Androgen Receptor Levels and Association with PIK3CA Mutations and Prognosis in Breast Cancer

Purpose: To examine the androgen receptor (AR) levels in breast cancer and to assess the impact of AIR expression on patient outcomes. Experimental Design: Reverse-phase protein arrays were used to measure AR levels and a mass spectroscopy-based approach was used to detect PIK3CA mutations. Means and SDs were generated for AR levels. Linear regression models were used to determine if AIR levels differed by tumor subtype and PIK3CA mutation status. Two-sample t tests were used to identify pair-wise differences. Survival probabilities were estimated with the use of the Kaplan-Meier product and log-rank test. Results: The median age was 59 years (23-89 years). Significant differences in AR levels existed among different breast tumor subtypes (highest in estrogen receptor-positive and/or progesterone receptor-positive tumors) as well as by PIK3CA mutation status (P<0.0001 for both). AR levels were significantly higher in breast tumors with kinase domain PIK3CA mutations versus tumors that are wild type or with PIK3CA helical Mutations (P=0.017 and P<0.0001, respectively). In 347 patients, dichotomized AIR level by the median was a significant prognostic factor of recurrence-free survival (P=0.0002) and overall survival (P=0.004). High AR levels were associated with a significantly improved recurrence-free survival in 207 patients with early-stage estrogen/progesterone receptor-positive tumors after adjuvant hormonal therapy. A trend (P=0.07) was found toward higher AIR expression in PIK3CA mutant versus PIK3CA wild-type triple-negative breast tumors. Conclusions: AR levels may represent a prognostic marker in breast cancers and may provide a valuable tool for selecting treatment. There was an association of PIK3CA mutation (kinase domain) with increased AR levels.