabolic and volumetric parameters were significant predictors of recurrence in patients with triple-negative breast cancer after surgery. Lymph node metabolic and volumetric parameters were useful parameters for evaluating prognosis in patients with triple-negative breast cancer by {sup 18}F-FDG PET/CT, rather than tumor parameters. (orig.)

  4. Prediction of breast cancer recurrence using lymph node metabolic and volumetric parameters from (18)F-FDG PET/CT in operable triple-negative breast cancer.

    Science.gov (United States)

    Kim, Yong-Il; Kim, Yong Joong; Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo; Chung, June-Key; Kang, Keon Wook

    2017-06-14

    Triple-negative breast cancer has a poor prognosis. We evaluated several metabolic and volumetric parameters from preoperative (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the prognosis of triple-negative breast cancer and compared them with current clinicopathologic parameters. A total of 228 patients with triple-negative breast cancer (mean age 47.0 ± 10.8 years, all women) who had undergone preoperative PET/CT were included. The PET/CT metabolic parameters evaluated included maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean, respectively). The volumetric parameters evaluated included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Metabolic and volumetric parameters were evaluated separately for tumor (T) and lymph nodes (N). The prognostic value of these parameters was compared with that of clinicopathologic parameters. All lymph node metabolic and volumetric parameters showed significant differences between patients with and without recurrence. However, tumor metabolic and volumetric parameters showed no significant differences. In a univariate survival analysis, all lymph node metabolic and volumetric parameters (SUVmax-N, SUVpeak-N, SUVmean-N, MTV-N, and TLG-N; all P P = 0.010), N stage (P P P = 0.005), MTV (P = 0.008), and TLG (P = 0.006) with TNM stage (all P triple-negative breast cancer after surgery. Lymph node metabolic and volumetric parameters were useful parameters for evaluating prognosis in patients with triple-negative breast cancer by (18)F-FDG PET/CT, rather than tumor parameters.

  5. Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Kim

    2017-07-01

    Full Text Available Background Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. Methods A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2% had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC, and 19 (52.8% had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC and 13 invasive ductal and micropapillary carcinomas (IDMPC. Results The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2 status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05. According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05. Conclusions In contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.

  6. Carcinoma espinocelular da mama: relato de um caso Squamous cell carcinoma of the breast tissue: a case report

    Directory of Open Access Journals (Sweden)

    Rubens José Pereira

    1999-08-01

    Full Text Available O carcinoma espinocelular do parênquima mamário é um tipo raro de neoplasia, representando menos de 1% de todos os carcinomas mamários. Esse trabalho relata a condução de um caso diagnosticado e tratado no Serviço de Ginecologia e Mama do Hospital Araújo Jorge/ACCG. São discutidos a apresentação clínica, o diagnóstico e o prognóstico destes tumores.Squamous cell carcinoma of the mammary tissue is a very rare neoplasm, representing less than 1% of all breast carcinomas. The present study reports a case of squamous cell carcinoma of the breast, treated at the Hospital Araújo Jorge/ACCG. The tumor diagnosis, treatment and prognosis are also discussed.

  7. Uroplakin II Expression in Breast Carcinomas Showing Apocrine Differentiation: Putting Some Emphasis on Invasive Pleomorphic Lobular Carcinoma as a Potential Mimic of Urothelial Carcinoma at Metastatic Sites.

    Science.gov (United States)

    Tajima, Shogo; Koda, Kenji

    2016-01-01

    Uroplakin II antibody is exclusively specific for urothelial carcinoma. Nonurothelial carcinoma has not been reported to be immunoreactive for uroplakin II. In the present study, we hypothesized that breast carcinoma showing apocrine differentiation, such as invasive pleomorphic lobular carcinoma (IPLC) and apocrine carcinoma (AC), stains positive for uroplakin II. We identified 6 cases of IPLC between 2000 and 2014 by searching a computerized pathological database. We randomly selected 10 cases of each classic invasive lobular carcinoma (cILC) and AC and five cases of apocrine metaplasia (AM) that coexisted in a surgically resected breast carcinoma specimen. Immunohistochemistry was performed for uroplakin II, GATA3, CK7, CK20, and other representative markers positive for urothelial carcinoma. All cases of IPLC, AC, and AM, except those of cILC, showed immunoreactivity for uroplakin II. Poorly differentiated urothelial carcinoma sometimes shows similar morphology to IPLC with the following immunophenotype: CK7+, CK20-, GATA3+, and uroplakin II+. In the present study, this immunophenotype was observed in all the cases of IPLC and AC. Therefore, when studying metastatic, poorly differentiated carcinoma showing the aforementioned immunophenotype, we should consider the possibility of it being IPLC in addition to metastatic urothelial carcinoma.

  8. Novel therapeutic strategies for patients with triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Zhang J

    2016-10-01

    Full Text Available Jun-Fei Zhang,1 Jia Liu,1,2 Yu Wang,1,2 Bin Zhang1,2 1Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, People’s Republic of China; 2Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, People’s Republic of China Abstract: Triple-negative breast cancer (TNBC represents a very heterogeneous group of breast diseases. Currently, the backbone of therapy for TNBC is mainly chemotherapy as there are no effective specific targeted agents approved to treat TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. Therefore, new targeted strategies are, accordingly, urgently needed. This article discusses the recent developments in targeted agents explored for TNBC, aiming to offer novel therapeutic strategies that can potentially assist in designing personalized therapeutics in the future as well as provide the basis for further research in an attempt to target TNBC. Keywords: therapeutic strategies, TNBC, targeted agents

  9. KEY PLAYERS IN CHOLINE METABOLIC REPROGRAMMING IN TRIPLE NEGATIVE BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Egidio Iorio

    2016-09-01

    Full Text Available Triple negative breast cancer (TNBC, defined by lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2 (HER2, is still a clinical challenge despite progress in breast cancer (BC care. 1H magnetic resonance spectroscopy (MRS allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up, and identify new targets for treatment. Several studies have shown an altered phosphatidylcholine (PtdCho metabolism in TNBCs, both in patients and in experimental models. Up-regulation of choline kinase-alpha, an enzyme of the Kennedy pathway that phosphorylates free choline (Cho to phosphocholine (PCho, is a major contributor to the increased PCho content detected in TNBCs. Phospholipase-mediated PtdCho headgroup hydrolysis also contributes to the build-up of a PCho pool in TNBC cells. The oncogene-driven PtdCho cycle appears to be fine tuned in TNBC cells in at least three ways: by modulating the choline import, by regulating the activity or expression of specific metabolic enzymes, and by contributing to the rewiring of the entire metabolic network. Thus, only by thoroughly dissecting these mechanisms, it will be possible to effectively translate this basic knowledge into further development and implementation of Cho-based imaging techniques and novel classes of therapeutics.

  10. Curcumin-derivative nanomicelles for the treatment of triple negative breast cancer.

    Science.gov (United States)

    Taurin, Sebastien; Nehoff, Hayley; Diong, Jasper; Larsen, Lesley; Rosengren, Rhonda J; Greish, Khaled

    2013-08-01

    Triple negative breast cancer (TNBC) is a subtype of breast cancer characterized by its poor outcome and a lack of targeted therapies. Recently, our laboratory has developed a second generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71) that shows potent in vitro cytotoxicity. RL71 is hydrophobic with poor bioavailability which limits its clinical development. We have designed styrene-co-maleic acid (SMA) micelles encapsulating 5, 10 or 15% RL71 by weight/weight ratio to improve its solubility and pharmacokinetic profile. The micelles charge, size and release rate were characterized. We evaluated their cytotoxicity against TNBC cell lines. The internalization of the drug inside the cells was measured by HPLC and the efficiency of the micelles was tested using a tumor spheroid model. The micelles exhibited mean diameters of 125-185 nm and had a neutral charge. SMA-RL71 micelles have a cytotoxicity profile comparable to the free drug against several TNBC cell lines. Moreover, the 15% loaded micelles increased the stability of RL71 and demonstrated higher activity in a tumor spheroid model. The current study demonstrates the efficiency of SMA for drug delivery, the influence of physicochemical characteristics on cytotoxicity, and provides the basis for preclinical testing in vivo.

  11. Quercetin regulates β-catenin signaling and reduces the migration of triple negative breast cancer.

    Science.gov (United States)

    Srinivasan, Asha; Thangavel, Chellappagounder; Liu, Yi; Shoyele, Sunday; Den, Robert B; Selvakumar, Ponniah; Lakshmikuttyamma, Ashakumary

    2016-05-01

    Triple negative breast cancer (TNBC) is characterized by a lack in estrogen, progesterone, and epidermal growth factor 2 receptors. TNBC exhibits most of the characteristics of basal-like and claudin-low breast cancer subtypes. The main contributor in the mortality of TNBC is due to the higher invasive and migratory ability of these tumor cells. Some plant flavonoids inhibit the epithelial mesenchymal transition (EMT) of tumor cells and suppress cancer metastasis. In this study, we aimed to determine whether the flavonoid quercetin is effective in modulating the molecular signaling associated with EMT in TNBC. Our data indicated that quercetin can induce the expression of E-cadherin and also downregulate vimentin levels in TNBC. The ability of quercetin to modulate these EMT markers resulted in a mesenchymal-to-epithelial transition (MET). Quercetin-induced MET was linked with the alteration of nuclear localization of β-catenin and modulation of β-catenin target genes such as cyclin D1 and c-Myc. Furthermore, we observed that quercetin induced the anti-tumor activity of doxorubicin by inhibiting the migratory ability of TNBC cells. These results suggested that quercetin may inhibit TNBC metastasis and also improve the therapeutic efficacy of existing chemotherapeutic drugs. © 2015 Wiley Periodicals, Inc.

  12. Mechanisms of resistance of chemotherapy in early-stage triple negative breast cancer (TNBC).

    Science.gov (United States)

    Wein, Lironne; Loi, Sherene

    2017-08-01

    Triple negative breast cancer (TNBC) a clinically aggressive subtype of breast cancer with poor outcomes. Chromosomal instability is a hallmark of many TNBCs, and likely underlies its ability to adapt and rapidly become resistant to chemotherapy. A study of residual disease after neoadjuvant chemotherapy have identified biological mechanisms driving this resistance to chemotherapy. Copy number amplifications such as MCL1, MYC and JAK2, as well as PTEN deletions or mutations have all been identified at a higher frequency in residual disease, suggesting they may play a role in de novo or acquired chemotherapy resistance. Increased copy number and expression of the PIM1 proto-oncogene in TNBC has also been identified as a new target of chemotherapy resistance. However, given the genomic instability and subclonal nature of driver mutations in TNBC, single agent targeted therapy is unlikely to be effective. Lately immune evasion has also been identified as another key characteristic of poor prognostic and chemo-resistant primary TNBCs. Combinations of checkpoint inhibition with targeted therapy and/or chemotherapy are currently being investigated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

    Science.gov (United States)

    Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-i; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2017-01-01

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors. PMID:27861147

  14. CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer.

    Science.gov (United States)

    Paret, Claudia; Simon, Petra; Vormbrock, Kirsten; Bender, Christian; Kölsch, Anne; Breitkreuz, Andrea; Yildiz, Özlem; Omokoko, Tana; Hubich-Rau, Stefanie; Hartmann, Christoph; Häcker, Sabine; Wagner, Meike; Roldan, Diana Barea; Selmi, Abderaouf; Türeci, Özlem; Sahin, Ugur

    2015-09-22

    Triple-negative breast cancer (TNBC) is a high medical need disease with limited treatment options. CD8+ T cell-mediated immunotherapy may represent an attractive approach to address TNBC. The objectives of this study were to assess the expression of CXorf61 in TNBCs and healthy tissues and to evaluate its capability to induce T cell responses. We show by transcriptional profiling of a broad comprehensive set of normal human tissue that CXorf61 expression is strictly restricted to testis. 53% of TNBC patients express this antigen in at least 30% of their tumor cells. In CXorf61-negative breast cancer cell lines CXorf61 expression is activated by treatment with the hypomethylating agent 5-aza-2'-deoxycytidine. By vaccination of HLA-A*02-transgenic mice with CXorf61 encoding RNA we obtained high frequencies of CXorf61-specific T cells. Cloning and characterization of T cell receptors (TCRs) from responding T cells resulted in the identification of the two HLA-A*0201-restricted T cell epitopes CXorf6166-74 and CXorf6179-87. Furthermore, by in vitro priming of human CD8+ T cells derived from a healthy donor recognizing CXorf6166-74 we were able to induce a strong antigen-specific immune response and clone a human TCR recognizing this epitope. In summary, our data confirms this antigen as promising target for T cell based therapies.

  15. Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value.

