Paving the path ForwARd: Advances and challenges in androgen receptor targeting in breast cancer

Abstract

The role of androgen receptors (AR) in breast cancer is crucial for preclinical and clinical research. While AR-targeted therapy is a standard treatment for prostate cancer, the application of this therapeutic strategy to breast cancer has not been established. Indeed, AR is expressed in around 60-90% of breast cancers, making it imperative that we learn more about its prognostic and predictive impacts and targeting potential in breast cancer. Over the past decade, AR-targeted therapies ─ including AR antagonists and selective AR modulators ─ have shown promise in breast cancer treatment. However, an incomplete understanding of AR's role across breast cancer subtypes hinders clinical application. The lack of standardized AR expression thresholds further complicates patient selection, underscoring the urgent need for biomarker-driven strategies to optimize AR-targeted approaches in breast cancer. In this review, we provide an overview of a clinical perspective of AR in breast cancer by discussing AR biology, AR as a biomarker, and AR-targeted therapy development. We present our review with a particular emphasis on the distinct roles of AR in ER-positive (ER+) and ER-negative (ER-) breast cancer subtypes. Finally, the paper addresses the hurdles that have impeded the development of a robust clinical landscape for AR-targeted therapies and possible solutions for overcoming these challenges.

Keywords: Androgen receptor; Androgen receptor-targeted therapy; Breast cancer.