Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer
Guideline Status: Current
Published Online: June 7, 2023
Last Updated: July 31, 2023
Published online before print June 7, 2023. DOI: 10.1200/JCO.22.02864
Antonio C. Wolff, Mark R. Somerfield, Mitchell Dowsett, M. Elizabeth Hammond, Daniel F. Hayes, Lisa M. McShane, Thomas J. Sapher, Patricia A. Spears, and Kimberly H. Allison.
Purpose
To update ASCO--College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware that a new generation of antibody-drug conjugates (ACDs) targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.
Methods
An Update Panel conducted a systematic literature review to identify signals for updating recommendations.
Results
The search identified 173 abstracts. Of 5 potential publications reviewed, none consiconstitutedgnal for revising existing recommendations.
Recommendations
The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
Discussion
HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 ADCs. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, while it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This Update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences.
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