ERBB2
EstablishedHER2/ERBB2 overexpression drives aggressive breast cancer but also predicts response to targeted therapy.
HER2 is a protein that, when overactive, drives more aggressive breast cancer but also creates a target for very effective drugs. Recent discoveries mean even "low" levels of HER2 — once considered irrelevant — can now guide treatment, dramatically expanding who benefits from HER2-targeted therapy.
ERBB2 (HER2) is a transmembrane tyrosine kinase receptor in the EGFR family; its amplification or overexpression occurs in 15-20% of invasive breast cancers and drives a more aggressive tumor phenotype, making it one of the most important predictive biomarkers in oncology.
HER2 status determines eligibility for HER2-targeted therapies (trastuzumab and related drugs); historically classified as simply positive or negative, this framework has been substantially revised following the 2022 DESTINY-Breast04 trial, which showed major survival benefit from trastuzumab deruxtecan (T-DXd) in patients previously classified as "HER2-negative" but with low-level expression ("HER2-low").
CAP released a new biomarker-reporting template (effective March 2025) defining four discrete HER2-negative strata (0, 0+, 1+, 2+/ISH-negative) so pathologists can distinguish "HER2-ultralow" from true zero. A real limitation: roughly 20% of current HER2 testing may be inaccurate even with standardized IHC, a genuine caveat for any patient-facing content implying a clean yes/no result.
Following the DESTINY-Breast06 trial, the FDA expanded T-DXd approval in January 2025 to include hormone-receptor-positive, HER2-low/ultralow metastatic breast cancer, meaningfully broadening the population eligible for HER2-targeted therapy beyond the traditional HER2-positive definition.
The HER2-low/ultralow reclassification since 2022-2025 has significantly expanded eligible patient populations for targeted treatment.
- PMC. (2024). Standardized pathology report for HER2 testing in compliance with 2023 ASCO/CAP updates.
- ScienceDirect. (2025). International Expert Consensus Recommendations for HER2 Reporting in Breast Cancer.