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Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

ABSTRACT: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR's prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients' prognosis. We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n = 420), UK (n = 239), Norway (n = 104), Ireland (n = 222), Nigeria (n = 180), and India (n = 242); total n = 1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. AR status shows population-specific patterns of association with patients' overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted.

SUBMITTER: Bhattarai S

PROVIDER: S-EPMC6678933 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

Bhattarai Shristi S Klimov Sergey S Mittal Karuna K Krishnamurti Uma U Li Xiaoxian Bill XB Oprea-Ilies Gabriela G Wetherilt Ceyda Sonmez CS Riaz Ansa A Aleskandarany Mohammed A MA Green Andrew R AR Ellis Ian O IO Cantuaria Guilherme G Gupta Meenakshi M Manne Upender U Agboola Johnson J Baskovich Brett B Janssen Emiel A M EAM Callagy Grace G Walsh Elaine M EM Mehta Anurag A Dogra Atika A Shet Tanuja T Gajaria Pooja P Traina Tiffany T Nggada Haruna A HA Omonisi Abidemi A Ahmed Saad A SA Rakha Emad A EA Rida Padmashree P Aneja Ritu R

Cancers 20190717 7

<h4>Background</h4>The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR's prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients' prognosis.<h4>Methods</h4>We evaluated the prognostic value ...[more]

PMID: 31319547

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Project description:IntroductionOverexpression of the androgen receptor (AR) characterizes a distinct molecular subset of triple negative breast carcinomas (TNBC). The role of AR as a prognostic/predictive biomarker in TNBC is controversial, but increasing evidence suggests that this subset may respond to therapeutic agents targeting AR. Evaluation of AR has not been standardized, and criteria for selection of patients for antiandrogen therapy remain controversial. In this study we determine the appropriate threshold of AR immunoreactivity to define AR positive (AR+) TNBC, describe the clinicopathologic features of AR+ TNBC, and discuss the utility of AR positivity as a prognostic and predictive marker in TNBC.Materials and methods135 invasive TNBC processed in accordance with ASCO/CAP guidelines, were immunostained for AR. Clinicopathologic features of AR+ TNBC were analyzed and compared to AR negative (AR-) TNBC. Patients' age, tumor size, tumor grade, lymph node status, proliferation rate, immunopositivity for EGFR, CK5/6, Ki-67, and disease free survival (DFS) were evaluated statistically.ResultsA 1% cutpoint was confirmed as the appropriate threshold for AR positivity. Using this cutpoint 41% of 135 TNBC were AR+. AR+ TNBC occurred in older women, were larger, had lower mean proliferation rate and increased incidence of axillary metastasis than AR- TNBC. 76% of TNBC with apocrine morphology were AR+. A subset of AR+TNBC expressed basal markers (EGFR and CK5/6). A prognostic model was created.SummaryAR identifies a heterogeneous group of TNBC. Additional evaluation of EGFR expression allowed us to stratify TNBCs into 3 risk groups with significant differences in DFS and therapeutic implications: low-risk (AR+ EGFR-) which represents the LAR molecular subtype with the best prognosis and may benefit the most from anti-androgen therapies; high-risk (AR- EGFR+) which represents the basal molecular subtype with the worst prognosis and may benefit the most from chemotherapy regimens; intermediate-risk (AR+EGFR+ and AR-EGFR-) TNBC with an intermediate prognosis. Prospective trials are required to further validate this prognostic and predictive grouping.

Dataset Information

Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

Publications

Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

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