Androgen Receptor in Breast Cancer—Clinical and Preclinical Research Insights

Abstract

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy among females worldwide. The concordance of more than 70% of AR expression in primary and metastatic breast tumors implies that AR may be a new marker and a potential therapeutic target among AR-positive breast cancer patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. AR exhibits different behavior depending on the breast cancer subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since the prognostic and predictive value of AR positivity remains uncertain, it is difficult to identify and stratify patients that would benefit from AR-targeted therapies. Herein, through a review of preclinical studies, clinical studies, and clinical trials, we summarize the biology of AR, its prognostic and predictive value, as well as its therapeutic implications by breast cancer molecular subtype.

Correlation between Androgen Receptor Expression and Immunohistochemistry Type as Prognostic Factors in a Cohort of Breast Cancer Patients: Result from a Single-Center, Cross Sectional Study

“…Given these data, we consider it is important to correlate the blood androgen levels with the positivity of the AR, moreover the association between increased androgen levels and high BC risk in pre- and postmenopausal patients. We consider that this aspect may be taken into account for the screening of BC [ 52 , 53 , 54 ].…”

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer

“…It is reported that AR is overexpressed in 10–41% of TNBCs [ 25 , 26 ]. However, the clinical and prognostic value of AR expression is still controversial [ 27 ], whereas few phase II studies have evaluated the clinical value of AR blockade in AR+ mTNBC, showing modest results [ 28 ]. Results from ongoing studies evaluating different AR blocking agents in early and mTNBC are still awaited [ 29 , 30 ].…”

Triple‑negative breast cancer therapy: Current and future perspectives (Review)

“…AR can also be activated in a ligand-independent manner through crosstalk with key signaling pathways, including PI3K/AKT and ERK (84). AR is involved in cell cycle regulation and the epithelial-to-mesenchymal transition (EMT) (85,86). AR has emerged as a new biomarker and a potential therapeutic target in TNBC.…”