    Science.gov (United States)

    Stirzaker, Clare; Zotenko, Elena; Song, Jenny Z; Qu, Wenjia; Nair, Shalima S; Locke, Warwick J; Stone, Andrew; Armstong, Nicola J; Robinson, Mark D; Dobrovic, Alexander; Avery-Kiejda, Kelly A; Peters, Kate M; French, Juliet D; Stein, Sandra; Korbie, Darren J; Trau, Matt; Forbes, John F; Scott, Rodney J; Brown, Melissa A; Francis, Glenn D; Clark, Susan J

    2015-02-02

    Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple-negative breast cancer (TNBC) and matched normal samples. We identify differentially methylated regions (DMRs) enriched with promoters associated with transcription factor binding sites and DNA hypersensitive sites. Importantly, we stratify TNBCs into three distinct methylation clusters associated with better or worse prognosis and identify 17 DMRs that show a strong association with overall survival, including DMRs located in the Wilms tumour 1 (WT1) gene, bi-directional-promoter and antisense WT1-AS. Our data reveal that coordinated hypermethylation can occur in oestrogen receptor-negative disease, and that characterizing the epigenetic framework provides a potential signature to stratify TNBCs. Together, our findings demonstrate the feasibility of profiling the cancer methylome with limited archival tissue to identify regulatory regions associated with cancer.

  16. Combined Phosphoproteomics and Bioinformatics Strategy in Deciphering Drug Resistant Related Pathways in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Xinyu Deng

    2014-01-01

    Full Text Available Because of the absence of a clear therapeutic target for triple negative breast cancer (TNBC, conventional chemotherapy is the only available systemic treatment option for these patients. Despite chemotherapy treatment, TNBC patients still have worse prognosis when compared with other breast cancer patients. The study is to investigate unique phosphorylated proteins expressed in chemoresistant TNBC cell lines. In the current study, twelve TNBC cell lines were subjected to drug sensitivity assays against chemotherapy drugs docetaxel, doxorubicin, gemcitabine, and cisplatin. Based on their half maximal inhibitory concentrations, four resistant and two sensitive cell lines were selected for further analysis. The phosphopeptides from these cells were enriched with TiO2 beads and fractionated using strong cation exchange. 1,645 phosphoprotein groups and 9,585 unique phosphopeptides were identified by a high throughput LC-MS/MS system LTQ-Orbitrap. The phosphopeptides were further filtered with Ascore system and 1,340 phosphoprotein groups, 2,760 unique phosphopeptides, and 4,549 unique phosphosites were identified. Our study suggested that differentially phosphorylated Cdk5, PML, AP-1, and HSF-1 might work together to promote vimentin induced epithelial to mesenchymal transition (EMT in the drug resistant cells. EGFR and HGF were also shown to be involved in this process.

  17. Piperine inhibits the growth and motility of triple-negative breast cancer cells.

    Science.gov (United States)

    Greenshields, Anna L; Doucette, Carolyn D; Sutton, Kimberly M; Madera, Laurence; Annan, Henry; Yaffe, Paul B; Knickle, Allison F; Dong, Zhongmin; Hoskin, David W

    2015-02-01

    Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated the effect of piperine on the growth and motility of triple-negative breast cancer (TNBC) cells. Piperine inhibited the in vitro growth of TNBC cells, as well as hormone-dependent breast cancer cells, without affecting normal mammary epithelial cell growth. Exposure to piperine decreased the percentage of TNBC cells in the G2 phase of the cell cycle. In addition, G1- and G2-associated protein expression was decreased and p21(Waf1/Cip1) expression was increased in piperine-treated TNBC cells. Piperine also inhibited survival-promoting Akt activation in TNBC cells and caused caspase-dependent apoptosis via the mitochondrial pathway. Interestingly, combined treatment with piperine and γ radiation was more cytotoxic for TNBC cells than γ radiation alone. The in vitro migration of piperine-treated TNBC cells was impaired and expression of matrix metalloproteinase-2 and -9 mRNA was decreased, suggesting an antimetastatic effect by piperine. Finally, intratumoral administration of piperine inhibited the growth of TNBC xenografts in immune-deficient mice. Taken together, these findings suggest that piperine may be useful in the treatment of TNBC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Therapeutic Advances and New Directions for Triple-Negative Breast Cancer.

    Science.gov (United States)

    Andreopoulou, Eleni; Kelly, Catherine M; McDaid, Hayley M

    2017-03-01

    Triple-negative breast cancer (TNBC) is a molecularly diverse grouping with poor prognosis for which chemotherapy remains the foundation of treatment. The molecular heterogeneity of the disease rationalizes its diverse biological behavior and differential response to treatment. Estimates of up to 20% of patients diagnosed have germline mutations in DNA-damage repair-pathway genes, namely BRCA1 and 2, and this can be used to select patients likely to respond to platinums and/or inhibitors of poly(ADP-ribose) polymerase (PARP). Similar strategies can be utilized in other subtypes of TNBC that have 'BRCA-like' tumor biology due to the presence of mutations in alternate DNA-damage repair genes. The diverse biological behavior of TNBC and its variable response to chemotherapy were largely decoded following genotyping studies that enabled the identification of distinct molecular subtypes, such that the biological and genetic heterogeneity of the disease could be understood. This subsequently enabled the identification of therapeutic 'vulnerabilities' for each subtype that encompass biological processes including proliferation, DNA repair, apoptosis, angiogenesis, immune modulation, and invasion and metastasis. To expedite the development of therapies for high-risk, early-stage breast cancer, we have adopted novel trial designs and re-defined endpoints as surrogates of clinical outcomes. The purpose of this review is to highlight the current standard and experimental treatment options for TNBC.

  19. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Cheang Maggie CU

    2007-07-01

    Full Text Available Abstract Background Basal-like breast cancer has been extensively characterized on the basis of gene expression profiles, but it is becoming increasingly common for these tumors to be defined on the basis of immunohistochemical (IHC staining patterns, particularly in retrospective studies where material for expression profiling may not be available. The IHC pattern that best defines basal-like tumors is under investigation and various combinations of ER, PR, HER2-, CK5/6+ and EGFR+ have been tested. Methods Using datasets from two different hospitals we describe how using different combinations of immunohistochemical patterns has different effects on estimating prognosis at different time intervals after diagnosis. As our baseline, we used two IHC patterns ER-/PR-/HER2-("triple negative phenotype", TNP and ER-/HER2-/CK5/6+ and/or EGFR+ ("core basal phenotype", CBP. Results There was no overall difference in survival between the two hospital-based series, but there was a difference between the TNP and non-TNP groups which was most marked at 3 years (76.8% vs 93.5%, p Conclusion Our findings suggests that CK5/6 and/or EGFR expressing tumor types have a persistently poorer prognosis over the longer term, an observation that may have important therapeutic implications as drugs that target the EGFR are currently being evaluated in breast cancer.

  20. Myoepithelial carcinoma arising within an adenomyoepithelioma of the breast: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, You Yeon; Cho, Kyu Ran; Song, Sung Eun [Dept. of Radiology, Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Seo, Bo Kyoung [Dept. of Radiology, Ansan Hospital, Korea University College of Medicine, Ansan (Korea, Republic of); Woo, Ok Hee [Dept. of Radiology, Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Lee, Jeong Hyun [Dept. of Radiology, Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2017-07-15

    Adenomyoepithelioma of the breast is a rare tumor. A myoepithelial carcinoma arising within an adenomyoepithelioma is even more unusual. There are a limited number of reports discussing myoepithelial carcinoma; most of them describe pathological findings, but not imaging findings. We present a case of a 55-year-old woman who had a screen-detected myoepithelial carcinoma arising within an adenomyoepithelioma in her right breast. Upon the completion of a mammography and sonography an oval shaped mass with an indistinct margin in the upper portion of the right breast had been seen. It as appeared to be a spiculated, irregular-shaped, peripheral-enhancing mass on an MRI. On sonography-guided biopsy, an epithelial-myothelial tumor was confirmed, and the possibility of myoepithelial carcinoma was suggested. Breast-conserving surgery with a sentinel lymph node dissection was performed, and a pathological examination revealed a myoepithelial carcinoma arising within an adenomyoepithelioma.

  1. Comparison of Ultrasound Elastography and Color Doppler Ultrasonography for Distinguishing Small Triple-Negative Breast Cancer From Fibroadenoma.

    Science.gov (United States)

    Yeo, Soo Hyun; Kim, Ga Ram; Lee, Su Hyun; Moon, Woo Kyung

    2018-02-09

    To compare the performance of ultrasound elastography and color Doppler ultrasonography (US) in distinguishing small, oval, or round triple-negative breast cancer from fibroadenoma and the influence on the further management decision at US. In total, 131 biopsy-proven oval or round fibroadenomas (n = 68) and triple-negative breast cancers (n = 63) smaller than 2 cm were included. Three blinded readers assessed the images from US, elastography, and color Doppler imaging according to the Breast Imaging Reporting and Data System lexicon independently. Interobserver agreement was assessed, and sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve values for each data set were compared. Pathologic results were reference standards. The interobserver agreements were excellent (intraclass correlation coefficients, 0.856 for US, 0.948 for elastography, and 0.864 for color Doppler). The specificity and accuracy of US with elastography were increased compared with US alone or US with Doppler imaging without statistically significant differences in sensitivity. The average area under the curve for US with elastography (0.869) was increased compared with US alone (0.650) or US with color Doppler (0.576). Elastography is more useful than color Doppler imaging for distinguishing small, oval, or round triple-negative breast cancer from fibroadenoma, and elastography can help avoid biopsy of benign masses. © 2018 by the American Institute of Ultrasound in Medicine.

  2. Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Erika Guimarães

    Full Text Available Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10. In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.

  3. Leptomeningeal carcinomatosis can be presenting manifestation of breast carcinoma

    Directory of Open Access Journals (Sweden)

    Mandić-Stojmenović Gorana

    2016-01-01

    Full Text Available Introduction. Leptomeningeal carcinomatosis (LC is a serious complication occuring in solid cancer patients with rather poor prognosis. Case report. We presented a 47-yearold woman with the 6-month history of diffuse headache, nausea and visual obscuration. Initially, clinical status and brain magnetic resonance imaging (MRI indicated syndrome of idiopathic intracranial hypertension. Due to clinical progression and high papillary stasis, cerebrospinal fluid (CSF examination was performed only after ventriculoperitoneal shunt was implanted. This led to a significant although transient clinical improvement. Futher investigations led to the diagnosis of invasive lobular breast carcinoma and repeated CSF analysis revealed malignant breast carcinoma cells. In this case LC was an initial presentation of a malignant disease. Conclusion. In the presence of a high clinical suspicion of LC, in spite of initially negative findings, a clinician should persist in repeating relevant tests, such are MRI with larger amounts of gadolinium and high-volume cytological CSF analyses in order to make the diagnosis. [Projekat Ministarstva nauke Republike Srbije, br. 175022

  4. Genetic Alterations in Presumptive Precursor Lesions of Breast Carcinomas

    Directory of Open Access Journals (Sweden)

    Michaela Aubele

    2002-01-01

    Full Text Available The hypothetical multistep model of breast carcinogenesis suggests a transition from normal epithelium to invasive carcinoma via intraductal hyperplasia (without and with atypia and in situcarcinoma. These presumptive precursor lesions are currently defined by their histological features, and their prognosis is imprecisely estimated from indirect epidemiological evidence. Cytogenetic and molecular‐genetic analysis of these lesions give evidence for an accumulation of various genetic alterations during breast tumorigenesis. Using immuno‐histochemistry overexpression of the c‐erbB‐2 oncogene was found in ductal carcinoma in situ(DCIS, but not in atypical intraductal hyperplasia (AIDH and intraductal hyperplasia (IDH. An expression of mutant p53 tumor suppressor gene as well as expression of cyclin D1 was identified in DCIS. In IDH lesions loss of heterozygosity (LOH at various loci could be identified, and comparative genomic hybridization (CGH and fluorescence in situhybridization (FISH studies delivered evidence for DNA amplification on chromosomal region 20q13 in the early stage of IDH. However, little is currently known about genetic alterations in those premalignant lesions, and the chronology of genetic alterations and histopathological changes during carcinogenesis is mainly undiscovered. Figure 1 can be viewed in colour on http://www.esacp.org/acp/2002/24‐23/aubele.htm

  5. Inactivation of GPR30 reduces growth of triple-negative breast cancer cells: possible application in targeted therapy.

