Androgen Receptor Function and Androgen Receptor-Targeted Therapies in Breast Cancer: A Review

JAMA Oncol. 2017 Sep 1;3(9):1266-1273. doi: 10.1001/jamaoncol.2016.4975.


Importance: The androgen receptor (AR) pathway is emerging as a potential therapeutic target in breast cancer. To date, AR-targeted drugs have been approved only for treatment of prostate cancer; however, AR-targeted treatment for breast cancer is an area of active investigation. Through review of preclinical studies, retrospective clinical studies, and clinical trials, we examined the biology of AR and AR-related pathways, the potential for AR-targeted therapies in breast cancer, and potential biomarkers for AR-targeted treatments.

Observations: The rate of AR positivity in breast cancer is about 60% to 80%. Biologically, the AR pathway has cross-talk with several other key signaling pathways, including the PI3K/Akt/mTOR and MAPK pathways, and with other receptors, including estrogen receptor and human epidermal growth factor receptor-2. The value of AR positivity as a prognostic marker has not yet been defined. Androgen receptor-targeted therapies, including AR agonists, AR antagonists, and PI3K inhibitors, have shown promising results in clinical trials in patients with breast cancer, and combinations of AR-targeted therapies with other agents have been investigated for overcoming resistance to AR-targeted therapies. Biomarkers to stratify patients according to the likelihood of response to AR-targeted drugs are yet to be established. Potential biomarkers of response to AR inhibitors include AR phosphorylation and AR gene expression.

Conclusions and relevance: Androgen receptor-targeted treatments for breast cancer are in development and have shown promising preliminary results. In-depth understanding of AR and AR-related signaling pathways would improve the treatment strategies for AR-positive breast cancer. Further preclinical and clinical studies of AR-targeted drugs alone and in combination with other drugs are justified and warranted to clarify the biology of AR and inform the development of AR-targeted therapies to improve survival outcome in patients with breast cancer.

Publication types

  • Review

MeSH terms

  • Androgen Receptor Antagonists / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression
  • Humans
  • Molecular Targeted Therapy
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Receptor, ErbB-2 / analysis
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Receptors, Estrogen / analysis
  • Signal Transduction


  • Androgen Receptor Antagonists
  • Biomarkers, Tumor
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Androgen
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2