Androgen receptor gene expression in primary breast cancer

Neelima Vidula,Christina Yau,Hope S Rugo,Denise Wolf

doi:10.1038/s41523-019-0142-6

Neelima Vidula, Christina Yau + Show 2 more

Open Access

https://doi.org/10.1038/s41523-019-0142-6

Copy DOI

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.

Highlights

Breast cancer has conventionally been classified based on the presence or absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), recent studies have indicated that the genomic landscape of breast cancer extends far beyond these 3 receptors.[1]
It is likely that varying subtypes within each of the conventional types of breast cancer (hormone receptor (HR) positive, HER2+, triple-negative breast cancer (TNBC)) may have different clinical and prognostic features, and androgen receptor (AR) expression may factor into this heterogeneity, across breast cancer subtypes
We explored gene correlations with AR and selected other genes involved in the development of breast cancer, using three publically available databases including I-SPY 1 (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis),[6,7] METABRIC,[4] and The Cancer Genome Atlas (TCGA).[8]

Summary

INTRODUCTION

Breast cancer has conventionally been classified based on the presence or absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), recent studies have indicated that the genomic landscape of breast cancer extends far beyond these 3 receptors.[1]. Lehmann and colleagues identified a subtype of triple-negative breast cancer (TNBC) characterized by the presence of the androgen receptor (AR) and expression of other luminal genes termed the luminal-androgen receptor (LAR) subtype. This expression-based subtype was subsequently confirmed by other authors.[1,2]. We evaluated associations between AR gene expression in primary breast cancer, clinical characteristics, and patient outcomes in a well characterized subset of patients with early stage breast cancer in the I-SPY 1 cohort. We explored gene correlations with AR and selected other genes involved in the development of breast cancer, using three publically available databases including I-SPY 1 (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis),[6,7] METABRIC,[4] and The Cancer Genome Atlas (TCGA).[8]

RESULTS

DISCUSSION

CODE AVAILABILITY