Clinicopathologic characteristics of triple-negative breast cancer and relationship to basal markers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11519-e11519
Author(s):  
Dimitrios Tryfonopoulos ◽  
Georgios Oikonomopoulos ◽  
Stamatina Demiri ◽  
Lazaros Lekakis ◽  
Nikolaos Fragkiskos Pistamaltzian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Stage Iv ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Clinicopathologic Characteristics ◽  
Ki 67 ◽  
Immunohistochemical Markers ◽  
Gene Expression Studies

e11519 Background: Triple negative breast cancers are immunohistochemical surrogates of basal-like breast cancers. There is no complete overlap between triple negative and basal-like tumors and as gene expression studies evolve, further subclassification bearing clinical relevance is underway. Our purpose was to correlate clinicopathologic characteristics of triple negative breast cancer tumors with expression of basal markers in an effort to define immunohistochemically subgroups of this heterogenous disease Methods: Data were retrieved and analysed using our electronic databank. Patient samples were reviewed by an expert breast cancer pathologist and stained additionally for EGFR and CK 5/6 antibodies. Results: Sixty-five women with triple negative breast cancer were identified. Mean age was 58.3±12.9 years. Most tumors (86%) were of ductal histology, 53% grade 3, 48% having high Ki-67 index (>14%). 10% of patients presented with Stage IV, 25% with Stage III, 38% with stage II and 27% with stage I disease. 63% of patients were postmenopausal. EGFR staining was present in 43% of tumor samples, whereas CK 5/6 in 38.5%. Both EGFR and CK 5/6 expression was found in 18.5%, whereas 37% of tumors expressed neither EGFR or CK 5/6. No difference was observed between tumors expressing any of these 2 basal markers as compared to EGFR and CK 5/6 negative tumors in terms of Ki-67 index, grade, tumor size and nodal involvement. Lymphovascular invasion and non-ductal histology tended to occur more frequently (p=ns) in non-basal tumors. Additionally, patients with expression of any of the basal markers tended to be more obese than the non-basal triple negative breast cancer patients (p=ns). Conclusions: Further immunohistochemical markers apart from EGFR and CK 5/6 are needed in order to further define clinically meaningful subgroups of triple negative breast cancer.

Clinical characteristics and chemotherapy options of triple-negative breast cancer: Role of classical CMF regimen.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1053-1053
Author(s):  
Min Hee Hur ◽  
Tae Ho Kang ◽  
Ra Joo Im ◽  
Se Won Kim ◽  
Chan Seok Yoon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Positive Lymph Node ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Clinicopathologic Characteristics ◽  
Large Tumor ◽  
Survival Difference ◽  
High Stage

1053 Background: Triple-negative breast cancer is a high risk breast cancer that lacks the benefit of specific targeted therapy. We investigated the clinicopathologic characteristics between triple-negative breast cancers (TNBC) and non-TNBC. And we also analyzed the effect of chemotherapy options such as classical CMF regimen, anthracycline-based, or taxane-based chemotherapy. Methods: A total of 826 invasive breast cancer patients were evaluated from March 2003 to December 2008. We investigated them retrospectively, who had the median follow-up for 88 months. We examined the differences between TNBC compared with non-TNBC in relation to the clinicopathologic parameters, chemotherapy regimen, overall survival (OS). Results: 156 (18.9%) cases among 826 patients were triple negative breast cancers. There were significantly positive associations with younger age (below 35 years), large tumor (>2cm), high stage, poorly differentiated nuclear grade, poorly histologic grade in TNBC. Positive lymph node, lymphovascular invasion were not significantly different between TNBC and non- TNBC. A total of 677 patients were treated with chemotherapy. In TNBC patients, 142 (93.4%) patients were treated with chemotherapy more than in 535 (61.4%) of non- TNBC patients. The chemotherapy in TNBC patients was composed of classical CMF (47.9%), anthracycline-based regimen (25.4%), taxane-based regimen (26.8%). 19 cases (12%) of TNBC experienced locoregional or systemic metastases. 48 (7.2%) patients of non- TNBC did local or systemic metastases. Patients with TNBC had worse 5-year OS than with non-TNT (95.7% vs 98.6%, p=0.01). Interestingly, patients treated with CMF regimen were better 5-year OS than with anthracycline-based, or taxane-based regimen in TNBC (100% vs 96.9% vs 89.2%, p=0.001). There was no survival difference among chemotherapy regimens in non-TNBC patients. Conclusions: Patients with TNBC have poor prognosis compared with non-TNBC. Classical CMF regimen for TNBC patients may be more effective than anthracycline-based or taxane-based regimens.

