Targeting androgen receptors in patients with metastatic breast cancer

Purpose of review This review aims to summarize the current clinical evidence and future perspectives on the use of antiandrogen therapies in metastatic breast cancer, focusing on hormone receptor-positive and triple-negative subtypes, expressing androgen receptor (AR). We discuss recent clinical trials evaluating AR-targeted agents and explore mechanisms of resistance and novel therapeutic strategies. Recent findings Clinical trials of androgen-targeting have shown modest activity in AR-positive metastatic breast cancer, with variable disease control rates and progression-free survival depending on AR expression levels, intrinsic AR-dependency and tumor subtype. Combination therapies targeting AR alongside pathways like CDK4/6 and PI3K/AKT/mTOR appear promising in overcoming therapeutic resistance. New-generation agents, including PROTACs, nonligand-binding domain AR inhibitors and epigenetic modulators offer innovative approaches to target AR signalling. Summary Despite encouraging preclinical data, antiandrogen therapies have not demonstrated robust strong clinical efficacy in metastatic, AR-positive breast cancer, and their use in the clinical practice is still very limited. Improved patient selection using validated predictive biomarkers is crucial. Combination regimens and next-generation AR-targeting agents represent the future direction to overcome resistance and optimize therapeutic outcomes in AR-driven breast cancers.