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Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology-College of American Pathologists Guideline Update

Purpose: To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.

Methods: The 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 constituted a signal 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 antibody-drug conjugates. 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, although 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.

 

Comments:

Summary: The American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) has conducted a review of the existing recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The purpose was to determine whether the recommendations needed to be updated in light of new developments regarding antibody-drug conjugates targeting HER2.

The systematic literature review conducted by the Update Panel identified 173 abstracts. However, upon reviewing the potential publications, none of them provided sufficient evidence to warrant revising the existing recommendations.

Therefore, the 2018 ASCO-CAP recommendations for HER2 testing are affirmed.

The discussion section of the update acknowledges a new indication for trastuzumab deruxtecan, which is effective against breast cancers that lack HER2 protein overexpression or gene amplification. This new indication is relevant when HER2 is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization.

Although there is limited clinical trial data on tumors that tested IHC 0 (no HER2 expression), the evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. As a result, it is now important to distinguish between IHC 0 and 1+ results.

While it is premature to create new result categories for HER2 expression, the update provides best practice recommendations for distinguishing between IHC 0 and 1+ results. The update also introduces a new HER2 testing reporting comment to highlight the current relevance of these results and the best practices for distinguishing between them.

In conclusion, the update affirms the previous HER2 testing recommendations and provides additional guidance for distinguishing between IHC 0 and 1+ results in light of the new indications for trastuzumab deruxtecan.

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S9795 Deruxtecan

Deruxtecan is an ADC drug-linker conjugate composed of the cleavable glycine–glycine–phenylalanine–glycine tetrapeptide-based linker, a self-immolative amino methylene spacer, and a novel topoisomerase 1 inhibitor payload that is a derivative of exatecan (DX-8951).

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