scholarly journals Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Patient Derived Xenograft

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

scholarly journals The expression and clinical significance of GADD45A in breast cancer patients

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5344 ◽  
Author(s):  
Junnan Wang ◽  
Yiran Wang ◽  
Fei Long ◽  
Fengshang Yan ◽  
Ning Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Expression Levels ◽  
Cancer Tissues

BackgroundGrowth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) was previously found to be associated with risk of several kinds of human tumors. Here, we studied the expression and clinical significance of GADD45A in breast cancer.MethodsWe performed an immunohistochemical study of GADD45A protein from 419 breast cancer tissues and 116 adjacent non-neoplastic tissues.ResultsSignificantly high GADD45A expression were observed in breast cancer tissues compared with adjacent non-neoplastic tissues (P < 0.001) and were independently correlative with estrogen receptor negative (P = 0.028) and high Ki-67 index (P < 0.001). Kaplan–Meier survival analysis revealed that patients with high GADD45A expression levels had a worse long-term prognosis in triple negative breast cancer (P = 0.041), but it was not an independent prognostic factor in multivariate analysis (P = 0.058).ConclusionsGADD45A expression levels are significantly correlative with estrogen receptor status and Ki-67 index in human breast cancer. Patients with triple negative breast cancer might be stratified into high risk and low risk groups based on the GADD45A expression levels.

Prognostic value of Ki-67 labeling index according to age in patients with non-metastasic triple-negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12118-e12118
Author(s):  
Victor Zenzola ◽  
María Antonia Cabezas-Quintario ◽  
Andrea Correa ◽  
Irene Moreno ◽  
Manuel Pedregal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Roc Curve ◽  
Prognostic Value ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Time Dependent ◽  
Clinicopathologic Characteristics ◽  
Ki 67 ◽  
Poor Prognostic Factor

e12118 Background: The prognostic value of Ki67 in triple negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determined the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy. Methods: 201 patients treated for primary TNBC from 1999 to 2014 were identified from the breast surgery database. Clinicopathologic characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow up. A Ki-67 cut-off point was set up to maximize sensitivity and specificity. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis. Results: There was a non-significant Ki-67 cut off value to predict OS and DFS at 3 and 5 years neither in the whole serie (201) nor in the adjuvant group (125), and only a slightly better threshold for DFS in the neoadjuvant one (N = 46) at 5 years (AUC = 0.697). According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60%. In the multivariate analysis (COX proportional hazards regression), high Ki-67 ( > 60%), was a poor prognostic factor for DFS in patients > 40 yo. Among the patients < 40 yo, high Ki-67 was a better prognosis factor. Conclusions: Our data suggest that a threshold of Ki-67 of 60% could provide a usefull tool to define patients with significantly different outcome in TNBC.

scholarly journals Androgen Receptor Expression in Triple-Negative Breast Cancer

2019 ◽  
pp. 90-94
Author(s):  
Samane Jam ◽  
Alireza Abdollahi ◽  
Sanaz Zand ◽  
Zahra Khazaeipour ◽  
Ramesh Omranipour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Lymphovascular Invasion ◽  
Triple Negative ◽  
Tumor Grade ◽  
Receptor Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Cross Sectional

