Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status

Abstract

In this study we sought to correlate androgen receptor (AR) expression with tumor progression and disease-free survival (DFS) in breast cancer patients. We investigated AR expression in 450 breast cancer patients. We found that breast cancers expressing the estrogen receptor (ER) are more likely to co-express AR compared to ER-negative cancers (56.0% versus 28.1%, P < 0.001). In addition, we found that AR expression is correlated with increased DFS in patients with luminal breast cancer (P < 0.001), and decreased DFS in TNBC (triple negative breast cancer, P = 0.014). In addition, patients with HR+ tumors (Hormone receptor positive tumors) expressing low levels of AR have the lowest DFS among all receptor combinations. We also propose a novel prognostic model using AR receptor status, BRCA1, and present data showing that our model is more predictive of disease free survival compared to the traditional TMN staging system.

Keywords: BRCA1; TNBC; androgen receptor; breast cancer; hormone receptor.

Figure 1. The prognostic role of AR alone in different population and stratified by joint hormone receptor (HR) status

Cumulative Disease-free Survival(DFS) curves of a. all patients (n = 407), b. Luminal subtype patients (n = 185), c. TNBC patients (n = 137), d. HER2 positive patients (n = 85), e. combinations of AR and HR status.

Figure 2. Prognostic value of the AR in TNBC patients was improved by combining BRCA1 status

a. Cumulative Disease-free Survival(DFS) curves of TNBC patients by BRCA1 status. b. Kaplan-Meier estimates of DFS according to AR and BRCA1 statuses in TNBC patients (log rank P = 0.062) c. ROC curves assessing the distinct performances of the combined and the traditional models for predicting the DFS in the TNBC cohort. Variables for the traditional model include TNM stage only. AR and BRCA1 were added in the combined model. p < 0.001 for AUC comparison.