Targeting the androgen receptor in triple-negative breast cancer Journal Article


Authors: Gucalp, A.; Traina, T. A.
Article Title: Targeting the androgen receptor in triple-negative breast cancer
Abstract: Triple-negative breast cancer represents approximately 15%-20% of all newly diagnosed breast cancers, but it accounts for a disproportionate number of breast cancer-related deaths each year. Owing to the lack of estrogen, progesterone, and human epidermal growth factor receptor 2 expression, patients with triple-negative breast cancer do not benefit from generally well-tolerated and effective therapies targeting the estrogen and human epidermal growth factor receptor 2 signaling pathways and are faced with an increased risk of disease progression and poorer overall survival. The heterogeneity of triple-negative breast cancer has been increasingly recognized and this may lead to therapeutic opportunities because of newly defined oncogenic drivers and targets. A subset of triple-negative breast tumors expresses the androgen receptor (AR) and this may benefit from treatments that inhibit the AR-signaling pathway. The first proof-of-concept trial established activity of the AR antagonist, bicalutamide, in patients with advanced AR+ triple-negative breast cancer. Since that time, evidence further supports the activity of other next-generation AR-targeted agents such as enzalutamide. Not unlike in estrogen receptor-positive breast cancer, mechanisms of resistance are being investigated and rationale exists for thoughtful, well-designed combination regimens such as AR antagonism with CDK4/6 pathway inhibitors or PI3K inhibitors. Furthermore, novel agents developed for the treatment of prostate cancer, which reduce androgen production such as abiraterone acetate and seviteronel, are being tested as well. This review summarizes the underlying biology of AR signaling in breast cancer development and the available clinical trial data for the use of anti-androgen therapy in the treatment of AR+ triple-negative breast cancer. © 2016 Elsevier Inc.
Keywords: androgen receptor; abiraterone acetate; bicalutamide; triple negative breast cancer; enzalutamide; seviteronel
Journal Title: Current Problems in Cancer
Volume: 40
Issue: 2-4
ISSN: 0147-0272
Publisher: Mosby Elsevier  
Date Published: 2016-03-01
Start Page: 141
End Page: 150
Language: English
DOI: 10.1016/j.currproblcancer.2016.09.004
PROVIDER: scopus
PUBMED: 27816190
PMCID: PMC5580391
DOI/URL:
Notes: Review -- Export Date: 3 January 2017 -- Source: Scopus
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  1. Ayca Gucalp
    113 Gucalp
  2. Tiffany A Traina
    250 Traina