Background: Triple-negative breast cancer (TNBC) accounts for 15 to 20% of all breast cancers. These patients do not benefit from hormone therapy and other targeted treatments of breast cancer. Recently, researchers proposed the use of androgen receptor (AR)-targeted therapies in this subset of patients. The rate of AR expression in TNBC patients varies from 0 to 53%. AR positivity is associated with a better outcome for breast cancer patients. The purpose of this study was to evaluate AR status in TNBC patients and its association with other demographic and pathologic features.Methods: This cross-sectional study was conducted in the Cancer Institute of Iran, affiliated with Tehran University of Medical Sciences, in 2015. Archived formalin-fixed, paraffin-embedded breast tumor blocks were evaluated to determine the AR status of the tumors. Demographic and pathologic characteristics of the patients were retrieved from the department of pathology database. Data were analyzed with SPSS 18.0.Results: Seventy-seven TNBC patients with the mean age of 45.3 ± 11.5 were assessed. Twenty-six patients (34%) showed AR expression, and 51 patients (56%) did not have AR expression. There was no significant correlation between AR status and age, tumor size, histopathologic type of tumor, or lymph node involvement. However, AR positivity had a statistically significant association with a lower tumor grade and lymphovascular invasion (P = 0.029 and P = 0.01, respectively).Conclusion: TNBC patients with AR expression tend to have lower tumor grades and higher rates of lymphovascular invasion.

scholarly journals Overexpression of miRNA-3613-3p Enhances the Sensitivity of Triple Negative Breast Cancer to CDK4/6 Inhibitor Palbociclib

2020 ◽  
Vol 10 ◽  
Author(s):  
Yuanhang Yu ◽  
Han Liao ◽  
Rong Xie ◽  
Yue Zhang ◽  
Renjing Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progesterone Receptors ◽  
Predictive Biomarker ◽  
Inhibitory Effect ◽  
Breast Cancer Patients ◽  
Ki 67

Triple negative breast cancer (TNBC) is characterized by lack of expression of the estrogen and progesterone receptors and HER2, which are common therapeutic targets. CDK4/6 inhibitor Palbociclib has been approved as an anti-cancer agent for breast cancer. However, identifying biomarkers that predict the response to Palbociclib has always been a challenge for molecular targeted therapy. In this study, we identify microRNA as a hallmark in TNBC patients and explore if miR-3613-3p might serve as a tumor suppressor biomarker for triple negative breast cancer patients and if overexpression of miR-3613-3p could enhance the sensitivity of TNBC cells to Palbociclib. We show that the expression of miR3613-3p was down-regulated in TNBC tumors and cells, and the overexpression of miR-3613-3p in patients’ tumor tissues was clinically and pathologically correlated with favorable prognosis, such as smaller tumor size and the lower Ki-67. In vitro, overexpression of miR-3613-3p inhibited cell proliferation, induced G1 cell-cycle arrest, and enhanced the sensitivity of TNBC cells to Palbociclib treatment. In vivo study revealed that overexpression of miR-3613-3p inhibited TNBC tumorigenesis and exerted a significant inhibitory effect of Palbociclib on MDA-MB-231 cells. Mechanically, SMAD2 and EZH2 were found to be two direct targets of miR-3613-3p and mediate the proliferation of TNBC cells and the sensitivity of the cells to Palbociclib through inducing cellular senescence. Our findings suggested that miR-3613-3p acts as a cancer-suppressor miRNA in TNBC. Moreover, our study showed that miR-3613-3p might be used as a predictive biomarker for the response of TNBC to Palbociclib.

scholarly journals Disease-free Probability and Triple-Negative Breast Cancer

2012 ◽  
Vol 35 (1) ◽  
pp. 5-13
Author(s):  
Prakasit Chirappapha ◽  
Thongchai Sukarayothin ◽  
Yodying Wasuthit ◽  
Ronnarat Suvikapalornkul ◽  
Panuwat Lertsithichai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Triple Negative Breast Cancer ◽  
Distant Metastasis ◽  
Triple Negative ◽  
Free Probability ◽  
Growth Factor Receptor ◽  
Tumor Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients

