Harnessing a Different Dependency: How to Identify and Target Androgen Receptor-Positive Versus Quadruple-Negative Breast Cancer

The androgen receptor (AR) is a promising therapeutic target for a subset of triple-negative breast cancers (TNBCs) in which AR is expressed. However, the mechanistic action of AR and the degree to which primary and metastatic tumors depend on AR, both before and after conventional treatment, remain to be defined. We discuss preclinical and clinical data for AR+ TNBC, the difficulties in monitoring AR protein levels, new methods for determining AR status, the influence of AR on stemness in the context of TNBC, the role of combined inhibition of sex steroid production and AR, and the role of AR in regulation of the immune system. Although the exact role of AR in subsets of TNBC is still being characterized, new therapies that target AR and the production of androgens may provide additional options for patients with TNBC for whom chemotherapy is currently the sole treatment option