Best practices for achieving consensus in HER2-low expression in breast cancer: current perspectives from practising...

Area of Science:

• Oncology
• Pathology
• Biomarker Analysis

Background:

• Human epidermal growth factor receptor 2 (HER2) expression is a critical biomarker in breast cancer (BC).
• HER2-negative (HER2-) BC often exhibits low HER2 levels (IHC 1+ or IHC 2+/ISH-), representing a significant therapeutic category.
• Targeted therapy with a new HER2-directed antibody-drug conjugate is available for HER2-low BC.

Purpose of the Study:

• To provide best practices and guidance for achieving consensus in HER2 immunohistochemistry (IHC) scoring for breast cancer (BC).
• To address the challenges in IHC testing and scoring of HER2-low expressing BC.
• To ensure accurate identification of BCs expressing low levels of HER2 for optimal treatment selection.

Main Methods:

• Expert pathologists outline best practices for HER2 IHC scoring in BC.
• A proposed algorithm for assessing HER2 expression using validated IHC assays is presented.
• Guidance incorporates the 2023 American Society of Clinical Oncology and College of American Pathologist guideline update.

Main Results:

• The study details current knowledge and challenges in HER2 IHC testing for BC.
• Best practices are provided for accurate identification of HER2-low BC.
• Examples of challenging HER2 IHC staining cases are included.

Conclusions:

• Accurate HER2 IHC scoring is vital for optimal treatment selection in breast cancer.
• Awareness of HER2 protein expression and its clinical relevance guides targeted therapy decisions.
• This guidance facilitates consistent and reliable HER2 biomarker testing in BC.