# The Role of Androgen Receptor and Antiandrogen Therapy in Breast Cancer: A Scoping Review

## TL;DR

This review explores how the androgen receptor influences breast cancer and how blocking it might help some patients, especially those with limited treatment options.

## Contribution

The paper provides a comprehensive scoping review of the androgen receptor's role in breast cancer and antiandrogen therapy, emphasizing precision medicine approaches.

## Key findings

- The androgen receptor may slow tumor growth in some breast cancers but support it in others.
- Antiandrogen drugs show modest benefits, mainly in carefully selected patients.
- Resistance to antiandrogen therapy and the need for better biomarkers remain significant challenges.

## Abstract

Breast cancer is not one disease but many different types that behave differently and need different treatments. Most therapies target the female hormones, estrogen and progesterone, but another hormone receptor, called the androgen receptor, is also found in many breast cancers, including some aggressive tumors that lack the usual treatment targets. This review summarizes what is currently known about how the androgen receptor affects breast cancer development and how medicines that block it may help certain patients. We describe how the androgen receptor works inside cells, why it may slow tumor growth in some breast cancers but support growth in others, and what clinical studies have reported so far for antiandrogen drugs. Overall, benefits have generally been modest, and responses appear concentrated in carefully selected patients, meaning these treatments are not yet routine care. We also explain why resistance can occur and why better laboratory tests are needed to identify who is most likely to benefit. Finally, we outline future directions, including combining androgen receptor-blocking drugs with other treatments and using modern blood- and tissue-based testing to personalize therapy over time. This work is valuable because it may guide the development of new options for patients with limited choices while helping avoid ineffective treatment.

Breast cancer is a complex and highly heterogeneous disease, and its management is increasingly moving towards the principles of precision medicine. In this context, the androgen receptor (AR) has emerged as a promising therapeutic target, particularly within the challenging subgroup of triple-negative breast cancers (TNBCs) that express it. This scoping review provides a comprehensive and detailed analysis of the multifaceted role of AR in breast cancer. We delve into its intricate molecular structure, its differential function in ER-positive vs. TNBC subtypes, and the detailed molecular mechanisms that govern its activity. We provide a thorough examination of the landmark clinical trials with antiandrogen agents, including not only enzalutamide but also other first- and second-generation compounds, and discuss the emerging data on their efficacy. Furthermore, we will explore the critical challenges that hinder their widespread clinical adoption, such as primary and acquired resistance mechanisms, the need for robust predictive biomarkers, and the heterogeneity of AR expression. Finally, we outline future research directions, focusing on novel combination therapies and the development of next-generation agents and predictive tools to optimize patient selection and improve clinical outcomes.