Related Experiment Video

Updated: May 30, 2025

Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
08:29

Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells

Published on: May 9, 2025

72

Human Epidermal Growth Factor Receptor 2 Alterations and Prognostic Implications in All Subtypes of Breast Cancers

Arielle L Heeke1, Andrew Elliott2, Kaitlyn O'Keefe1

  • 1Levine Cancer Institute, Atrium Health, Charlotte, NC.

JCO Precision Oncology
|January 31, 2025
PubMed
Abstract

Insights

Alterations in the human epidermal growth factor receptor 2 (HER2) gene, including mutations and fusions, are present in various breast cancer subtypes. These HER2 alterations are linked to a poorer prognosis, especially in metastatic and lobular breast cancers.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The human epidermal growth factor receptor 2 (HER2) gene (ERBB2) plays a crucial role in cell growth and is a target for specific cancer therapies.
  • Understanding the spectrum of ERBB2 alterations in breast cancer is essential for guiding treatment decisions and predicting patient outcomes.

Purpose of the Study:

  • To comprehensively characterize the frequency and types of ERBB2 alterations (mutations, fusions, copy number amplifications) across diverse breast cancer subtypes.
  • To investigate the association between ERBB2 alterations and clinicopathologic features, including tumor histology and metastatic status.
  • To explore the prognostic significance of ERBB2 alterations on overall survival (OS) in breast cancer patients.

Main Methods:

  • Retrospective analysis of next-generation sequencing (DNA and RNA) data from 12,153 breast cancer samples.
  • Identification and classification of ERBB2 mutations, fusions, and copy number alterations.
  • Correlation of ERBB2 alterations with clinicopathologic features and HER2 status (including HER2-low).
  • Survival analysis using Kaplan-Meier estimates for patients with available outcome data.

Main Results:

  • Pathogenic ERBB2 mutations (ERBB2-mut) were found in 3.2% of tumors, with higher prevalence in liver metastases (5.7%) and lobular breast cancer (10%).
  • ERBB2 fusions were rare (0.3%). ERBB2-mut was more common in HER2-positive/low tumors compared to triple-negative breast cancer.
  • ERBB2-mut was significantly associated with coalterations in CDH1 (40.0%) and ERBB3 (10.6%) and correlated with worse overall survival.

Conclusions:

  • ERBB2 mutations and fusions occur across all breast cancer subtypes, notably in HER2+/low, metastatic, and lobular tumors.
  • The presence of ERBB2 mutations is associated with a poorer prognosis in breast cancer patients.
  • These findings highlight the clinical relevance of characterizing ERBB2 alterations for targeted therapy selection and prognostic assessment.

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