Abstract
We studied androgen receptor (AR) gene expression in primary breast cancer (BC) to determine associations with clinical characteristics and outcomes in the I-SPY 1 study. AR was evaluated in I-SPY 1 (n = 149) using expression microarrays. Associations of AR with clinical and tumor features were determined using the Wilcoxon rank sum test (two-level factors) or the Kruskal-Wallis test (multi-level factors). We identified an optimal AR cut-point to maximize recurrence-free survival (RFS) differences between AR biomarker stratified groups, and assessed the association between the AR stratified groups and RFS using the Cox proportional hazard model. Pearson correlations between AR and selected genes were determined in I-SPY 1, METABRIC (n = 1992), and TCGA (n = 817). AR was lower in triple negative BC vs. hormone receptor positive (HR+)/HER2- and HER2+ disease (p < 0.00001), and lower in basal-like BC (p < 0.00001). AR was higher in grade I/II vs. III tumors (p < 0.00001), in patients >age 50 (p = 0.05), and in node negative disease (p = 0.006). Higher AR was associated with better RFS (p = 0.0007), which remained significant after receptor subtype adjustment (p = 0.01). AR correlated with expression of luminal, HER2, and steroid hormone genes. AR expression was related to clinicopathologic features, intrinsic subtype, and correlated with improved outcome.