    Science.gov (United States)

    Girgert, Rainer; Emons, Günter; Gründker, Carsten

    2012-07-01

    Triple-negative breast cancers lack estrogen receptor α (ERα), progesterone receptor, and do not overexpress human epidermal growth factor receptor 2 (Her-2). They are neither susceptible to endocrine therapy nor to a therapy using the anti-Her-2 antibody, trastuzumab. Therefore, an efficient targeted therapy is warranted. Triple-negative breast tumors frequently express membrane bound estrogen receptor G-protein coupled receptor (GPR30). As proof of principle, we analyzed the consequences of a knock-down of GPR30 expression on the growth regulation of triple-negative breast cancer cell lines. Cells of triple-negative breast cancer cell lines were transfected with siRNA against GPR30 or control siRNA, and cell growth was stimulated either with 10(⁻⁹) M 17β-estradiol or 10(⁻⁶) M 4-hydroxytamoxifen. Cell proliferation was measured using Alamar blue staining. Activation of c-Src and epidermal growth factor (EGF)-receptor was assessed using western blot. Expression of c-fos was quantified by reverse transcription polymerase chain reaction. Seven days after transfection with siRNA, GPR30 mRNA in triple-negative breast cancer cell lines MDA-MB-435 and HCC1806 was reduced by 74 and 90%, respectively. 10(⁻⁸) M 17β-estradiol enhanced proliferation of MDA-MB-435 to 129.6±5.4% of control (pcell number of MDA-MB-435 to 121.0±6.9% of control (pproliferation by the two estrogenic compounds was completely prevented by knock-down of GPR30 expression in both cell lines. In control cells, activity of Src kinase was increased 3-fold by estradiol and 3.8-fold using 4-hydroxytamoxifen. Transactivation of the EGF-receptor was similarly increased in both cell lines by 17β-estradiol and 4-hydroxytamoxifen. Both compounds increased c-fos expression 1.5- and 3.1-fold, respectively. Knock-down of GPR30 expression completely abolished activation of all these signaling pathways responsible for enhanced proliferation. A pharmacological inhibition of GPR30 by specific small

  6. Histopathological and clonal study of combined lobular and ductal carcinoma of the breast

    Science.gov (United States)

    Tazaki, Eri; Shishido-Hara, Yukiko; Mizutani, Natsuko; Nomura, Sachiyo; Isaka, Hirotsugu; Ito, Hiroki; Imi, Kentaro; Imoto, Shigeru; Kamma, Hiroshi

    2013-01-01

    Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty-two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re-examination using immunostain of E-cadherin and β-catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation-specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways. PMID:23782331

  7. Combination of triple biomarkers AFP, AFP-L3, and PIVAKII for early detection of hepatocellular carcinoma in China: Expectation.

    Science.gov (United States)

    Gao, Jianjun; Song, Peipei

    2017-01-01

    Hepatocellular carcinoma (HCC) remains a severe health threat in China. Early tumor detection is crucial for improving the prognosis of patients. Currently, ultrasound plus biomarker alpha fetoprotein (AFP) is recommended by Chinese Liver Cancer Diagnosis and Treatment Guidelines in China. However, most HCC continues to be diagnosed beyond an early stage due to insufficient sensitivity and specificity of current surveillance tools, highlighting the need for more accurate biomarkers to improve early HCC detection. In Japan, ultrasound plus triple biomarkers AFP, Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and prothrombin induced by vitamin K absence II (PIVKA II) has been routinely used for HCC surveillance and achieved increased early HCC detection rate. Very recently, the assay of triple biomarkers AFP, AFP-L3, and PIVKA II using μTASWako i30 immuno-analyzer was brought into China. The prospect of the modality of ultrasound plus triple biomarkers for early HCC detection in China is expected in the future.

  8. A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

    Science.gov (United States)

    Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

    2017-03-01

    Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

  9. Class distribution of immunoglobulin-containing plasma cells in the stroma of medullary carcinoma of breast.

    Science.gov (United States)

    Ito, T; Saga, S; Nagayoshi, S; Imai, M; Aoyama, A; Yokoi, T; Hoshino, M

    1986-01-01

    A class distribution of plasma cells associated with the stroma in twenty-eight cases of medullary carcinoma of the breast was investigated by an unlabeled immunoperoxidase method. The stroma of the medullary carcinomas tested was found to contain predominantly IgG plasma cells except in two cases. Stroma of the other types of breast carcinoma, including ten cases of papillo-tubular carcinoma, five cases of scirrhous carcinoma, and six cases of medullary tubular carcinoma, contained predominantly IgG plasma cells, although few plasma cells were associated with carcinoma tissues in the latter group. Plasma cells associated with control specimens, including normal breast, fibroadenoma, cystic disease, and intraductal papilloma, were found to be predominantly of IgA type. Few carcinomatous epithelial cells contained secretory components in the cytoplasm, while a number of cells positive for secretory components were observed in acinar and ductular epithelia of normal breast tissues and in benign proliferative lesions of the breast. It is suggested that the lymphoid cells infiltrating the stroma of medullary carcinoma represent a sign of host immune response against the carcinoma cells which is related to the well-known favorable prognosis associated with this tumor.

  10. Expression of ERβ gene in breast carcinoma and the relevance in neoadjuvant therapy.

    Science.gov (United States)

    Chang, Jing; Liu, Jihong; Li, Huiying; Li, Jing; Mu, Yanling; Feng, Bin

    2017-03-01

    In the present study, we examined the expression of the estrogen receptor β (ERβ) gene in breast cancer and its relevance in neoadjuvant therapy. In total, 120 breast cancer patients who were hospitalized in the Departments of Breast Disease and Medical Oncology served as the subjects of this study. The subjects were diagnosed with breast cancer phase II to phase IIIA, as confirmed by aspiration biopsy and iconography. The patients were divided into two groups in a randomized control manner, with 60 patients in each group. The experimental group was administered the taxotere + epirubicin + cyclophosphamide (TEC) plan for 3-4 cycles of chemotherapy before the modified radical operation of breast cancer. In the control group, no TEC chemotherapy was carried out prior to operation. Instead, the breast lesion was removed directly by operation. After the operation, the IHC method was used to stain the ERβ protein in the lesion tissue. The patients were classified according to whether the basement membrane was broken through; 5 cases had non-infiltrative carcinoma and 115 cases had infiltrative carcinoma. According to the pathology of the lesion, 114 cases had breast ductal carcinoma, 2 cases had mucinous breast carcinoma (of which there were 2 cases combined with ductal carcinoma), and 4 cases had breast lobular carcinoma. The ERβ gene was found to be expressed in normal and breast cancer tissues. When ERβ gene expression was compared before and after the chemotherapy, its expression was significantly increased in breast cancer tissues, which shows a significant statistical difference (Pgene in carcinoma tissue was significantly lower than that in the control group, and differences were statistically significant (Pgene in breast carcinoma tissues was high. The application of adjuvant chemotherapy before the modified radical operation for breast carcinoma can significantly lower the level of ERβ expression. The expression levels of ERβ gene in the carcinoma tissue

  11. Featured Article: Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells

    Science.gov (United States)

    Huang, Ou; Zhang, Weili; Zhi, Qiaoming; Xue, Xiaofeng; Liu, Hongchun; Shen, Daoming; Geng, Meiyu; Xie, Zuoquan

    2015-01-01

    Triple-negative breast cancer (TNBC) is defined as a group of primary breast cancers lacking expression of estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate and lower survival compared with other subtypes. Due to lack of identified targets and molecular heterogeneity, conventional chemotherapy is the only available option for treatment of TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that these TNBC cells were sensitive to teriflunomide, which was a well-known immunomodulatory drug for treatment of relapsing multiple sclerosis (MS). Potent anti-cancer effects in TNBC in vitro, including proliferation inhibition, cell cycle delay, cell apoptosis, and suppression of cell motility and invasiveness, could be achieved with this agent. Of note, we showed that multiple signals involved in TNBC proliferation, survival, migratory, and invasive potential were under regulation by teriflunomide. Among them, we identified down-regulation of growth factor receptors to abolish growth maintenance, suppression of c-Myc, and cyclin D1 to contribute to its anti-proliferative effect, modulation of components of cell cycle to induce S-phase arrest, degradation of Bcl-xL, and up-regulation of BAX via activation of MAPK pathway to induce apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) process, matrix metalloproteinase-9 (MMP9) expression, and inactivation of Src/FAK to reduce TNBC migration and invasion. The results identified teriflunomide may be of therapeutic benefit for the more aggressive and difficult-to-treat breast cancer subtype, indicating the use of teriflunomide for clinical trials for treatment of TNBC patients. PMID:25304315

  12. Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells.

    Science.gov (United States)

    Huang, Ou; Zhang, Weili; Zhi, Qiaoming; Xue, Xiaofeng; Liu, Hongchun; Shen, Daoming; Geng, Meiyu; Xie, Zuoquan; Jiang, Min

    2015-04-01

    Triple-negative breast cancer (TNBC) is defined as a group of primary breast cancers lacking expression of estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate and lower survival compared with other subtypes. Due to lack of identified targets and molecular heterogeneity, conventional chemotherapy is the only available option for treatment of TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that these TNBC cells were sensitive to teriflunomide, which was a well-known immunomodulatory drug for treatment of relapsing multiple sclerosis (MS). Potent anti-cancer effects in TNBC in vitro, including proliferation inhibition, cell cycle delay, cell apoptosis, and suppression of cell motility and invasiveness, could be achieved with this agent. Of note, we showed that multiple signals involved in TNBC proliferation, survival, migratory, and invasive potential were under regulation by teriflunomide. Among them, we identified down-regulation of growth factor receptors to abolish growth maintenance, suppression of c-Myc, and cyclin D1 to contribute to its anti-proliferative effect, modulation of components of cell cycle to induce S-phase arrest, degradation of Bcl-xL, and up-regulation of BAX via activation of MAPK pathway to induce apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) process, matrix metalloproteinase-9 (MMP9) expression, and inactivation of Src/FAK to reduce TNBC migration and invasion. The results identified teriflunomide may be of therapeutic benefit for the more aggressive and difficult-to-treat breast cancer subtype, indicating the use of teriflunomide for clinical trials for treatment of TNBC patients. © 2014 by the Society for Experimental Biology and Medicine.

  13. Germline mutations in DNA repair genes may predict neoadjuvant therapy response in triple negative breast patients.

    Science.gov (United States)

    Spugnesi, Laura; Gabriele, Michele; Scarpitta, Rosa; Tancredi, Mariella; Maresca, Luisa; Gambino, Gaetana; Collavoli, Anita; Aretini, Paolo; Bertolini, Ilaria; Salvadori, Barbara; Landucci, Elisabetta; Fontana, Andrea; Rossetti, Elena; Roncella, Manuela; Naccarato, Giuseppe Antonio; Caligo, Maria Adelaide

    2016-12-01

    Triple negative breast cancers (TNBCs) represent about 15-20% of all breast cancer cases and are characterized by a complex molecular heterogeneity. Some TNBCs exhibit clinical and pathological properties similar to BRCA-mutated tumors, without actually bearing a mutation in BRCA genes. This "BRCAness" phenotype may be explained by germline mutations in other genes involved in DNA repair. Although respond to chemotherapy with alkylating agents, they have a high risk of recurrence and progression. Some studies have shown the efficacy of neoadjuvant therapy in TNBC patients with DNA repair defects, but proper biomarkers of DNA repair deficiency are still needed. Here, we investigated if mutations in DNA repair genes may be correlated with anthracyclines/taxanes neoadjuvant therapy response. DNA from 19 TNBC patients undergoing neoadjuvant therapy were subjected to next generation sequencing of a panel of 24 genes in DNA repair and breast cancer predisposition. In this study, 5 of 19 patients (26%) carried a pathogenic mutation in BRCA1, PALB2, RAD51C and two patients carried a probable pathogenic missense variant. Moreover, VUS (Variants of Unknown Significance) in other genes, predicted to be deleterious by in silico tools, were detected in five patients. Germline mutations in DNA repair genes were found to be associated with the group of TNBC patients who responded to therapy. We conclude that a subgroup of TNBC patients have defects in DNA repair genes, other than BRCA1, and such patients respond favourably to neoadjuvant anthracyclines/taxanes therapy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Epigenetic silencing of triple negative breast cancer hallmarks by Withaferin A

    Science.gov (United States)

    vel Szic, Katarzyna Szarc; Declerck, Ken; Crans, René A.J; Diddens, Jolien; Scherf, David B.; Gerhäuser, Clarissa; Berghe, Wim Vanden

    2017-01-01

    Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2’-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3). Gene expression and pathway enrichment analysis further reveals epigenetic suppression of multiple cancer hallmarks associated with cell cycle regulation, cell death, cancer cell metabolism, cell motility and metastasis. Remarkably, DNA hypermethylation of corresponding CpG sites in PLAU, ADAM8, TNSF12, GSTM1 and ME3 genes correlates with receptor tyrosine-protein kinase erbB-2 amplification (HER2)/estrogen receptor (ESR)/progesterone receptor (PR) status in primary BC tumors. Moreover, upon comparing differentially methylated WA responsive target genes with DNA methylation changes in different clinical subtypes of breast cancer patients in the cancer genome atlas (TCGA), we found that WA silences HER2/PR/ESR-dependent gene expression programs to suppress aggressive TNBC characteristics in favor of luminal BC hallmarks, with an improved therapeutic sensitivity. In this respect, WA may represent a novel and attractive phyto-pharmaceutical for TNBC treatment. PMID:28467815

  15. Prostate-specific antigen and hormone receptor expression in male and female breast carcinoma

    Directory of Open Access Journals (Sweden)

    Cohen Cynthia

    2010-09-01

    Full Text Available Abstract Background Prostate carcinoma is among the most common solid tumors to secondarily involve the male breast. Prostate specific antigen (PSA and prostate-specific acid phosphatase (PSAP are expressed in benign and malignant prostatic tissue, and immunohistochemical staining for these markers is often used to confirm the prostatic origin of metastatic carcinoma. PSA expression has been reported in male and female breast carcinoma and in gynecomastia, raising concerns about the utility of PSA for differentiating prostate carcinoma metastasis to the male breast from primary breast carcinoma. This study examined the frequency of PSA, PSAP, and hormone receptor expression in male breast carcinoma (MBC, female breast carcinoma (FBC, and gynecomastia. Methods Immunohistochemical staining for PSA, PSAP, AR, ER, and PR was performed on tissue microarrays representing six cases of gynecomastia, thirty MBC, and fifty-six FBC. Results PSA was positive in two of fifty-six FBC (3.7%, focally positive in one of thirty MBC (3.3%, and negative in the five examined cases of gynecomastia. PSAP expression was absent in MBC, FBC, and gynecomastia. Hormone receptor expression was similar in males and females (AR 74.1% in MBC vs. 67.9% in FBC, p = 0.62; ER 85.2% vs. 68.5%, p = 0.18; and PR 51.9% vs. 48.2%, p = 0.82. Conclusions PSA and PSAP are useful markers to distinguish primary breast carcinoma from prostate carcinoma metastatic to the male breast. Although PSA expression appeared to correlate with hormone receptor expression, the incidence of PSA expression in our population was too low to draw significant conclusions about an association between PSA expression and hormone receptor status in breast lesions.

