The Role of the Androgen Receptor Signaling in Breast Malignancies

Breast cancer (BrCa) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. Despite the development of novel therapeutic modalities, triple-negative breast cancer (TNBC) remains an incurable disease. Androgen receptor (AR) is widely expressed in BrCa and its role in the disease may differ depending on the molecular subtype and the stage. Interestingly, AR has been suggested as a potential target candidate in TNBC, while sex hormone levels may regulate the role of AR in BrCa subtypes. In the presence of estrogen receptor alpha (ERa), AR may antagonize the ERa-induced effects, whereas in the absence of estrogens, AR may act as an ER alpha-mimic, promoting tumor. Thus, depending on the BrCa microenvironment, both agonists and antagonists of the AR have been suggested as therapeutic approaches. Herein, we review the role of AR signaling in BrCa and the molecular cross-talk mechanisms with other molecules/ pathways, as well as its therapeutic implications in the different subtypes of the disease.