Identifying High-Risk Triple-Negative Breast Cancer Patients by Molecular Subtyping

Introduction: Triple-negative breast cancer (TNBC) is considered the most aggressive type of breast cancer (BC) with limited options for therapy. TNBC is a heterogeneous disease and tumors have been classified into TNBC subtypes using gene expression profiling to distinguish basal-like 1, basal-like 2, immunomodulatory, mesenchymal, mesenchymal stem-like, luminal androgen receptor (LAR), and one nonclassifiable group (called unstable). Objectives: The aim of this study was to verify the clinical relevance of molecular subtyping of TNBCs to improve the individual indication of systemic therapy. Patients and Methods: Molecular subtyping was performed in 124 (82%) of 152 TNBC tumors that were obtained from a prospective, multicenter cohort including 1,270 histopathologically confirmed invasive, nonmetastatic BCs (NCT 01592825). Treatment was guideline-based. TNBC subtypes were correlated with recurrence-free interval (RFI) and overall survival (OS) after 5 years of observation. Results: Using PAM50 analysis, 87% of the tumors were typed as basal with an inferior clinical outcome compared to patients with nonbasal tumors. Using the TNBCtype-6 classifier, we identified 23 (15%) of TNBCs as LAR subtype. After standard adjuvant or neoadjuvant chemotherapy, patients with LAR subtype showed the most events for 5-year RFI (66.7 vs. 80.6%) and the poorest probability of 5-year OS (60.0 vs. 84.4%) compared to patients with non-LAR disease (RFI: adjusted hazard ratio [aHR] = 1.87, 95% confidence interval [CI] 0.69–5.05, p = 0.211; OS: aHR = 2.74, 95% CI 1.06–7.10, p = 0.037). Conclusion: Molecular analysis and subtyping of TNBC may be relevant to identify patients with LAR subtype. These cancers seem to be less sensitive to conventional chemotherapy, and new treatment options, including androgen receptor-blocking agents and immune checkpoint inhibitors, have to be explored.

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Risk of SARS-CoV-2 infection and disease in metastatic triple-negative breast cancer patients treated with immune checkpoint inhibitors

Immunotherapy ◽

10.2217/imt-2020-0142 ◽

2020 ◽

Cited By ~ 1

Author(s):

Patrizia Vici ◽

Laura Pizzuti ◽

Eriseld Krasniqi ◽

Andrea Botticelli ◽

Gennaro Ciliberto ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Triple Negative ◽

Checkpoint Inhibitors ◽

Breast Cancer Patients

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Androgen receptor expression as a prognostic and predictive marker in triple-negative breast cancer patients

Alexandria Journal of Medicine ◽

10.1016/j.ajme.2015.06.002 ◽

2016 ◽

Vol 52 (2) ◽

pp. 131-140 ◽

Cited By ~ 4

Author(s):

Fatma Zakaria ◽

Nehal El-Mashad ◽

Dareen Mohamed

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Predictive Marker ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Breast Cancer Patients

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Should Tumor Infiltrating Lymphocyes, Androgen Receptor, and FOXA1 expression predict Clinical Outcome in Triple Negative Breast Cancer Patients?

10.20944/preprints201908.0109.v1 ◽

2019 ◽

Author(s):

Anita Mangia ◽

Concetta Saponaro ◽

Alessandro Vagheggini ◽

Giuseppina Opinto ◽

Matteo Centonze ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Clinical Outcome ◽

Triple Negative Breast Cancer ◽

Poor Prognosis ◽

Triple Negative ◽

Disease Free Survival ◽

Cancer Type ◽

Breast Cancer Patients ◽

Foxa1 Expression

Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. TILs has a strong prognostic role in triple negative breast cancer (TNBC). Little is known about his interaction with Androgen receptor (AR) and Forkhead box A1 (FOXA1). We analyzed the relationships between TIL levels, AR and FOXA1 expression and their clinical significance in TNBC patients. Further, we investigated their interaction with other biomarkers like programmed cell death ligand-1 (PD-L1), Breast Cancer Type 1 susceptibility protein (BRCA1), Poly [ADP-Ribose] Polymerase 1 (PARP1) and Na+/H+ Exchanger Regulatory Factor 1 (NHERF1). The expression of the proteins was evaluated by immunohistochemistry in 124 TNBC samples. TILs were performed adhering to International TILs Working Group 2014 criteria. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis. Multivariate analysis identified TILs as independent prognostic factor of disease free survival (DFS) (p=0.045). A Kaplan-Meyer analysis revealed that the patients with high TILs had a better DFS compared to patients with low TILs (p=0.037), and the phenotypes TILs-/AR+ and TILs-/FOXA1- had a worse DFS (p=0.032, p=0.001 respectively). AR was associated with FOXA1 expression (p=0.007), and the tumors FOXA1+ presented low levels of TILs (p=0.028). A poor DFS was observed for AR+/FOXA1+ tumors compared to other TNBCs (p=0.0117). Low TILs score was associated with poor patients’ survival, and TILs level in combination with AR or FOXA1 expression affected patient’s clinical outcome. In addition, AR+/FOXA1+ phenotype identified a specific subgroup of TNBC patients with poor prognosis. These data may suggest new ways of therapeutic intervention to support current treatments.

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Androgen Receptor Expression in Triple-Negative Breast Cancer

Archives of Breast Cancer ◽

10.32768/abc.20196290-94 ◽

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.

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