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HER2-positive carcinoma of breast — Clinical Guidelines

Overview

HER2-positive breast cancer is a subtype characterized by the overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) protein 1. This subtype has historically been associated with aggressive tumor behavior but is targetable with specific therapies 1 2. A newer category, HER2-low breast cancer, is also emerging as a targetable subset based on novel antibody-drug conjugates 2.

Diagnosis

HER2 testing is recommended for invasive breast cancers 1.

Testing typically involves immunohistochemistry (IHC) for protein overexpression and in situ hybridization (ISH) for gene amplification 1.

The 2018 ASCO-CAP recommendations for HER2 testing are affirmed 1.

HER2-low breast cancer is defined by IHC scores of 1+ or 2+ without amplification by ISH 1 2.

Limited data exist for tumors testing IHC 0 1.

Management

Therapies targeting HER2 signaling are used for HER2-positive breast cancer 1.

Newer antibody-drug conjugates (ADCs) targeting HER2 are active against breast cancers with HER2 protein overexpression or gene amplification 1.

Trastuzumab deruxtecan is indicated for tumors with IHC 1+ or 2+ without ISH amplification 1.

Key Recommendations

Affirm the 2018 ASCO-CAP recommendations for HER2 testing in breast cancer 1. (Evidence: Expert opinion)

HER2 testing should focus on identifying HER2 protein overexpression or gene amplification to guide therapy 1. (Evidence: Expert opinion)

Consider trastuzumab deruxtecan for breast cancers with IHC 1+ or 2+ without ISH amplification, as this subset is now targetable 1. (Evidence: Expert opinion)

References

1 Wolff AC, Somerfield MR, Dowsett M, Hammond MEH, Hayes DF, McShane LM et al.. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2023. link 2 Tarantino P, Viale G, Press MF, Hu X, Penault-Llorca F, Bardia A et al.. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology 2023. link 3 Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL et al.. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2020. link

HER2-positive carcinoma of breast

Overview

Diagnosis

Management

Key Recommendations

References

Original source