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Published by American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP)
HER2 testing guidelines focus on identifying protein overexpression or gene amplification to identify patients for HER2-targeted therapies. This update addresses a new indication for trastuzumab deruxtecan for tumors with HER2 IHC 1+ or 2+ without amplification, highlighting the clinical relevance of distinguishing IHC 0 from 1+.
Key Takeaways
Affirms the 2018 ASCO-CAP guidelines. Introduces a new HER2 testing reporting comment to highlight the relevance of IHC 0 versus 1+ results due to new indications for trastuzumab deruxtecan. Outlines best practices to distinguish these differences without creating new formal result categories like 'HER2-Low'.
The 2018 ASCO-College of American Pathologists (CAP) recommendations for HER2 testing are affirmed.
HER2 testing should still be optimized for the predictive purpose of identification of breast cancers with protein over-expression and/or gene amplification who could benefit from therapies aimed at disrupting HER2 signaling pathways.
While it is premature to change reporting terminology for lower levels of HER2 IHC expression (eg, HER2-Low), pathology labs should include a footnote in their HER2 testing reports (IHC and in situ hybridization [ISH]) with a recommended comment explaining treatment eligibility for tumors that are HER2 IHC 3+ or IHC 2+/ISH amplified, versus IHC 1+ or IHC 2+/ISH not-amplified.
HER2 IHC 1+ or 0 results are still both interpreted as HER2-negative (HER2 is not overexpressed) using the previously recommended scoring criteria. Importantly, the semiquantitative IHC score must always be reported as well to ensure patients who meet eligibility criteria for trastuzumab deruxtecan can be identified.
Since eligibility for trastuzumab deruxtecan may hinge around the IHC 0/IHC 1+ threshold, pathologists can make best practice efforts to distinguish IHC 1+ results from 0 by examining slides using standardized criteria, examining at high power (40x), considering a second pathologist review, using controls with a range of protein expression, and paying careful attention to preanalytic conditions.
Medical oncologists can also consider HER2 IHC results on prior or concurrent primary samples (or other metastatic sites) because there may be heterogeneity in HER2 expression levels between samples and because metastatic cancer tissue samples may suffer from preanalytic conditions that are not as well monitored as in primary breast tissue samples.
Clinical Topic
Human Epidermal Growth Factor Receptor 2 (HER2) Testing
Objectives
To update ASCO-CAP recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer and identify patients for therapies that disrupt HER2 signaling.
Target Patient Population
Patients with breast cancer
Diagnostic Criteria
HER2 testing by validated IHC assay scoring algorithm: IHC 3+ (positive), IHC 2+ (equivocal), IHC 1+ (negative), IHC 0 (negative).
Target Providers
Therapeutic Area
Breast CancerGuideline Scope
Difficulty
advanced
Learning Paths