  16. Radiographic features of invasive lobular carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Uchiyama, Nachiko; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan); Miyakawa, Kunihisa; Moriyama, Noriyuki

    2001-02-01

    The purpose of this study was to evaluate the radiographic features of invasive lobular carcinoma of the breast. We evaluated the radiographic features of 61 cases of histopathologically documented invasive lobular carcinoma. Mammography was performed in all cases. In seven of 61 cases, helical CT with contrast medium was also carried out. Mammographic findings were analyzed to determine true-positive and false-negative rates for the detection of neoplasm. Further, the diameter of the tumor as determined on mammography and helical CT was noted for comparison with the pathologic size. Mammographic features were divided into six types: spiculated mass (38%), indistinct mass (5%), obscured mass (23%), asymmetric opacity (16%), architectural distortion (16%), and no findings (2%). Microcalcifications were present in 12 cases (20%). The overall sensitivity rate was 59%. However, 20 (56%) of 36 cases that were diagnosed as detectable on mammography were underestimated in terms of tumor size compared with the histopathologic findings. Four cases examined by helical CT with contrast medium were compared with the histopathologic findings in terms of extent of the lesion. In three cases, helical CT was more precise than mammography, but the histopathologic findings showed lesions beyond the region evaluated by helical CT. Invasive lobular carcinoma is difficult to detect radiographically, and the extent of the lesion tends to be underestimated. (author)

  17. Expression and significance of EZH2 and DNMT1 in triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Ping-ping WU

    2015-04-01

    Full Text Available Objective To probe into the expression features of EZH2 and DNMT1 in triple-negative breast cancer (TNBC, and the relations between the expression and the main clinical pathological parameters of TNBC. Methods The clinical and pathological data of 209 cases of breast cancer (including 131 cases of TNBC and 78 cases of non-TNBC in Guangzhou Kingmed Center for Clinical Laboratory from Jan. 2008 to May 2013 were retrospectively analyzed. Immunohistochemistry SP assay was performed to determine the expressions of EZH2 and DNMT1 in 209 paraffin-embedded specimens of breast cancer and 65 specimens of normal tissue (more than 4cm away from tumor. The differences of protein expression in the specimens were compared, and correlation analysis was performed to disclose the relationship between protein expression and clinico-pathological indices. Multivariate logistic regression analysis was applied to analyze the positive expression-related factor of EZH2 and DNMT1. Spearman rank correlation analysis was used to analyse the interrelation of EZH2 and DNMT1 in TNBC. Results The positive expression rates of EZH2 in TNBC, non-TNBC and adjacent breast tissue were 86.3%, 89.7% and 40.0%, respectively, while the positive expression rates of DNMT1 were 63.4%, 66.6% and 44.6%, respectively. The positive expression rates of EZH2 and DNMT1 were higher in both TNBC and non-TNBC tissues than in adjacent breast tissue (P0.05, but the positive expression of EZH2 in TNBC was related to the pathological grade, tumor size and lymph node metastasis (P<0.05, and the positive expression of DNMT1 was related to the pathological grade and lymph node metastasis (P<0.05. Multivariate logistic regression analysis demonstrated that the pathological grade of tumor was the main factor affecting the expressions of EZH2 and DNMT1, and the expressions of EZH2 and DNMT1 in TNBC were positively correlated (r=0.34, P<0.01. Conclusion The high expressions of EZH2 and DNMT1 are

  18. Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez).

    Science.gov (United States)

    Akasbi, Yousra; Bennis, Sanae; Abbass, Fouad; Znati, Kawtar; Joutei, Khalid Amrani; Amarti, Afaf; Mesbahi, Omar El

    2011-11-16

    Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR) and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-).The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer. This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome. A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients), 12.6% were basal-like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like). Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like). For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes.The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS). TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple negative disease, and adequately powered prospective TNBC trials to

  19. Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez

    Directory of Open Access Journals (Sweden)

    Akasbi Yousra

    2011-11-01

    Full Text Available Abstract Introduction Triple-negative breast cancer (TNBC is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK 5/6+ and/or Her1+ and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-. The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer. Methods This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome. Results A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients, 12.6% were basal-like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like. Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like. For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes. The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS. Conclusion TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple

  20. Genetic predisposition to ductal carcinoma in situ of the breast.

    Science.gov (United States)

    Petridis, Christos; Brook, Mark N; Shah, Vandna; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Levi, Dina; Papouli, Efterpi; Orr, Nick; Cox, Angela; Cross, Simon S; Dos-Santos-Silva, Isabel; Peto, Julian; Swerdlow, Anthony; Schoemaker, Minouk J; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Benitez, Javier; González-Neira, Anna; Tessier, Daniel C; Vincent, Daniel; Li, Jingmei; Figueroa, Jonine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Soucy, Penny; Simard, Jacques; Milne, Roger L; Giles, Graham G; Margolin, Sara; Lindblom, Annika; Brüning, Thomas; Brauch, Hiltrud; Southey, Melissa C; Hopper, John L; Dörk, Thilo; Bogdanova, Natalia V; Kabisch, Maria; Hamann, Ute; Schmutzler, Rita K; Meindl, Alfons; Brenner, Hermann; Arndt, Volker; Winqvist, Robert; Pylkäs, Katri; Fasching, Peter A; Beckmann, Matthias W; Lubinski, Jan; Jakubowska, Anna; Mulligan, Anna Marie; Andrulis, Irene L; Tollenaar, Rob A E M; Devilee, Peter; Le Marchand, Loic; Haiman, Christopher A; Mannermaa, Arto; Kosma, Veli-Matti; Radice, Paolo; Peterlongo, Paolo; Marme, Frederik; Burwinkel, Barbara; van Deurzen, Carolien H M; Hollestelle, Antoinette; Miller, Nicola; Kerin, Michael J; Lambrechts, Diether; Floris, Giuseppe; Wesseling, Jelle; Flyger, Henrik; Bojesen, Stig E; Yao, Song; Ambrosone, Christine B; Chenevix-Trench, Georgia; Truong, Thérèse; Guénel, Pascal; Rudolph, Anja; Chang-Claude, Jenny; Nevanlinna, Heli; Blomqvist, Carl; Czene, Kamila; Brand, Judith S; Olson, Janet E; Couch, Fergus J; Dunning, Alison M; Hall, Per; Easton, Douglas F; Pharoah, Paul D P; Pinder, Sarah E; Schmidt, Marjanka K; Tomlinson, Ian; Roylance, Rebecca; García-Closas, Montserrat; Sawyer, Elinor J

    2016-02-17

    Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

  1. Her-2 neu negative lipid rich breast carcinoma in an immunocompromised patient

    Directory of Open Access Journals (Sweden)

    Deepika Sirohi, M.D.

    2015-12-01

    Full Text Available Lipid-rich breast carcinoma (LRBC is rare cancer considered to be a variant of invasive ductal breast carcinoma. It is characterized by an aggressive behavior and poor prognosis and requires prompt recognition and close follow-up. The tumor derives its name from the intracytoplasmic neutral lipid that gives it a vacuolated appearance and is included in the current WHO classification. We report here a case of Her-2 neu negative lipid-rich carcinoma of the breast occurring in a HIV positive woman.

  2. An Unusual Case of Locally Advanced Glycogen-Rich Clear Cell Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Beatriz Martín-Martín

    2011-09-01

    Full Text Available Glycogen-rich clear cell (GRCC is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC. The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months’ follow-up.

  3. Biliary Dyskinesia as a Rare Presentation of Metastatic Breast Carcinoma of the Gallbladder: A Case Report

    Directory of Open Access Journals (Sweden)

    A. Markelov

    2011-01-01

    Full Text Available Background. Breast carcinoma is the most common malignancy in women worldwide. It is most commonly associated with metastases to the liver, lung, bone, and the brain. Invasive lobular carcinoma is a less common pathology with slightly higher metastases to the upper gastrointestinal tract. Invasive lobular carcinoma metastasis to the gallbladder is extremely rare. Method. In this paper we are presenting a case of a 67-year-old female with metastases of invasive lobular breast cancer to the gallbladder six years after her therapy. Conclusion. This case clearly signifies the nature of the micrometastatic foci of the invasive lobular carcinoma even many years after a successful treatment.

  4. The Shrinking Breast: An Unusual Mammographic Finding of Invasive Lobular Carcinoma.

    Science.gov (United States)

    Jafri, Nazia F; Slanetz, Priscilla J

    2007-01-01

    We report two cases of invasive lobular carcinoma of the breast that were initially missed on first mammographic interpretation because of an uncommon, easily overlooked, and unreported imaging presentation. The abnormality in the cases manifested as an apparent decrease in breast glandular tissue volume when compared with the patients' previous mammograms, observed as "shrinking" of the breast on mammography. Invasive lobular carcinoma is considered one of the most difficult subtypes of breast cancer to identify on mammography because the changes that occur are often nonspecific and subtle. Microcalcifications that are usually associated with breast masses on imaging are rarely seen in this subtype of breast cancer. Although magnetic resonance imaging and computer-aided detection have somewhat improved the detection of invasive lobular carcinoma, radiologic and clinical detection remains a challenge.

  5. Oral Metastasis of Metaplastic Breast Carcinoma in a Patient with Neurofibromatosis 1

    Directory of Open Access Journals (Sweden)

    Ana Paula Molina Vivas

    2014-01-01

    Full Text Available Neurofibromatosis type 1 (NF1 has been associated with an increased risk for development of malignancy, especially malignant peripheral nerve sheath tumors. In addition, recently, literature has demonstrated an increased risk of breast cancer in women with NF1. The present paper shows a 53-year-old woman with NF1 who presented with metaplastic breast carcinoma and developed multiple metastases, including mandible. Furthermore, we reviewed the English literature, found 63 cases showing the association between NF1 and breast cancer, and added one more case. The present study demonstrated an important association between NF1 and breast cancer. Until the present time, there has been only one case of metaplastic breast carcinoma associated with NF1. Curiously, in our case the oral metastasis corresponded to sarcomatous component of metaplastic breast carcinoma.

  6. A case of adenoid cystic carcinoma of the breast.

    Science.gov (United States)

    Ichikawa, Katsuhiro; Mizukami, Yuji; Takayama, Teruhiko; Takemura, Akihiro; Miyati, Tosiaki; Taniya, Takao

    2007-12-01

    A 57-year-old woman was referred to our institution 4 months after she noticed a palpable, painless mass in her left breast. Physical examination revealed a mobile and elastic mass. An axillary or subclavicular lymph node was not palpable. Mammography revealed a lobulated mass with a partially ill-defined border. Ultrasonography depicted a 2.5 × 1.5 cm irregularly shaped mass with heterogeneous internal echo and posterior acoustic enhancement. The border of the mass was poorly defined at the anterior and lateral aspects of the mass. Results of ultrasonography-guided fine-needle aspiration cytology were strongly suggestive of a malignant tumor. Thus, the patient underwent breast-conserving surgery with axillary lymph node dissection. The gross resected specimen revealed a gray-to-white and well-demarcated solid tumor measuring 3 × 2 × 2.5 cm, with an irregular border and heterogeneous internal structure. Histological examination showed the characteristic patterns of adenoid cystic carcinoma of the breast. Immunohistochemical studies for both estrogen receptors (ER) and progesterone receptors (PgR) were negative. The patient remains well and has no clinical recurrence of the disease after 5 years of follow-up without radiotherapy or adjuvant therapy.

  7. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Gurkan Yetkin

    2017-01-01

    Full Text Available A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.

