Effect of MDV3100, a novel androgen receptor signaling inhibitor, on cell proliferation and tumor size in an apocrine breast cancer xenograft model.

3072 Background: MDV3100, a new androgen receptor (AR) signaling inhibitor, has demonstrated therapeutic effects in men with post-docetaxel prostate cancer (AFFIRM). AR is also expressed in the majority of breast cancers. Molecular profiling of estrogen receptor negative (ER-) breast cancer classifies this disease into basal and molecular apocrine subtypes. Apocrine breast cancer represents ~50% of ER- tumors and is characterized by a steroid response gene signature that includes AR expression. Here we report the effects of MDV3100 on the growth of the ER-/AR+ breast cancer cell line MDA-MB-453 in tissue culture and in an in vivo xenograft mouse model. Methods: MDA-MB-453 cells were maintained in 5% complete or 5% charcoal-stripped serum supplemented with dihydrotestosterone (CSS-DHT). The DHT induced nuclear translocation of AR was determined by subcellular fractionation followed by western blot. AR target gene expression was measured by qPCR. To generate a mouse xenograft model, 5-6 wk old female NOD-SC...