Androgen treatment inhibits ER signaling in ER+/AR+ breast cancer cell lines, and AR expression is associated with improved survival for this subtype in epidemiologic studies.
In the prospective Nurses' Health Study cohort, we evaluated alcohol consumption and breast cancer risk by individual tumor marker expression (i.e., ER, progesterone receptor [PR], AR, and IR) while controlling for other markers and also assessed the joint effect of these receptors.
The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours.
Treatment of MDA-MB-453 with CREBBP/EP300 bromodomain inhibitors downregulates the expression of an AR-dependent signature distinctive of breast cancer tumors that express AR and causes a decrease in H3K27ac levels at AR-binding sites.
Other steroid hormone receptors such as progesterone receptor (PR) and androgen receptor (AR) are emerging as additional prospective targets in breast cancer.
<b>Purpose:</b> Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER<sup>+</sup>) breast cancer cells and were used to treat breast cancer, eliciting favorable response.
Phase Ib patients (ER+ or TNBC) with AR+ breast cancer received 160 mg enzalutamide in combination with taselisib to determine dose-limiting toxicities and the maximum tolerated dose (MTD).
Unlike canonical AR signaling which is inhibited by enzalutamide, non-canonical AR activity is not effectively antagonized by enzalutamide, and this has important implications in the design of future AR-targeted clinical trials in endocrine-resistant breast cancer.
The present data indicate that androgens can down-regulate bcl-2 protooncogene levels via an androgen receptor-mediated mechanism, thus providing a novel mechanism for their known inhibitory effect on breast cancer cell growth.
This case report supports the literature regarding the possible association between Leydig cell tumor and androgen-receptor-positive breast cancer development.
Androgens and AR have been reported to facilitate tumor stemness in some cancers; a process which may be mediated through genomic or non-genomic actions of the AR, with the latter mechanism being relatively unexplored in breast cancer.
These data represent the rationale for AR-targeting treatment as a potentially new target therapy in breast cancer subset using androgen agonists in some AR-positive/ER-positive tumors, AR antagonists in triple-negative/AR-positive tumors and in combination with anti-HER2 agents or with other signaling pathways inhibitors (including PI3K/MYC/ERK) in HER2-positive/AR-positive tumors.
Furthermore, expression of estrogen receptor (ER) is a high relevant molecular event with key therapeutic implications in breast cancer, and androgen receptor (AR) signaling is involved in the pathogenesis of breast cancer and represents a novel target with crescent importance in this disease.