  8. Pleomorphic Lobular Carcinoma of the Breast: Clinicopathological Analysis of a Distinctive and Rare Variant of Lobular Carcinoma

    Directory of Open Access Journals (Sweden)

    Olfa El Amine

    2016-12-01

    Full Text Available Pleomorphic lobular carcinoma (PLC of the breast is an uncommon variant of invasive lobular carcinoma (ILC, accounting for 0.67% of all breast carcinomas and <5% of lobular carcinoma. This lesion is usually misdiagnosed as infiltrating ductal carcinoma. It has been identified as a distinct entity from classic ILC and is reported to be associated with a more aggressive clinical behavior than classic lobular carcinoma. In this report, we aim to describe radiological and pathological characteristics of PLC and to review the therapeutic management. We present a new case of PLC occurring in a 74-year-old woman, consulting for a retro-areolar mass in the right breast, measuring 3 cm in great diameter. She underwent a mastectomy. The tumor was described as PLC. Radiologically, the PLC is most commonly similar to invasive ductal carcinoma. It is described as a speculated mass on mammography or ultrasonography. However, unlike the classic variant, the tumor cells of the pleomorphic variant of ILC are larger and have abundant cytoplasm with large hyperchromatic nuclei that show prominent nucleoli. Positivity for hormone receptors and amplification of human epidermal growth factor-2/neu in PLC suggest that endocrine-related targeted therapy and trastuzumab may be valuable treatment regimens for these patients. [J Interdiscipl Histopathol 2016; 4(4.000: 104-106

  9. Breast biopsy with wire localization: factors influencing complete excision of nonpalpable carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Besic, N.; Zgajnar, J.; Hocevar, M.; Snoj, N.; Lindtner, J. [Department of Surgical Oncology, Institute of Oncology, Zaloska 2, 1000 Ljubljana (Slovenia); Rener, M. [Department of Radiology, Institute of Oncology, Zaloska 2, 1000 Ljubljana (Slovenia); Frkovic-Grazio, S. [Department of Pathology, Institute of Oncology, Zaloska 2, 1000 Ljubljana (Slovenia)

    2002-11-01

    Our aim was to find out the factors influencing the complete excision of nonpalpable carcinoma. During a 2-year period, 215 patients (median age 55 years) underwent biopsy after wire localization of 222 nonpalpable breast lesions. Mammographic, surgical and pathological factors were correlated with the outcome of surgery using contingence tables in SPSS statistical software. A total of 96 carcinomas were diagnosed: 38 in situ and 58 invasive carcinomas. Surgical margins were clear in 43, close in 20 and involved in 33 cases. Factors correlated with clear surgical margins are mammographically spicular lesion, cytologically proven carcinoma, excision of more than 50 g of tissue, carcinoma smaller than 10 mm, invasive carcinoma without in situ component, and unicentric ductal carcinoma in situ (p<0.05). Complete excision of multifocal in situ carcinoma or invasive carcinoma with extensive in situ component, which are diagnosed on mammogram as suspicious microcalcifications, remains a puzzling surgical task. (orig.)

  10. Lymphoepithelioma-like carcinoma of breast-evaluation for Epstein-Barr virus-encoded RNA, human papillomavirus, and markers of basal cell differentiation.

    Science.gov (United States)

    Shet, Tanuja; Pai, Trupti; Shetty, Omshree; Desai, Sangeeta

    2016-12-01

    This is a largest series of 5 cases of lymphoepithelioma-like carcinoma (LEC) of the breast attempting to look at the expression of basal cytokeratins (CKs), human papillomavirus, and Epstein-Barr virus-encoded RNAs in these tumors. Five cases were selected after stringent evaluation of all breast carcinomas showing dense lymphoid infiltration. Histologically, all these tumors showed the typical histology except 1 tumor that showed an unusual granulomatous response. All tumors were negative for estrogen and progesterone receptors and HER2 (triple negative). Three tumors expressed CK5/6 and high-molecular-weight CK, whereas only the case with nodal metastasis expressed CK14. Analysis for in situ hybridization for Epstein-Barr virus-encoded RNAs and human papillomavirus DNA on paraffin-processed tissues was negative in all tumors. All of these patients received adjuvant therapy. One patient with tumor expressing basal marker, CK5/6, had contralateral breast malignancy after a duration of 53 months of treatment completion. The rest were disease free with the follow-up period in the range of 6 to 105 months. The lymphoepithelioma-like carcinoma of breast expressed basal CK profile that is more CK5/6 positive than CK14. Analysis of basal markers within these tumors may help in refining the definition of these tumors and in classifying them into prognostically relevant groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Role of surgery in breast metastasis from carcinoma of the cervix

    Directory of Open Access Journals (Sweden)

    Parveen Yadav

    2011-01-01

    Full Text Available Carcinoma of the cervix is the most common malignancy among women in India. Although metastatic disease is common, metastasis to breast is rare. A limited number of case reports are published in the world literature. Most of the previous reports of metastatic cervical carcinoma to breast are either autopsy series or widely disseminated disease where no treatment options were available. A rare case of cervical carcinoma presenting as metastasis in breast is reported here where palliative mastectomy improved the general condition of the patient. A female patient aged 58 years was diagnosed and treated for cervical carcinoma, FIGO stage 2B. Four months after the treatment which included both external beam and intracavitory radiotherapy, the patient presented with breast and lung metastasis. Palliative mastectomy was done which improved the general condition of the patient. Metastatic carcinoma of the cervix can present as a case of breast carcinoma. In an appropriate setting, this possibility should be kept in mind. Palliative mastectomy should be offered for patients of cervical carcinoma with metastasis to breast when needed.

  12. MiR-34b is associated with clinical outcome in triple-negative breast cancer patients

    Directory of Open Access Journals (Sweden)

    Svoboda Marek

    2012-03-01

    Full Text Available Abstract Background Breast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC represents the major phenotype of basal-like molecular subtype of breast cancer, characterized by higher incidence in young women and a very poor prognosis. MicroRNAs (miRNAs are small non-coding RNAs playing significant role in the pathogenesis of many cancers including breast cancer. Therefore, miRNAs are also potential prognostic and/or predictive biomarkers in triple-negative breast cancer patients. Methods Thirty-nine TNBC patients with available formalin-fixed paraffin-embedded (FFPE tissues were enrolled in the study. MiR-34a, miR-34b, and miR-34c were analyzed using qRT-PCR and correlated to clinico-pathological features of TNBC patients. Results Expression levels of miR-34b significantly correlate with disease free survival (DFS (p = 0.0020, log-rank test and overall survival (OS (p = 0.0008, log-rank test of TNBC patients. No other significant associations between miR-34a, miR-34b, and miR-34c with available clinical pathological data were observed. Conclusions MiR-34b expression negatively correlates with disease free survival and overall survival in TNBC patients. Thus, miR-34b may present a new promising prognostic biomarker in TNBC patients, but independent validations are necessary.

  13. Invasive lobular carcinoma of the breast with extracellular mucin: A case report.

    Science.gov (United States)

    Gómez Macías, G S; Pérez Saucedo, J E; Cardona Huerta, S; Garza Montemayor, M; Villarreal Garza, C; García Hernández, I

    2016-01-01

    Invasive lobular carcinoma is the second most common histological type of breast carcinoma, accounting for approximately 5%-15% of all invasive breast cancers. The extracellular mucin secretion is by default a feature of ductal carcinoma. Only four cases of infiltrative lobular carcinoma with extracellular mucin have been report. A 60 year old female asymptomatic patient with palpable breast mass and architectural distortion by mammography on external upper quadrant of the right breast was diagnosed as invasive lobular carcinoma with extracellular mucin in the resection, confirmed with immunohistochemistry markers. Previous report in the literature of four cases of Invasive lobular carcinoma of breast with extracellular mucin, all of them sharing the same histologic features: the presence of extracellular and intracellular mucin with appearance of infiltrates lobular carcinoma with signet ring cells and "Indian files". It is important to know that extracellular mucin production is not exclusive of ductal lesions and keep in mind the lobular carcinomas with extracellular mucin as a differential diagnosis. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Metastatic nonpalpable invasive lobular breast carcinoma presenting as rectal stenosis: a case report.

    Science.gov (United States)

    Osaku, Tadatoshi; Ogata, Hideaki; Magoshi, Shunsuke; Kubota, Yorichika; Saito, Fumi; Kanazawa, Shinsaku; Kaneko, Hironori

    2015-04-24

    Invasive lobular carcinomas have an increased propensity for distant metastases, particularly to the peritoneum, ovaries, and uterus. In contrast, distant metastases of nonpalpable lobular carcinomas are extremely rare, and the causes of underlying symptoms of primary carcinomas remain unclear. We report a case of an asymptomatic invasive lobular carcinoma with a primary mammary lesion in a patient with rectal stenosis. A 69-year-old Japanese woman presented to our hospital for treatment of constipation. Although rectal stenosis was confirmed, thorough testing of her lower digestive tract did not identify its cause. Thus, an exploratory laparotomy and tissue biopsy was performed, and the presence of an invasive lobular carcinoma was confirmed. Subsequent breast examinations showed that the invasive lobular carcinoma that led to the rectal stenosis was a metastatic lesion from a primary lesion of the breast duct. As the present breast lobular carcinoma was asymptomatic and nonpalpable, we did not initially consider metastatic breast cancer as a cause of her symptoms, and the final diagnosis was delayed. Peritoneal metastasis from nonpalpable invasive lobular carcinomas is very rare. However, breast cancer metastasis should be considered when carcinomatous peritonitis is present in a patient with an unknown primary cancer.

  15. Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer

    OpenAIRE

    Kim, Ji Young; Lee, Hyebin; Woo, Jongmin; Yue, Wang; Kim, Kwangsoo; Choi, Seongmin; Jang, Ja-June; Kim, Youngsoo; Park, In Ae; Han, Dohyun; Ryu, Han Suk

    2017-01-01

    Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alteratio...

  16. A Novel Differentiation Therapy Approach to Reduce the Metastatic Potential of Basal, Highly Metastatic, Triple-Negative Breast Cancers

    Science.gov (United States)

    2012-05-01

    metastases by GATA3 results from the suppression of lysyl oxidase (LOX) expression, a metastasis promoting matrix remodeling protein, via epigenetic changes...TERMS GATA3, Lysyl oxidase , triple-negative breast cancer, metastasis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...macrophages promoting metastatic progression. Importantly, we demonstrate that the repression of lysyl oxidase (LOX) expression by GATA3 is a key

  17. Novel Functions of EZH2 in Triple Negative Breast Cancer: Translation in to New Biomarker and Treatment Strategies

    Science.gov (United States)

    2016-07-01

    Translation into New Biomarker and Treatment Strategies 5b. GRANT NUMBER Bc140965 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Celina G. Kleer, M.D...1 AWARD NUMBER: W81XWH-15-1-0019 TITLE: Novel Functions of EZH2 in Triple Negative Breast Cancer: Translation in to New Biomarker and...Treatment Strategies . PRINCIPAL INVESTIGATOR: Celina G. Kleer, M.D. CONTRACTING ORGANIZATION: University of Michigan Ann Arbor, MI 48109 REPORT DATE

  18. Significance of alpha 9 beta 1 and alpha v beta 6 integrin expression in breast carcinoma.

    Science.gov (United States)

    Arihiro, K; Kaneko, M; Fujii, S; Inai, K; Yokosaki, Y

    2000-01-01

    Both alpha 9 beta 1 and alpha v beta 6 integrins have been newly identified from the tracheal epithelium of guinea pig. It has been pointed out that alpha 9 beta 1 functions as a receptor for tenascin-C and osteopontin. As for the ligands of alpha v beta 6, fibronectin and tenascin-C have been identified. It has not been ascertained whether alpha 9 beta 1 and alpha v beta 6 are expressed in normal breast tissue, benign breast lesion or breast carcinoma. Immunohistochemical staining for alpha 9 beta 1 and alpha v beta 6 was performed in benign breast lesion and breast carcinoma specimens. Western blotting was carried out on 11 breast carcinoma cases. alpha 9 beta 1 was expressed in the cytoplasm of carcinoma cells in 23 of 90 cases (26%) and alpha v beta 6 in the membrane of carcinoma cells in 16 of 90 cases (18%). However, these findings of alpha 9 beta 1 and alpha v beta 6 did not correlate with any clinicopathological factors including the patients' age, tumor size, histological type of carcinoma, location of carcinoma cells and hormone receptor status. With regard to the histological grade of carcinoma, alpha v beta 6 and alpha 9 beta 1 expression did not statistically correlate, although no expression of alpha v beta 6 was observed in 14 cases of Grade I. On Western-blott analysis strong and weak bands consistent with alpha v beta 6 were noted in the membrane fraction extracted from breast carcinoma cells. On the other hand weak bands consistent with alpha 9 subunit were noted in the whole cell lysates of breast carcinoma cells and very weak or no bands consistent with alpha 9 subunit were noted in the membrane fraction extracted from the breast carcinoma cells. Significance of alpha 9 beta 1 and alpha v beta 6 integrins expression in breast carcinoma was still unknown on clinicopathological examination. The findings of Western blot analysis may indicate that the transportation system of glycoproteins such as integrins to the cell membrane of carcinoma cells is

  19. Gastric and Colorectal Metastases of Lobural Breast Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    David Buka

    2016-04-01

    Full Text Available Background: Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. Case Report: A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. Conclusions: Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

  20. Impact of weight change during neoadjuvant chemotherapy on pathologic response in triple-negative breast cancer.

    Science.gov (United States)

    Bao, Jean; Borja, Nicholas; Rao, Madhu; Huth, James; Leitch, A Marilyn; Rivers, Aeisha; Wooldridge, Rachel; Rao, Roshni

    2015-04-01

    Triple-negative breast cancer (TNBC) is an uncommon but aggressive subtype of breast cancer. Obesity has been associated with an increased risk of breast cancer and worse prognosis. Some studies suggest that obese patients are less likely to achieve pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) and experience worse overall survival. Ki-67 is a proliferation marker that correlates with tumor aggressiveness. The goal of this study was to examine the impact of weight change during NCT for TNBC on pathologic response and Ki-67 reduction. Retrospective review identified 173 TNBC patients treated between 2004 and 2011. Data were collected on patient demographics, pre- and post-NCT body mass index (BMI), Ki-67, and pCR. Data analysis was performed using the two-tailed Student's t-test, analysis of variance (ANOVA), and Fisher's exact test. Sixty-six patients met final study criteria. Forty-three patients lost weight during chemotherapy and 23 gained weight. Patients in the weight gain group were significantly younger (P = 0.0013). There was no significant difference between the two groups in terms of Ki-67 reduction (P = 0.98) or pCR (P = 0.58). When patients were separated into normal weight (BMI<25 kg/m(2) ), overweight (BMI ≥ 25 and <30 kg/m(2) ), and obese (BMI ≥ 30 kg/m(2) ), there was no significant difference in Ki-67 among those groups either before or after NCT. The degree of obesity did not have a significant impact on Ki-67 reduction. Weight change during NCT does not appear to correlate with Ki-67 change or achieving pCR in TNBC. This may reflect the nature of this subtype of breast cancer that is less responsive to the hormonal effects that adipose tissue exerts on cancer cell proliferation. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Fei Ma

    Full Text Available INTRODUCTION: Triple-negative breast cancer (TNBC is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs. MATERIALS AND METHODS: The surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed. RESULTS: Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014. The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003. Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS in both lymph node positive (LN+ and negative (LN- cases (both P<0.001. Similarly it was also associated with shorter overall survival (OS(P = 0.003 in LN+ cases; P = 0.018 in LN- cases. In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P = 0.008. Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002. However, neither CLDN4 nor CLDN7 expression was associated with survival. CONCLUSION: In TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor

  2. Lymph node status in different molecular subtype of breast cancer: triple negative tumours are more likely lymph node negative.

