Improving HER2 testing reproducibility in HER2-low breast cancer

Area of Science:

• Oncology
• Pathology
• Biomarker Analysis

Background:

• Human Epidermal growth factor Receptor 2 (HER2) is a key biomarker in breast cancer diagnostics.
• Current HER2 assessment involves immunohistochemistry (IHC) and in situ hybridization (ISH) for specific scores.
• Emerging antibody-drug conjugates show efficacy in HER2-low expressing breast cancers, expanding treatment possibilities.

Purpose of the Study:

• To highlight the evolving landscape of HER2 testing in breast cancer.
• To emphasize the clinical significance of discriminating between HER2-zero, HER2-low, and HER2-positive tumors.
• To underscore the importance of refining HER2 testing methodologies for new therapeutic strategies.

Main Methods:

• Review of current HER2 testing protocols including IHC and ISH.
• Analysis of the impact of novel HER2-directed therapies on treatment paradigms.
• Discussion of preanalytical and analytical factors influencing HER2 test sensitivity and reproducibility.

Main Results:

• Novel antibody-drug conjugates are effective against HER2-low expressing breast cancers (IHC 1+ or ISH-negative IHC 2+).
• Resistance to anti-HER2 therapies remains a significant clinical challenge.
• Precise discrimination of HER2 expression levels is critical for patient stratification.

Conclusions:

• The accurate assessment of HER2 status is increasingly vital due to new therapeutic options.
• Optimization of HER2 testing criteria, guidelines, and quality control is essential.
• Addressing preanalytical and analytical variables in HER2 testing will improve patient outcomes and therapeutic opportunities.