Androgen receptor in estrogen receptor positive breast cancer: Beyond expression

Area of Science:

• Oncology
• Endocrinology
• Molecular Biology

Background:

• Novel therapies have improved breast cancer (BC) treatment and patient survival, particularly for estrogen receptor (ER)-positive BC.
• Resistance to these therapies, either de novo or acquired, remains a significant clinical challenge.
• The androgen receptor (AR) plays a complex role in ER-positive BC, with potential implications for treatment resistance.

Purpose of the Study:

• To investigate the role of androgen receptor (AR) and estrogen receptor (ER) cross-talk in luminal-like breast cancer (BC).
• To identify potential biomarkers for selecting BC patients who may benefit from combination therapies targeting both ER and AR.

Main Methods:

• Review of preclinical and clinical studies examining AR and ER interactions in BC.
• Analysis of AR expression levels and AR:ER ratios in relation to treatment response.
• Exploration of the potential efficacy of AR-inhibitors in specific BC subtypes.

Main Results:

• Androgen receptor (AR) is expressed in a majority of BC cases, including most ER-positive tumors, and is often associated with a favorable prognosis.
• High AR expression, particularly an elevated AR:ER ratio, may be linked to resistance to hormonal therapies in ER-positive BC.
• Some ER-positive BC patients may not benefit from current AR-inhibitor strategies, necessitating further patient stratification.

Conclusions:

• The cross-talk between AR and ER is a critical factor in luminal-like BC, influencing treatment response and resistance.
• Identifying biomarkers to predict response to AR-targeted therapies is crucial for optimizing treatment strategies.
• Combination therapy with ER and AR inhibitors holds promise, but patient selection based on specific biomarkers is essential for maximizing clinical benefit.