A Closer Look at the Androgen Receptor (AR)- positive and AR-negative Metastatic Triple-Negative Breast Cancer: Can We Apply Novel Targeted Therapeutics?

Based on the androgen receptor (AR) expression, triple-negative breast cancer (TNBC) (that is estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) negative), can further be divided into AR-negative TNBC (also known as quadruple-negative breast cancer (QNBC), a more frequent TNBC subtype) and AR-positive TNBC. The paucity of treatment targets makes QNBC very difficult to manage. Moreover, in the absence of AR expression, many breast cancers (BCs) often display aggressive behavior, leading to negative outcomes in afflicted women. At present, some novel therapeutic targets have emerged, and hopefully, the relevant targeted strategies will improve the survival of patients with QNBC. This chapter briefly outlines the main TNBC subtypes and focuses on the AR expression (its presence vs. absence), and potential treatment approaches, including AR antagonists (ARA). In addition, this chapter overviews certain molecular characteristics of TNBC and presents recently approved targeted therapies. 

Keywords: Androgen receptor (AR), AR antagonists (ARA), Antibody drug conjugate (ADC), Immune checkpoint inhibitors (ICI), Poly ADP-ribose polymerase (PARP) inhibitors, Quadruple-negative breast cancer (QNBC), Triple-negative breast cancer (TNBC).