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.