The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Androgen Receptor in Breast Cancer:  potential utility as a prognostic indicator or therapeutic target in breast cancer (#138)

Jennifer Richer 1
  1. University of Colorado, Aurora, CO, United States

Androgen receptor (AR) has long served as a therapeutic target for treatment of prostate cancer and drugs exist that either bind to AR directly and serve as agonists or antagonists, or work by inhibiting enzymes involved in androgen synthesis. In breast cancer (BC), AR is even more widely expressed across subtypes than estrogen or progesterone receptors (ER and PR) as it is expressed in a portion of triple negative BC (TNBC) (~20-50%), HER2+ disease (~60%) and ~91% of ER+ tumors. The role of AR in the various subtypes of BC is controversial and context dependent, varying with hormonal milieu (menopausal status) of the patient, levels of the other steroid receptors in tumors, treatment, and disease progression. While preclinical models demonstrate that optimal ER activity is dependent on nuclear AR, ligand activated AR can also inhibit ER activity since in the presence of their cognate ligands, the two receptors compete to regulate some of the same genes. Tamoxifen has partial agonist activity that increases AR, and the selective pressure of tamoxifen or estrogen deprivation (aromatase inhibitors) in post-menopausal women with BC can lead to increased dependence on AR. AR upregulates the growth factor receptors HER2 and HER3 and also upregulates amphiregulin, a ligand for EGFR. In TNBC, AR can substitute for ER, drive the “luminal AR/ LAR” phenotype and support the survival of such tumors. AR regulates genes involved in tumor metabolism as well as anti-stress, pro survival genes/proteins. AR+ TNBC are slower growing, but consequently respond relatively poorly to chemotherapy and AR is positively associated with node positive disease. This lecture will summarize recent clinical trials with various AR modulating drugs as well as agents that inhibit androgen synthesis.