    Science.gov (United States)

    Liu, Ning; Yang, Zhigang; Liu, Xiaozhen; Niu, Yun

    2017-08-15

    To investigate the association between different molecular subtype (MST) and the axillary lymph nodal (ALN) status. A total of 528 female patients with primary breast cancer were collected. Survival estimates were calculated using the Kaplan-Meier method, univariate and multivariate logistic regression models. Triple negative and Luminal A breast cancers were more frequently node-negative (N0) when compared to Luminal B and Her-2 positive cancers (77.4% and 73.4% vs. 45.3% and 40.0%, respectively; P P = 0.001) and Luminal B (P Triple negative (P = 0.070) and Luminal A subtype (P = 0.660). On the other hand, we detected no prognostic diffreence among different MST in N1 and N3 subgroups (P = 0.569 and P = 0.484, respectively). Multivariate analysis showed that lymph node status (P P P Triple negative breast cancer is not associated more frequently with a higher number of involved nodes. The prognosis nomogram can predict the probability of recurrence patients within 3 or 5 years.

  3. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

    Science.gov (United States)

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-02-28

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  4. High incidence of triple-negative tumors in sub-saharan Africa: a prospective study of breast cancer characteristics and risk factors in Malian women seen in a Bamako university hospital.

    Science.gov (United States)

    Ly, Madani; Antoine, Martine; Dembélé, Abdoul Karim; Levy, Pierre; Rodenas, Anita; Touré, Boubacari Ali; Badiaga, Youssouf; Dembélé, Bakary Kossa; Bagayogo, Djénèba Coulibaly; Diallo, Yacouba Lazare; Koné, Abdramane A; Callard, Patrice; Bernaudin, Jean-François; Diallo, Dapa Aly

    2012-01-01

    Few studies have been conducted on breast cancer in Sub-Saharan Africa and their results have been suspected to be impaired by artefacts. This prospective study was designed to determine tumor and patient characteristics in Mali with control of each methodological step. These data are necessary to define breast cancer treatment guidelines in this country. Clinical and tumor characteristics and known risk factors were obtained in a consecutive series of 114 patients. Each technical step for the determination of tumor characteristics [histology, TNM, grade, estrogen (ER) and progesterone receptors (PR), HER2, and Ki67] was controlled. Patients had a mean age of 46 years. Most tumors were invasive ductal carcinomas (94%), T3-T4 (90%) with positive nodes (91%), grade III (78%), and ER (61%) and PR (72%) negative. HER2 was overexpressed in 18% of cases. The triple-negative subgroup represented 46%, displaying a particularly aggressive pattern (90% grade III; 88% Ki67 >20%). This study demonstrates the high incidence of aggressive triple-negative tumors in Mali. Apart from a higher prevalence of premenopausal women, no significant difference in risk factors was observed between triple-negative tumors and other tumors. The hormonal therapy systematically prescribed therefore needs to be revised in light of this study. Copyright © 2012 S. Karger AG, Basel.

  5. Dynamin 3: a new candidate tumor suppressor gene in hepatocellular carcinoma detected by triple combination array analysis

    Directory of Open Access Journals (Sweden)

    Inokawa Y

    2013-10-01

    Full Text Available Yoshikuni Inokawa,1 Shuji Nomoto,1 Mitsuhiro Hishida,1 Masamichi Hayashi,1 Mitsuro Kanda,1 Yoko Nishikawa,1 Shin Takeda,2 Michitaka Fujiwara,1 Masahiko Koike,1 Hiroyuki Sugimoto,1 Tsutomu Fujii,1 Goro Nakayama,1 Suguru Yamada,1 Chie Tanaka,1 Daisuke Kobayashi,1 Yasuhiro Kodera11Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya Japan; 2Department of Surgery, Nagoya Medical Center, Nagoya, JapanBackground: To identify genes associated with hepatocellular carcinoma (HCC pathogenesis, we developed a triple combination array strategy comprising methylation, gene expression, and single nucleotide polymorphism (SNP array analysis.Methods: Surgical specimens obtained from a 68-year-old female HCC patient were analyzed by triple combination array, and identified Dynamin 3 (DNM3 as a candidate tumor suppressor gene in HCC. Subsequently, samples from 48 HCC patients were evaluated for DNM3 methylation and expression status using methylation specific polymerase chain reaction (PCR; MSP and semi-quantitative reverse transcriptase (RT-PCR, respectively. The relationship between clinicopathological factors and DNM3 methylation status was also investigated.Results: DNM3 was shown to be hypermethylated (methylation value 0.879, range 0–1.0 in cancer tissue compared with adjacent normal tissue (0.213 by methylation array in the 68-year-old female patient. Expression arrays revealed decreased expression of DNM3 in cancerous tissue. SNP arrays revealed that the copy number of chromosome 1q24.3, in which DNM3 resides, was normal. MSP revealed hypermethylation of the DNM3 promoter region in 33 of 48 tumor samples. A trend toward decreased DNM3 expression was observed in patients with DNM3 promoter methylation (P = 0.189. Furthermore, patients with reduced expression of DNM3 in tumor tissues exhibited worse prognosis with decreased disease specific survival compared to patients without decreased expression (P = 0.014.Conclusion: The

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

    Science.gov (United States)

    2012-01-01

    variation. Finally, we confirmed high expression levels of p16 in Triple-negative tumours. Conclusion Factor analysis of multiple IHC biomarkers measured by automated DA is an efficient exploratory tool clarifying complex interdependencies in the breast ductal carcinoma IHC profiles and informative value of single IHC markers. Integrated IHC indices may provide additional risk stratifications for the currently used grading systems and prove to be useful in clinical outcome studies. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1512077125668949 PMID:22424533

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

    Directory of Open Access Journals (Sweden)

    Laurinavicius Arvydas

    2012-03-01

    the major factor of variation. Finally, we confirmed high expression levels of p16 in Triple-negative tumours. Conclusion Factor analysis of multiple IHC biomarkers measured by automated DA is an efficient exploratory tool clarifying complex interdependencies in the breast ductal carcinoma IHC profiles and informative value of single IHC markers. Integrated IHC indices may provide additional risk stratifications for the currently used grading systems and prove to be useful in clinical outcome studies. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1512077125668949

  8. Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple-negative breast cancer, adversely affects survival.

    Science.gov (United States)

    Thike, Aye A; Tan, Puay H; Ikeda, Murasaki; Iqbal, Jabed

    2016-04-01

    Breast cancer 1 (BRCA1) expression is down-regulated in a significant proportion of non-hereditary breast cancers, in the absence of any mutation. This phenomenon is more pronounced in oestrogen (ER)-negative tumours. Recent studies have suggested that inhibitor of DNA binding 4 (ID4), as well as p53, participate in the transcriptional regulation of BRCA1. Immunohistochemical expression of ID4, BRCA1, BRCA2 and p53 in 699 women with triple-negative breast cancer was investigated using tissue microarrays. The prognostic role of these biomarkers was also evaluated. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. Loss of BRCA1 and BRCA2 expression and overexpression of ID4 and p53 was observed in 75%, 90%, 95% and 66% of tumours, respectively. ID4 expression was increased in higher tumour grade (P P P = 0.037) and p53 accumulation (P triple-negative breast cancers (P = 0.041) and basal-like triple-negative breast cancers (P = 0.026). There is frequent ID4 expression and concomitant loss of BRCA proteins in triple-negative breast cancer. We hypothesize that strong ID4 expression could be useful as a prognostic marker in triple-negative breast cancer, predicting early tumour recurrence. © 2015 John Wiley & Sons Ltd.

  9. [10]-Gingerol, a major phenolic constituent of ginger root, induces cell cycle arrest and apoptosis in triple-negative breast cancer cells.

    Science.gov (United States)

    Bernard, Megan M; McConnery, Jason R; Hoskin, David W

    2017-04-01

    The ginger rhizome is rich in bioactive compounds, including [6]-gingerol, [8]-gingerol, and [10]-gingerol; however, to date, most research on the anti-cancer activities of gingerols have focused on [6]-gingerol. In this study, we compared [10]-gingerol with [8]-gingerol and [6]-gingerol in terms of their ability to inhibit the growth of human and mouse mammary carcinoma cells. A colorimetric assay based on the enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide revealed that [10]-gingerol was more potent than [6]-gingerol and at least as potent as [8]-gingerol for the inhibition of triple-negative human (MDA-MB-231, MDA-MB-468) and mouse (4T1, E0771) mammary carcinoma cell growth. Further investigation of [10]-gingerol showed that it suppressed the growth of estrogen receptor-bearing (MCF-7, T47D) and HER2-overexpressing (SKBR3) breast cancer cells. The inhibitory effect of [10]-gingerol on the growth of MDA-MB-231 cells was associated with a reduction in the number of rounds of cell division and evidence of S phase-cell cycle arrest, as well as induction of apoptosis due to mitochondrial outer membrane permeabilization and the release of proapoptotic mitochondrial cytochrome c and SMAC/DIABLO into the cytoplasm. Surprisingly, killing of MDA-MB-231 cells by [10]-gingerol was not affected by a pan-caspase inhibitor (zVAD-fmk) or an anti-oxidant (N-acetylcysteine), suggesting that the cytotoxic effect of [10]-gingerol did not require caspase activation or the accumulation of reactive oxygen species. These findings suggest that further investigation of [10]-gingerol is warranted for its possible use in the treatment of breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Comparison of male breast carcinoma in the Ibos of West-Africa and ...

    African Journals Online (AJOL)

    Comparison of male breast carcinoma in the Ibos of West-Africa and in their ethnologically linked Hebrews of the Middle East. ... Open Access DOWNLOAD FULL TEXT Subscription or ... The literature was searched for such data in Hebrews.

  11. Expression of androgen receptor and prostate-specific antigen in male breast carcinoma

    National Research Council Canada - National Science Library

    Kidwai, Noman; Gong, Yun; Sun, Xiaoping; Deshpande, Charuhas G; Yeldandi, Anjana V; Rao, M Sambasiva; Badve, Sunil

    .... In this study we analyzed the expression of PSA, PSAP and androgen receptor (AR) by immunohistochemistry in 26 cases of male breast carcinomas and correlated these with the expression of other prognostic markers...

  12. The Role of Myoepithelial Maspin in Breast Carcinoma Progression, Diagnosis and Screening

    National Research Council Canada - National Science Library

    Barsky, Sanford

    2002-01-01

    In glandular organs a precancerous stale precedes invasive carcinoma. in the breast this state is recognized as DGIS and consists of an epithelial cell proliferation confined by myoepithelial cells...

  13. Cytodiagnosis of papillary carcinoma of the breast: Report of a case with histological correlation

    Directory of Open Access Journals (Sweden)

    Deepti Aggarwal

    2014-01-01

    Full Text Available Papillary lesions of the breast pose diagnostic challenges on aspiration cytology due to overlapping features of benign and malignant entities. Accurate cytologic diagnosis of papillary breast carcinoma cannot usually be made pre-operatively. We present the case of an adult female who underwent fine-needle aspiration (FNA of a left breast lump. FNA smears were highly cellular showing cohesive clusters, complex papillary fragments and few singly dispersed intact cells. The tumor cells had hyperchromatic nuclei, prominent nucleoli and mild nuclear pleomorphism. A cytologic impression of papillary lesion, possibly malignant (in view of high cellularity, complex papillae and single intact cells was rendered. The lesion proved to be a papillary carcinoma with microscopic foci of stromal invasion on histologic examination. Papillary carcinoma, an uncommon subtype of breast carcinoma, should be considered while evaluating a papillary lesion with complex branching papillae containing delicate fibrovascular cores and singly lying intact atypical cells.

