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.
Highlights
Breast cancer (BC) is the most common tumor in the female population [1]
Hormone receptor (HR) -positive patients are being treated with hormonal therapy, while HER 2-positive patients are being treated with humanized monoclonal antibodies, exhibiting promising results
The androgen receptor is expressed in more than 70% of primary breast cancers; usually, its expression is correlated to ERα and progesterone receptor (PgR)
Summary
Breast cancer (BC) is the most common tumor in the female population [1] It is characterized by heterogeneity at the molecular and clinical levels. Cytotoxic chemotherapy is the main systemic therapy for Triple-Negative Breast Cancers (TNBCs), a subset of basal-like tumors which is defined by the lack of therapeutic targets, such as HR and HER 2 [5]. AR disassociates from heat shock proteins, gets activated, and forms dimers These dimers translocate to the nucleus, binding to androgen-responsive elements (AREs) within target genes, causing modulations in DNA transcription. Estrogens play a predominant role in female breast development, androgens are indispensable in this process. It has been shown that androgens inhibit the growth of breast tissue [16], revealing the fundamental role of AR signaling in normal breast tissue development
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