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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted.

Androgen Receptor in Breast Cancer: From Bench to Bedside

“…A multi-institutional study of 1,407 TNBC patients from six international cohorts found that AR status presents population-specific patterns related to OS. AR positivity is a biomarker of favorable prognosis in the Nigerian and US cohorts, whereas it correlated with poor prognosis in the Indian, Norway, and Ireland cohorts, while being neutral in the UK cohort ( 55 ).…”

“…To some extent, the prognostic discrepancy mentioned above may be owing to differences in sample sizes, the methodology of detection, the antibody used to test AR, the cut-off values used to define AR positivity, the ethnic composition of cohorts, adjuvant treatments, and follow-up time of studies ( 55 , 64 , 65 ).…”

The Clinical Importance of Androgen Receptor Status in Response to Neoadjuvant Chemotherapy in Turkish Patients with Local and Locally Advanced Breast Cancer

“…The AR positivity rate and prognostic impact in breast cancer vary in different populations. For example, in a multi-institutional study, AR-positive status was found to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norwegian, Irish, and Indian cohorts, and a neutral marker in the UK cohort [19]. In a trial that included 263 Italian patients who received standard treatment (NACT/adjuvant chemotherapy and surgery) for stage I-III triple-negative breast cancer (TNBC), it was found that 29.7% of patients were AR positive and that AR positivity was associated with worse outcomes, especially distant DFS [20].…”

Glycogen-rich Clear Cell Carcinoma of the Breast: A Comprehensive Review

“…[47][48][49] Most of them revealed the predominance of AR expression among ER-positive (luminal) breast cancers, although up to 20% of TNBC may also overexpress AR. [50][51][52][53] Several clinical trials with anti-AR treatment modalities in AR-positive breast cancers have shown potential therapeutic effects. 48,[54][55][56][57] However, ARv7 has recently emerged as an important predictive biomarker that is frequently expressed in advanced prostate carcinomas resistant to anti-AR treatment modalities.…”