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Updated: Jul 18, 2025
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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
172
HER2-low expression in patients with advanced or metastatic solid tumors
B Uzunparmak1, C Haymaker2, G Raso2
1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Summary
Human epidermal growth factor receptor 2 (HER2)-low is common in many solid tumors. This finding suggests that HER2-targeted therapies may benefit a broad range of patients with HER2-low cancers.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biomarkers
Background:
- Human epidermal growth factor receptor 2 (HER2)-low is a newly defined cancer subtype.
- HER2-low status is characterized by HER2 1+ or 2+ expression via immunohistochemistry (IHC) without HER2 gene amplification by in situ hybridization (ISH).
- Limited data exists on HER2-low prevalence across diverse tumor types and its stability between primary and metastatic sites.
Purpose of the Study:
- To investigate the frequency of HER2-low expression across various solid tumors.
- To assess the concordance of HER2 expression between primary and metastatic cancer samples.
- To correlate HER2 expression with ERBB2 genomic alterations.
Main Methods:
- HER2 expression was evaluated using IHC in 4701 patients with solid tumors.
- Paired primary and metastatic samples from breast and gastric/gastroesophageal junction (GEJ) cancers were analyzed for HER2 expression (IHC) and amplification (ISH).
- ERBB2 genomic alterations were assessed by next-generation sequencing (NGS) in non-breast, non-gastric/GEJ tumors.
Main Results:
- HER2 expression was observed in 49.8% of all cancers studied.
- HER2-low expression (IHC 1-2+) was prevalent across multiple tumor types, including breast (47.1%), gastric/GEJ (34.6%), salivary gland (50.0%), lung (46.9%), endometrial (46.5%), urothelial (46%), and gallbladder (45.5%) cancers.
- High concordance for HER2 3+ expression was noted between primary and metastatic breast cancer samples (kappa=0.85).
- ERBB2 alterations were found in 7.5% of patients with non-breast, non-gastric/GEJ tumors undergoing NGS; however, 35.7% of patients without detected ERBB2 alterations still showed some level of HER2 expression by IHC.
Conclusions:
- HER2-low expression is a frequent finding across a wide spectrum of solid tumors.
- The consistent HER2 expression in paired primary and metastatic samples supports its reliability as a biomarker.
- These findings indicate that a significant population of patients with HER2-low solid tumors may be candidates for HER2-targeted therapies.
