Androgen Receptor in Breast Cancer: From Bench to Bedside

Abstract

Breast cancer (BC) is one of the most common malignancies and the leading cause of cancer-related mortality in women. Androgen receptor (AR) is frequently expressed in diverse BC subtypes. Accumulating evidence has revealed that AR might be a predictive or prognostic factor and a drug target in BC. AR expression and AR pathways differ in various BC subtypes, thereby resulting in controversial inferences on the predictive and prognostic value of AR. Herein, we summarized the roles of AR in different BC subtypes and AR-targeting therapies based on preclinical and clinical studies. Moreover, we highlighted the possible efficacy of a combination therapy via exploiting the AR-related mechanisms and the research on therapeutic resistance.

Intrinsic Subtypes and Androgen Receptor Gene Expression in Primary Breast Cancer. A Meta-Analysis

“…Accordingly, high AR mRNA levels observed in the datasets studied here give support to the insight that, in HER2+ tumors, the cooperation between AR and HER2 promotes ERK activation that regulates both HER2 and AR gene expression. As a consequence, there is a positive feedback loop [ 55 , 56 ] that may stimulate cell proliferation and the worse clinical outcomes usually observed in HER2+ BCs. AR mRNA expression in these cases is consistent with analyses performed using both BC molecular subtypes and IHC-surrogate subtypes, showing that AR mRNA levels are higher in HER2-enriched tumors compared to basal-like and TNBC tumors, respectively.…”

Relevance of the 21-gene expression assay in male breast cancer: A systematic review and meta-analysis

“…Like the ER, AR is a member of the steroid-hormone receptor superfamily and can be expressed in high concentrations on breast cancer tissue [ 31 , 32 ]. Overall, 90% of MBC patients express AR-receptors on the surface of their tumour cells [ 29 , 33 ], which may serve as potential therapeutic targets [ 34 ], as is routinely observed in the treatment of prostatic adenocarcinoma [ 35 ]. ER-positive breast cancers are significantly more likely to be AR-positive than ER-negative tumours [ 36 ], with some studies suggesting AR status is a correlate of ER-alpha/PgR signaling [ 37 ].…”

Obesity and Androgen Receptor Signaling: Associations and Potential Crosstalk in Breast Cancer Cells

“…Among them, the luminal AR (LAR) subtype, is associated with a transcriptomic profile enriched for AR expression signaling pathways and for having a luminal-like gene profile [ 89 , 143 , 150 , 151 ]. LAR tumors are characterized to be highly aggressive [ 152 , 153 ], which has emphasized the need for clarifying the role of AR in BC and promoted the development of several AR antagonists that are currently being tested in multiple clinical trials alone or in combination with other treatment strategies for ER− BC, which have been comprehensively reviewed by other authors [ 108 , 154 , 155 , 156 ]. To note, a phase II clinical trial comprising 424 TNBC patients, showed bicalutamide provide good results and have a considerable CBR at 6 months (19%) [ 157 ].…”