  14. Adenoid cystic carcinoma of the breast: truly uncommon or easily overlooked?

    Science.gov (United States)

    Sheen-Chen, Shyr-Ming; Eng, Hock-Liew; Chen, Wei-Jen; Cheng, Yu-Fan; Ko, Sheung-Fat

    2005-01-01

    Adenoid cystic carcinoma of the breast is an uncommon histologic form of breast cancer, comprising in most series less than 1% of all mammary cancers. Due to the rarity, little information about its presentation on image studies has been noted in the literature. Here we report two additional cases with emphasis on the intriguing image presentations. A 67-year-old woman came to our clinic with the chief complaint of mastodynia. No obvious palpable mass of breast was found on physical examination. Mammography showed a small well-defined nodule in the medial part of the left breast without mammographic evidence of malignancy. Ultrasonography showed a 1.5 cm nodule with well-defined margin and heterogenous echogenicity in the medial part of the left breast. Unusually, a painful sensation was experienced on compression by the probe. The final pathological report was adenoid cystic carcinoma. A 48-year-old woman also came to our clinic with the chief complaint of mastodynia. No obvious palpable mass of breast was found on physical examination. Mammography showed dense mammary tissue with no mammographic evidence of malignancy. Ultrasonography showed two contiguous well-defined nodules with heterogenous echogenicity in the upper, middle part of the left breast. Unusually, a painful sensation was also noted on compression by the probe. Histopathological examination showed typical features of an adenoid cystic carcinoma. Adenoid cystic carcinoma of the breast fails to show the typical appearance of invasive ductal carcinoma on both mammogram and ultrasonography, probably due to its relatively well-defined nature with less surrounding architectural disruption and fibrosis. Hence a "negative" finding or a benign-looking breast lesion on mammography cannot completely exclude the existence of this disease. The presence of a painful breast lesion without obvious inflammatory evidence while compressed is a meaningful clue, which should lead to the suspicion of adenoid cystic

  15. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Energy Technology Data Exchange (ETDEWEB)

    Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

    2014-06-27

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  16. A prognostic gene signature for metastasis-free survival of triple negative breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Unjin Lee

    Full Text Available Although triple negative breast cancers (TNBC are the most aggressive subtype of breast cancer, they currently lack targeted therapies. Because this classification still includes a heterogeneous collection of tumors, new tools to classify TNBCs are urgently required in order to improve our prognostic capability for high risk patients and predict response to therapy. We previously defined a gene expression signature, RKIP Pathway Metastasis Signature (RPMS, based upon a metastasis-suppressive signaling pathway initiated by Raf Kinase Inhibitory Protein (RKIP. We have now generated a new BACH1 Pathway Metastasis gene signature (BPMS that utilizes targets of the metastasis regulator BACH1. Specifically, we substituted experimentally validated target genes to generate a new BACH1 metagene, developed an approach to optimize patient tumor stratification, and reduced the number of signature genes to 30. The BPMS significantly and selectively stratified metastasis-free survival in basal-like and, in particular, TNBC patients. In addition, the BPMS further stratified patients identified as having a good or poor prognosis by other signatures including the Mammaprint® and Oncotype® clinical tests. The BPMS is thus complementary to existing signatures and is a prognostic tool for high risk ER-HER2- patients. We also demonstrate the potential clinical applicability of the BPMS as a single sample predictor. Together, these results reveal the potential of this pathway-based BPMS gene signature to identify high risk TNBC patients that can respond effectively to targeted therapy, and highlight BPMS genes as novel drug targets for therapeutic development.

  17. NY-ESO-1 cancer testis antigen demonstrates high immunogenicity in triple negative breast cancer.

    Science.gov (United States)

    Ademuyiwa, Foluso O; Bshara, Wiam; Attwood, Kristopher; Morrison, Carl; Edge, Stephen B; Karpf, Adam R; James, Smith A; Ambrosone, Christine B; O'Connor, Tracey L; Levine, Ellis G; Miliotto, Anthony; Ritter, Erika; Ritter, Gerd; Gnjatic, Sacha; Odunsi, Kunle

    2012-01-01

    NY-ESO-1 cancer testis (CT) antigen is an attractive candidate for immunotherapy as a result of its high immunogenicity. The aim of this study was to explore the potential for NY-ESO-1 antigen directed immunotherapy in triple negative breast cancer (TNBC) by determining the frequency of expression by immunohistochemistry (IHC) and the degree of inherent immunogenicity to NY-ESO-1. 168 TNBC and 47 ER+/HER2- primary breast cancer specimens were used to determine NY-ESO-1 frequency by IHC. As previous studies have shown that patients with a robust innate humoral immune response to CT antigens are more likely to develop CD8 T-cell responses to NY-ESO-1 peptides, we evaluated the degree to which patients with NY-ESO-1 expression had inherent immunogenicity by measuring antibodies. The relationship between NY-ESO-1 expression and CD8+ T lymphocytes was also examined. The frequency of NY-ESO-1 expression in the TNBC cohort was 16% versus 2% in ER+/HER2- patients. A higher NY-ESO-1 score was associated with a younger age at diagnosis in the TNBC patients with NY-ESO-1 expression (p = 0.026). No differences in OS (p = 0.278) or PFS (p = 0.238) by NY-ESO-1 expression status were detected. Antibody responses to NY-ESO-1 were found in 73% of TNBC patients whose tumors were NY-ESO-1 positive. NY-ESO-1 positive patients had higher CD8 counts than negative patients (p = 0.018). NY-ESO-1 is expressed in a substantial subset of TNBC patients and leads to a high humoral immune response in a large proportion of these individuals. Given these observations, patients with TNBC may benefit from targeted therapies directed against NY-ESO-1.

  18. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Directory of Open Access Journals (Sweden)

    Mirco Pistelli

    2014-06-01

    Full Text Available Background: Triple-negative breast cancers (TNBC are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001 and a lympho-vascular invasion (p = 0.01, but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72 or overall survival (p = 0.93. Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  19. BRCA1/2-negative hereditary triple-negative breast cancers exhibit BRCAness.

    Science.gov (United States)

    Domagala, Pawel; Hybiak, Jolanta; Cybulski, Cezary; Lubinski, Jan

    2017-04-01

    BRCA1/2-associated breast cancers are sensitive to poly(ADPribose) polymerase (PARP) inhibitors and platinum compounds mainly due to their deficiency in DNA repair via homologous recombination (HR). However, approximately only 15% of triple-negative breast cancers (TNBCs) are BRCA1/2-associated. TNBCs that exhibit BRCAness (a phenotype reflecting impaired HR in BRCA1/2-negative tumors) are also regarded sensitive to PARP inhibitors and platinum compounds. Thus, we hypothesized that hereditary BRCA1/2-negative TNBCs may exhibit BRCAness. To find a subset of hereditary BRCA1/2-negative TNBCs among 360 TNBCs, we first identified a group of 41 hereditary TNBCs by analyzing the family histories of the patients. Next, we tested this group for the presence of germline BRCA1/2 mutations, and finally, we compared the expression levels of 120 genes involved in HR and five other major mechanisms of DNA damage repair between BRCA1/2-associated and BRCA1/2-negative subgroups of hereditary TNBCs using real-time PCR arrays. Approximately 73% of the hereditary TNBCs were BRCA1/2-associated and 27% were BRCA1/2-negative. The expression levels of the analyzed genes showed no significant differences between these two subgroups indicating the BRCAness of the BRCA1/2-negative hereditary TNBCs and thereby distinguishing a novel subset of TNBCs as a potential target for PARP inhibitors or platinum-based therapy. The results show the significance of family history in selecting patients with TNBC for therapies directed at incompetent DNA repair (e.g., PARP inhibitors and/or platinum-based therapies) and indicate that a relatively simple strategy for broadening the target group for these modes of treatment is to identify patients with hereditary TNBCs. © 2016 UICC.

  20. Elevated p-CREB-2 (ser 245) expression is potentially associated with carcinogenesis and development of breast carcinoma.

    Science.gov (United States)

    Fan, Chui-Feng; Mao, Xiao-Yun; Wang, En-Hua

    2012-02-01

    CREB-2, also known as ATF-4, belongs to the CREB proteins, a family of transcription factors phosphorylated at serine residues by protein kinase A (PKA). This family is known to stimulate the transcription of genes containing CRE elements. Recently, some studies have demonstrated elevated CREB-2 expression in certain tumor types, including breast carcinoma, compared to their corresponding non-tumor tissues. However, the expression and clinical significance in malignant tumors, including breast carcinoma, of p-CREB-2 (ser 245), a phosphorylated form of the CREB-2 protein at serine 245 site, which is believed to be an active type of this protein, have not been clearly documented. In the present study, we investigated the expression of p-CREB-2 (ser 245) in a group of tumor and non-tumor breast tissues, including normal breast epithelia, hyperplasia, dysplasia, carcinoma in situ and infiltrating carcinoma of the breast using tissue microarray and immunohistochemistry (IHC). p-CREB-2 (ser 245) immunostaining was detected in the nucleus and cytoplasm of these tissues. Compared to normal breast epithelia and breast hyperplasia (total positive rate 13.3%), there was increased expression of p-CREB-2 (ser 245) in dysplasia, carcinoma in situ (total positive rate 35.7%) and infiltrating carcinoma of the breast (total positive rate 60.0%) (pser 245) was found in infiltrating breast carcinoma (total positive rate 60%) compared to normal breast epithelia and all types of non-infiltrating lesions (total positive rate 27.6%) (pser 245) was found to be associated with lymph node metastasis in infiltrating breast carcinoma (pser 245) in breast cancer MCF 7 and MDA-MB-231 cells compared with normal breast epithelial MCF 10A cells. Western blotting revealed elevated expression levels of p-CREB-2 (ser 245) in 17 cases of breast carcinoma compared with corresponding normal breast tissues (pser 245) may potentially contribute to carcinogenesis and cancer development of breast carcinoma.

  1. Multifocal and Multicentric Breast Carcinoma: A Significantly More Aggressive Tumor than Unifocal Breast Cancer.

    Science.gov (United States)

    Lang, Zhiqiang; Wu, Yanqiu; Li, Cuiyan; Li, Xinna; Wang, Xuan; Qu, Guimei

    2017-08-01

    There are still many questions that surround multifocal or multicentric breast carcinoma (MMBC). The aim of this study was to analyze the clinicopathological characteristics of MMBC and provide feasible suggestions for therapy. A total of 156 cases of MMBC in 3,597 invasive ductal breast carcinomas were collected and reviewed. Some factors related with prognosis such as tumor size, lymph node metastasis and others were assessed in each tumor focus, and mismatches among foci were recorded. The majority of MMBC had aggregate dimensions over 2 cm (85.90%). The rate of axillary lymph node metastasis was 56.41% (88/156) compared to unifocal tumors of 33.01% (1,136/3,441). Most cases had higher Ki-67 proliferative indices (91/156). Mismatches in ER status were present in 6 cases, PR in 4 cases, proliferative index (Ki-67) in 9 cases and HER2-positive status in 2 cases. The larger aggregate dimension of tumor, the higher metastatic rate of axillary lymph node and the high Ki-67 proliferative index seen in most cases, suggest that MMBC is biologically more aggressive than unifocal breast cancer. In addition, every focus should be tested owing to the existence of different expressions of immunostaining between foci. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. The role of neoadjuvant chemotherapy of triple-negative breast cancer in St. Petersburg City Clinical Oncological Dispensary

    Directory of Open Access Journals (Sweden)

    A. G. Manikhas

    2016-01-01

    Full Text Available Introduction. Triple-negative breast cancer (BC is very aggressive form of breast malignancies with high levels of dissemination, frequent ecurrence and poor survival rate, as compared to other breast cancer subtypes.Aim of the study – development and introduction of optimized treatment strategy of patients with triple-negative breast cancer into the clinical practice of City Clinical Oncological Dispensary.Materials and methods. The study included 201 patients (21–90 years, mean age 52 years who were treated in the first departmentof St. Petersburg City Clinical Oncological Dispensary from 2005 to 2011. Stage IА–IIIC invasive breast cancer with triple-negative phenotype according to immunohistochemical study of the tumor material was verified in all the patients before beginning of the treatment. Standard chemotherapy by FAC, CMF and taxane-containing regimen was used as neoadjuvant chemotherapy. The degree of therapeutic pathomorphism was evaluated according to Miller-Payne (2003 classification, which was designed taking into account an overall survival rate of patients, depending on the degree of pathologic tumor regression. Results. We performed evaluation of 3-year relapse-free survival, depending on the degree of pathomorphological regression and histological degree of malignancy. There is a clear dependence of the 3-year relapse-free survival on the degree of histological differentiation of the tumor. We noted an inverse correlation between high degree of histological malignancy with a short relapse-free period. The disease progressed in patients who have a high degree of histological malignancy.Conclusion. The highest efficiency was achieved in patients receiving chemotherapy with the addition of taxanes. It is advantageous to include taxane-containing chemotherapy regimens in the treatment of patients with a high degree of histological malignancy.

