Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer

Abstract

This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.

Keywords: androgen antagonist; androgen receptor; triple-negative breast cancer.

Figure 1

Mechanism of androgen receptor (AR) activation. Figure 1 represents how AR is activated by testosterone or dihydrotestosterone in a cell. 1. When AR is inactive, it is bound to heat-shock proteins (HSP). 2. Circulating androgens (e.g., testosterone and dihydrotestosterone) bind to C terminal ligand-binding domain and cause a conformational change of AR, displacing HSP. 3. Afterwards, dimerization of AR and phosphorylation of its tyrosine kinases occurs. This change causes 4. translocation of the complex to the nucleus where a DNA binding complex binds to androgen-responsive elements and transcription complex is formed. AR—androgen receptor HSP—heat-shock protein T; DHT—testosterone, dihydrotestosterone; P—phosphate group RNA pol II complex—RNA polymerization complex; GTF—general transcription factors; CA—coactivators.