Molecular apocrine (MA) breast cancers are a highly aggressive, estrogen receptor-α (ERα) negative subtype that have poor prognosis and limited therapeutic options. MA tumours express high levels of the androgen receptor (AR) and genes known to be regulated by AR in prostate cancers. However, the role of AR in promoting growth of MA breast cancer remains equivocal, with preclinical data suggesting both proliferative and anti-proliferative effects. We hypothesised that differential AR-mediated growth effects are driven by differential interactions with key co-regulatory factors in the transcription complex that convert AR from an inhibitor to a transactivator of critical growth regulatory genes. Two MA breast cancer cell lines were investigated: MDA-MB-453 and MFM223. MDA-MB-453 cells are growth stimulated and MFM223 cells growth inhibited by treatment with the most potent natural androgen, 5α-dihydrotestosterone (DHT). Using an unbiased proteomic approach to detect AR interacting proteins, we identified the transcription factor activating protein-2β (TFAP-2β) as a candidate factor of interest. TFAP-2β protein levels were highly expressed in MDA-MB-453 cells but were not detectable in MFM-223 cells. Using several proteomic approaches, we validated the interaction between AR and TFAP-2β in MDA-MB-453 cells, which was enhanced by treatment with DHT. Silencing TFAP-2β induced apoptosis in MDA-MB-453 cells and decreased protein levels of the oncogenes MYC and HER2. Conversely, ectopic overexpression of TFAP-2β in MFM223 cells reversed DHT-induced growth inhibition. We also showed that in vivo growth of genetically defined organoids established from human mammary epithelial cells transformed with TFAP-2β and classic mammary oncogenes have apocrine histology and are growth stimulated by androgenic treatment in vivo. Our findings suggest that TFAP-2β is a critical regulator of the MA breast cancer phenotype and a determinant of oncogenic AR signalling. Hence, TFAP-2β may be a useful biomarker to determine whether patients with MA breast cancer would benefit from anti-androgen therapy.