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American Society of Clinical OncologyMedical oncology2023advanced

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

Published by American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP)

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Summary

AI-generated

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+.

breast cancerHER2trastuzumab deruxtecanASCO-CAPmedical oncologyguidelinesrecommendationsIHC 0

Key Takeaways

  • 1
    The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
  • 2
    It is currently premature to change reporting terminology to include categories like 'HER2-Low'.
  • 3
    Pathology labs should include a standard footnote in HER2 testing reports detailing eligibility for therapies targeting non-amplified/non-overexpressed HER2.
  • 4
    Pathologists should adhere to specific best practices to accurately distinguish IHC 1+ from IHC 0 results due to new clinical relevance for treatments like trastuzumab deruxtecan.
  • 5
    Medical oncologists should consider HER2 IHC results on prior or concurrent primary samples due to potential heterogeneity and preanalytic variables.

What's New in This Version

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'.

Key Recommendations

Recommendations

  • REC-1

    The 2018 ASCO-College of American Pathologists (CAP) recommendations for HER2 testing are affirmed.

    Testing

HER2 Immunohistochemistry (IHC) Testing Best Practices Recommendations

  • REC-2

    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.

    Testing
  • REC-3

    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.

    Reporting
  • REC-4

    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.

    Reporting
  • REC-5

    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.

    Testing
  • REC-6

    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 Evaluation

Scope & Objectives

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

Medical oncologistsSurgical oncologistsRadiologistsPathologistsOncology nursesOncology advanced practice providers

Patient Criteria & Setting

Therapeutic Area

Breast Cancer

Guideline Scope

Diagnostic TestingBiomarker Evaluation

Authors & Contributors

Antonio C. WolffMark R. SomerfieldMitchell DowsettM. Elizabeth H. HammondDaniel F. HayesLisa M. McShaneThomas J. SaphnerPatricia A. SpearsKimberly H. Allison

Guideline Features

Flowcharts includedBased on systematic reviewMultidisciplinaryPatient involvement

Learning Context

Difficulty

advanced

Learning Paths

HER2 TestingBreast CancerImmunohistochemistryPathologyOncologyASCO-CAP Guidelines