Objective: To compare the probabilities of local recurrence and distant metastasis between women with triple-negative and non- triple negative breast cancers. Methods: Medical and pathological records of breast cancer patients treated between the years 2002 and 2006 were reviewed. Results: There were 256 patients with complete data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression determinations. There were 54 patients (21%) with triple-negative (ER-, PR-, HER2 -) cancers. Triple-negative patients were more likely to have larger tumors with higher histologic grade. The median fallow-up time was 4 years. The probabilities of local and distant recurrence were similar between the two groups of patients. Only two factors were independently and significantly associated with overall recurrence: tumor stage and tumor size. Conclusion: Triple-negative breast cancer did not have a higher risk for both local recurrence and distant metastasis when compared with non-triple negative cancer.

scholarly journals Androgen receptor and FOXA1 coexpression define a “luminal-AR” subtype of feline mammary carcinomas, spontaneous models of breast cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Elie Dagher ◽  
Violette Royer ◽  
Paul Buchet ◽  
Jérôme Abadie ◽  
Delphine Loussouarn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancers ◽  
Cancer Specific Survival ◽  
Ki 67 ◽  
Mammary Carcinomas ◽  
Definition Of

Abstract Background Invasive mammary carcinomas that spontaneously develop in female cats are associated with high mortality, and resemble the most aggressive human breast cancers, especially triple-negative breast cancer (TNBC). Transcriptome studies showed that TNBCs are a heterogeneous group that includes a potentially hormone-dependent subtype named luminal-AR. Some authors proposed an immunohistochemical definition of the luminal-AR subtype, which is not only positive for Androgen Receptor (AR), but also either positive for the transcription factor Forkhead box A1 (FOXA1), or negative for basal markers. The objectives of this study were to describe AR and FOXA1 expressions in feline mammary carcinomas (FMCs), their prognostic value, and if their coexpression could define a “luminal-AR” subtype of triple-negative mammary carcinomas in cats. Methods In a previously described retrospective cohort of 180 female cats with FMCs, with a 2-year follow-up post-mastectomy, we assessed AR, FOXA1, ER, PR, Ki-67, HER2, and CK14 expressions by automated immunohistochemistry. Results Of the 180 FMCs, 57 (32%) were luminal; i.e., ER and/or PR positive, and 123 (68%) were triple-negative (ER–, PR– and HER2–) FMCs. AR overexpression (found in 33 cases/180, 18%) and FOXA1 index ≥1% (64/180, 36%) were associated with a longer disease-free interval, overall survival, and cancer-specific survival in cats with FMC. Analysis of AR, FOXA1 and CK14 coexpression in triple-negative FMCs showed that AR+ triple-negative FMCs were heterogeneous: there existed an AR+ FOXA1+ CK14– subgroup (n = 7) associated with a better cancer-specific survival by multivariate survival analysis (HR = 0.26, 95% CI: 0.07–0.89, p = 0.03) compared to AR+ FOXA1–CK14+ triple-negative FMCs (n = 46) (HR = 1.00), independently of the pathologic tumor size and pathologic nodal stage. The non-basal-like subtype of triple-negative FMCs that coexpresses AR and FOXA1 (the AR+ FOXA1+ CK14– subgroup) could represent the equivalent of the luminal-AR subgroup of human triple-negative breast cancer. Conclusions We identified an AR+ FOXA1+ CK14– subgroup of triple-negative FMCs that might correspond to the luminal-AR subgroup of human triple-negative breast cancers. Cats with FMC may be interesting spontaneous animal models to investigate new strategies targeting the androgen receptor, especially in the aggressive subtype of AR+ basal-like triple-negative mammary carcinomas with loss of FOXA1 expression (the AR+ FOXA1–CK14+ subgroup).

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