  3. Axillary lymph node tuberculosis masquerading as inflammatory breast carcinoma in an immune-compromised patient.

    Science.gov (United States)

    Chikkannaiah, Panduranga; Vani, B R; Benachinmardi, Kirtilaxmi; Murthy, V Srinivasa

    2016-02-01

    While tuberculosis is still the leading opportunistic infection among human immunodeficiency virus-seropositive patients, extra-pulmonary tuberculosis is more common than pulmonary tuberculosis, with lymph nodes being a common site. Axillary lymph node pathology such as tuberculosis and lymphoma rarely mimics inflammatory breast carcinoma by producing lymphatic obstruction. We report a case of axillary lymph node tuberculosis in a 40-year-old immune-compromised woman, clinically presenting as inflammatory breast carcinoma. © The Author(s) 2015.

  4. Intracystic Papillary Carcinoma in the Male Breast: A Rare Endpoint of a Wide Spectrum

    Directory of Open Access Journals (Sweden)

    Ketan Vagholkar

    2013-01-01

    Full Text Available Introduction. Fibrocystic disease of the male breast is uncommon. The presence of a spectrum of changes ranging from fibrocystic disease to duct papilloma to papillary carcinoma in the same patient renders the case a rarity and therefore reportable. Case Report. A case of intracystic papillary carcinoma of the male breast is presented. Discussion. The pathological, clinical, diagnostic, and therapeutic options are discussed after reviewing the literature. Conclusion. Modified radical mastectomy with axillary clearance is the safest option for established cases.

  5. Treatment of triple-negative breast cancer with Chinese herbal medicine: A prospective cohort study protocol.

    Science.gov (United States)

    Meng, Hui; Peng, Nan; Yu, Mingwei; Sun, Xu; Ma, Yunfei; Yang, Guowang; Wang, Xiaomin

    2017-11-01

    Triple-negative breast cancer (TNBC) is featured with the biological properties of strong aggressive behaviors, rapid disease progression, high risk of recurrence and metastasis, and low disease free survival. Patients with this tumor are insensitive to the endocrine therapy and target treatment for HER-2; therefore, chemotherapy is often used as routine treatment in clinical. Because of the fact that a considerable number of patients seek for Chinese herbal medicine (CHM) treatment after operation and chemotherapy and (or) radiotherapy, it is thus need to evaluate the correlation between Chinese herbal medicine treatment and prognosis. This is a multicenter, prospective cohort study started in March 2016 in Beijing. A simple of 220 participants diagnosed with TNBC were recruited from nine hospitals and are followed up every 3 to 6 months till March 2020. Detailed information of participants includes personal information, history of cancer, quality of life, symptoms of traditional Chinese medicine and fatigue status is taken face-to-face at baseline. The study has received ethical approval from the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University (No.2016BL-014-01). Articles summarizing the primary results and ancillary analyses will be published in peer-reviewed journals. Chinese Clinical Trial Registry: ChiCTR-OOC-16008246.

  6. Raloxifene reduces triple-negative breast cancer tumor growth and decreases EGFR expression.

    Science.gov (United States)

    Taurin, Sebastien; Allen, Kirstie M; Scandlyn, Marissa J; Rosengren, Rhonda J

    2013-09-01

    The poor prognosis of patients with triple-negative breast cancer (TNBC) and the lack of targeted treatments have raised the need for alternative therapies. Previous studies have suggested an effect of raloxifene, a selective estrogen receptor modulator that is independent of the estrogen receptor (ER). Therefore, we assessed the therapeutic value of raloxifene in TNBC mouse models. Mice received a daily oral treatment with different doses of raloxifene. Tumor progression was monitored weekly; in addition microvessel density, proliferation, migration and invasion, apoptosis and tumorigenicity were analyzed. This study demonstrates that raloxifene (0.85 mg/kg) prevents TNBC tumor growth and induces tumor regression. The treated tumors showed a 54% decreased microvascular density and proliferation and a 7-fold increase in apoptosis. The underlying therapeutic mechanism of raloxifene was associated with a 27-fold decrease in the expression of the epidermal growth factor receptor (EGFR). Moreover, raloxifene promoted the translocation of EGFR into endosomes associated with decreased cell migration, cell invasion and tumorigenicity in vitro. Together, these data showed that raloxifene acts independently of the ER and may be relevant for the treatment as well as control the progression of TNBC.

  7. FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Leandra Fiori Lopes

    2014-01-01

    Full Text Available Triple negative breast cancer (TNBC is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2. FOXP3 (forkhead transcription factor 3 is a marker of regulatory T cells (Tregs, whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548 and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction. Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06 in relation to TNBC susceptibility. Most of the patients (83% showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026. In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

  8. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients.

    Science.gov (United States)

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke; Trapman-Jansen, Anita M A C; Foekens, Renée; Look, Maxime P; Smid, Marcel; van Deurzen, Carolien H M; Span, Paul N; Sweep, Fred C G J; Brask, Julie Benedicte; Timmermans-Wielenga, Vera; Foekens, John A; Martens, John W M; Umar, Arzu

    2016-08-25

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules.

  9. Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer.

    Science.gov (United States)

    Upreti, Meenakshi; Jyoti, Amar; Johnson, Sara E; Swindell, Elden P; Napier, Dana; Sethi, Pallavi; Chan, Ryan; Feddock, Jonathan M; Weiss, Heidi L; O'Halloran, Thomas V; Evers, B Mark

    2016-07-05

    Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The 'rigorous' combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment.

  10. Standard of Care and Promising New Agents for Triple Negative Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Patrizia Mancini

    2014-10-01

    Full Text Available Triple negative breast cancer (TNBC is a cluster of heterogeneous diseases, all of them sharing the lack of expression of estrogen and progesterone receptors and HER2 protein. They are characterized by different biological, molecular and clinical features, including a poor prognosis despite the increased sensitivity to the current cytotoxic therapies. Several studies have identified important molecular features which enable further subdivision of this type of tumor. We are drawing from genomics, transcription and translation analysis at different levels, to improve our knowledge of the molecular alterations along the pathways which are activated during carcinogenesis and tumor progression. How this information should be used for the rational selection of therapy is an ongoing challenge and the subject of numerous research studies in progress. Currently, the vascular endothelial growth factor (VEGF, poly (ADP-ribose polymerase (PARP, HSP90 and Aurora inhibitors are most used as targeting agents in metastatic setting clinical trials. In this paper we will review the current knowledge about the genetic subtypes of TNBC and their different responses to conventional therapeutic strategies, as well as to some new promising molecular target agents, aimed to achieve more tailored therapies.

  11. Standard of Care and Promising New Agents for Triple Negative Metastatic Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mancini, Patrizia, E-mail: patrizia.mancini@uniroma1.it [Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161 (Italy); Angeloni, Antonio [Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161 (Italy); Risi, Emanuela [Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161 (Italy); Orsi, Errico [Department of Surgical Science, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161 (Italy); Mezi, Silvia [Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161 (Italy)

    2014-10-24

    Triple negative breast cancer (TNBC) is a cluster of heterogeneous diseases, all of them sharing the lack of expression of estrogen and progesterone receptors and HER2 protein. They are characterized by different biological, molecular and clinical features, including a poor prognosis despite the increased sensitivity to the current cytotoxic therapies. Several studies have identified important molecular features which enable further subdivision of this type of tumor. We are drawing from genomics, transcription and translation analysis at different levels, to improve our knowledge of the molecular alterations along the pathways which are activated during carcinogenesis and tumor progression. How this information should be used for the rational selection of therapy is an ongoing challenge and the subject of numerous research studies in progress. Currently, the vascular endothelial growth factor (VEGF), poly (ADP-ribose) polymerase (PARP), HSP90 and Aurora inhibitors are most used as targeting agents in metastatic setting clinical trials. In this paper we will review the current knowledge about the genetic subtypes of TNBC and their different responses to conventional therapeutic strategies, as well as to some new promising molecular target agents, aimed to achieve more tailored therapies.

  12. Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy

    Science.gov (United States)

    López-Ozuna, Vanessa M.; Hachim, Ibrahim Y.; Hachim, Mahmood Y.; Lebrun, Jean-Jacques; Ali, Suhad

    2016-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) and its signaling pathway serve as a sub-classifier and predictor of pro-differentiation therapy in TNBC. Using immunohistochemistry and various gene expression in silica analyses we observed that prolactin receptor (PRLR) protein and mRNA levels are down regulated in TNBC cases. In addition, examining correlation of PRLR gene expression with metagenes of TNBC subtypes (580 cases), we found that PRLR gene expression sub-classifies TNBC patients into a new subgroup (TNBC-PRLR) characterized by epithelial-luminal differentiation. Importantly, gene expression of PRL signaling pathway components individually (PRL, PRLR, Jak2 and Stat5a), or as a gene signature is able to predict TNBC patients with significantly better survival outcomes. As PRL hormone is a druggable target we determined the biological role of PRL in TNBC biology. Significantly, restoration/activation of PRL pathway in TNBC cells representative of mesenchymal or TNBC-PRLR subgroups led to induction of epithelial phenotype and suppression of tumorigenesis. Altogether, these results offer potential new modalities for TNBC stratification and development of personalized therapy based on PRL pathway activation. PMID:27480353

  13. Neoadjuvant strategies for triple negative breast cancer: 'state-of-the-art' and future perspectives.

    Science.gov (United States)

    Carbognin, Luisa; Furlanetto, Jenny; Vicentini, Cecilia; Nortilli, Rolando; Pilotto, Sara; Brunelli, Matteo; Pellini, Francesca; Pollini, Giovanni Paolo; Bria, Emilio; Tortora, Giampaolo

    2015-01-01

    Neoadjuvant therapy for triple negative breast cancer (TNBC) has recently generated growing interest given the more aggressive biologic characteristics of such subtype and the lack of approved targeted therapies. Systemic chemotherapy represents the mainstay of treatment for TNBC. Although neoadjuvant chemotherapy has consistently demonstrated higher response rates for TNBC compared to non-TNBC, and the pathological complete response predicts long-term outcome, most patient display residual disease with a higher risk of relapse. In order to improve the outcome of TNBC new chemotherapic combinations, including platinum agents, and different targeted agents such as antiangiogenetics, poly-ADP ribose polymerase (PARP) inhibitors and other small molecule inhibitors are being evaluated in neoadjuvant setting. Currently, the research is ongoing to further characterize TNBC from a phenotypical and molecular perspective, in order to identify potential new target agents and to individualize the treatment. In this regard, the neoadjuvant setting may represent the best potential scenario to assess the activity and the sensitivity of novel agents.

  14. Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer?

    Science.gov (United States)

    Synnott, N C; Murray, A; McGowan, P M; Kiely, M; Kiely, P A; O'Donovan, N; O'Connor, D P; Gallagher, W M; Crown, J; Duffy, M J

    2017-01-01

    The identification and validation of a targeted therapy for patients with triple-negative breast cancer (TNBC) is currently one of the most urgent needs in breast cancer therapeutics. One of the key reasons for the failure to develop a new therapy for this subgroup of breast cancer patients has been the difficulty in identifying a highly prevalent, targetable molecular alteration in these tumors. Recently however, the p53 gene was found to be mutated in approximately 80% of basal/TNBC, raising the possibility that targeting the mutant p53 protein product might be a new approach for the treatment of this form of breast cancer. In this study, we investigated the anti-cancer activity of PRIMA-1 and PRIMA-1MET (APR-246), two compounds which were previously reported to reactivate mutant p53 and convert it to a form with wild-type (WT) properties. Using a panel of 18 breast cancer cell lines and 2 immortalized breast cell lines, inhibition of proliferation by PRIMA-1 and PRIMA-1MET was found to be cell-line dependent, but independent of cell line molecular subtype. Although response was independent of molecular subtype, p53 mutated cell lines were significantly more sensitive to PRIMA-1MET than p53 WT cells (p = 0.029). Furthermore, response (measured as IC50 value) correlated significantly with p53 protein level as measured by ELISA (p = 0.0089, r=-0.57, n = 19). In addition to inhibiting cell proliferation, PRIMA-1MET induced apoptosis and inhibited migration in a p53 mutant-dependent manner. Based on our data, we conclude that targeting mutant p53 with PRIMA-1MET is a potential new approach for treating p53-mutated breast cancer, including the subgroup with triple-negative (TN) disease. © 2016 UICC.

  15. Sensitivity of imaging for multifocal-multicentric breast carcinoma

    Directory of Open Access Journals (Sweden)

    Viale Giuseppe

    2008-09-01

    Full Text Available Abstract Background This retrospective study aims to determine: 1 the sensitivity of preoperative mammography (Mx and ultrasound (US, and re-reviewed Mx to detect multifocal multicentric breast carcinoma (MMBC, defined by pathology on surgical specimens, and 2 to analyze the characteristics of both detected and undetected foci on Mx and US. Methods Three experienced breast radiologists re-reviewed, independently, digital mammography of 97 women with MMBC pathologically diagnosed on surgical specimens. The radiologists were informed of all neoplastic foci, and blinded to the original mammograms and US reports. With regards to Mx,