Androgen Receptor Expression in Breast Cancer with Special Relation to Triple-Negative Molecular Phenotype and its Response to Anterior Chemotherapy

Abstract

Background: Triple negative breast cancers (TNBC) are a group of tumors with negative expression of estrogen receptor (ER), progesterone receptor (PR);and the human epidermal growth factor receptor 2 (HER2). These are said to arise from basal layer and represent a heterogeneous group of neoplasms that are diverse in behavior, outcome and response to therapy. The only systemic therapy currently available is chemotherapy but prognosis remains poor. There has been renewed interest in evaluating the expression of androgen receptor (AR) particularly among the TNBC imparting a better prognosis. In the present study an attempt has been made to evaluate AR expression in TNBC and response to taxane and/or anthracycline-based standard chemotherapy regimen. Material(s) and Method(s): Between May 2011 and Sept 2012, 116 breast cancer patients were enrolled. Tissue sections were immunostained for ER, PR, Her2 Neu and AR. n = 30 patients with TNBC were sub-grouped.n = 24 patients were subjected to neoadjuvant taxane and/or anthracycline-based chemotherapy according to standard treatment guidelines. Clinical response was evaluated using revised RECIST guidelines (version 1.1). Result(s): In particular, AR expression was commonly observed in luminal A 21/27 (77.8%) and B 19/30 (63.3%) cancers, but was less frequently seen in HER2 cancers 16/29 (55.1%). Despite being defined by the absence of ER and PR expression and being considered hormonally unresponsive, 9/30 (30%) of TNBC expressed androgen receptor.24/30 (80%) TNBCs were given NAC, 7/24 (29.1%) were AR positive. TNBC AR + ve showed better response to NAC as 5/7 (71%) were partial or complete responders compared with 3/17 (17.6%) TNBC AR-ve. Remaining 14/17 (82.6%) TNBC AR-ve showed stable or progressive disease. Conclusion(s): Expression of AR is seen in approximately one-third of TNBCs, with positively stained TNBCs showin to have better response to chemotherapy, providing further evidence that TNBCs represent a heterogeneous group. As AR is confirmed as biologically relevant in TNBC, it is possible that hormonal manipulations targeting it could be useful in treatment, but a large sample size is needed to confirm this conclusion.