The evolving role of receptors as predictive biomarkers for metastatic breast cancer

ABSTRACT

Introduction: In breast cancer, estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are essential biomarkers to predict response to endocrine and anti-HER2 therapies, respectively. In metastatic breast cancer, the use of these receptors and targeted therapies present additional challenges: temporal heterogeneity, together with limited sampling methodologies, hinders receptor status assessment, and the constant evolution of the disease invariably leads to resistance to treatment.

Areas covered: This review summarizes the genomic abnormalities in ER and HER2, such as mutations, amplifications, translocations, and alternative splicing, emerging as novel biomarkers that provide an insight into underlying mechanisms of resistance and hold potential predictive value to inform treatment selection. We also describe how liquid biopsies for sampling of circulating markers and ultrasensitive detection technologies have emerged which complement ongoing efforts for biomarker discovery and analysis.

Expert commentary: While evidence suggests that genomic aberrations in ER and HER2 could contribute to meeting the pressing need for better predictive biomarkers, efforts need to be made to standardize assessment methods and better understand the resistance mechanisms these markers denote. Taking advantage of emerging technologies, research in upcoming years should include prospective trials incorporating these predictors into the study design to validate their potential clinical value.

KEYWORDS:

• biomarkers
• metastatic breast cancer
• hormone receptors
• ER
• HER2

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.