Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Sep 20:10:4675-4685.
doi: 10.2147/OTT.S126051. eCollection 2017.

Targeting the androgen receptor in triple-negative breast cancer: current perspectives

Alain Mina  1 , Rachel Yoder  2 , Priyanka Sharma  1
Affiliations
Review

Targeting the androgen receptor in triple-negative breast cancer: current perspectives

Alain Mina et al. Onco Targets Ther. .

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR) signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies. Recent advances in our understanding of androgenic signaling in TNBC, along with the identification of interacting pathways, are allowing development of the next generation of clinical trials with AR inhibitors. As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition.

Keywords: androgen signaling; biomarkers; prognosis; targeted therapy; triple-negative breast cancer.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Ligand-dependent activation of androgen response elements. Notes: Testosterone enters the cytoplasm, where it is reduced to DHT by 5α-reductase. AR is released from heat shock proteins and activated by binding DHT. Activated AR dimerizes and translocates to the nucleus, where it recruits transcription factors to an ARE in the sequence of an androgen-regulated gene. Transcription of many androgen-regulated genes contributes to breast development and/or tumorigenesis.
Figure 2
Figure 2
Incidence of TNBC by TNBC type-4 classification. Note: Adapted from Lehmann BD, Jovanovic B, Chen X, et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PLoS One. 2016;11(6):e0157368. Abbreviations: TNBC, triple-negative breast cancer; BL1, basal-like 1; BL2, basal-like 2; M, mesenchymal; LAR, luminal androgen receptor-like; UNC, unclasssified.
Figure 3
Figure 3
Current and future landscape of AR pathway targeting in breast cancer. Abbreviations: AR, androgen receptor; TNBC, triple-negative breast cancer; CDK, cyclin-dependent kinase; CYP17, cytochrome P450 17α-hydroxylase/17,20-lyase; LAR, luminal androgen receptor-like; mTOR, mechanistic target of rapamycin; P13K, phosphatidylinositol-3-kinase.
See this image and copyright information in PMC

References

    1. American Cancer Society . Cancer Facts and Figures 2017. Atlanta, GA: American Cancer Society; 2017.
    1. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–4434. - PubMed
    1. Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer registry. Cancer. 2007;109(9):1721–1728. - PubMed
    1. Loibl S, Muller BM, von Minckwitz G, et al. Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2011;130(2):477–487. - PubMed
    1. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–2767. - PMC - PubMed