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Updated: Jun 17, 2026
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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
ERBB2/HER2 landscape and prognostic impact: large-scale, real-world analysis across solid cancers
A Shreenivas1, A Elliott2, T Corbiere3
1Department Oncology, Froedtert Hospital & Medical College of Wisconsin, Milwaukee, USA; City of Hope National Medical Center, Duarte, USA.
ESMO Open
|June 15, 2026
Summary
This study reveals complex links between ERBB2 genomic alterations and HER2 protein expression across diverse cancers. Understanding these relationships is crucial for personalized cancer treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Assessed human epidermal growth factor receptor 2 (HER2) protein expression via immunohistochemistry (IHC).
- Correlated HER2 protein expression with ERBB2 genomic alterations (amplifications and mutations).
- Utilized a large real-world patient database with molecular profiling data.
Purpose of the Study:
- To evaluate the frequency of HER2 protein expression and ERBB2 genomic alterations.
- To determine the prognostic impact of HER2 expression.
- To investigate the correlations between HER2 IHC and ERBB2 genomic alterations.
Main Methods:
- Analyzed over 200,000 tumors for ERBB2 copy number alterations and mutations using next-generation sequencing.
- Assessed HER2 IHC data (0, 1+, 2+, 3+) in over 88,000 samples.
- Evaluated whole transcriptome RNA and overall survival (OS) based on real-world insurance claims.
Main Results:
- ERBB2 amplifications/mutations found in a subset of cancers, often correlating with higher HER2 IHC.
- Significant associations between ERBB2 mutations and HER2 IHC positivity, even without amplifications.
- Median OS varied by HER2 IHC status (3+ highest), but survival benefits were mainly in breast and gastric cancers.
Conclusions:
- Complex relationships exist between ERBB2 alterations and HER2 IHC expression.
- Increased HER2 expression observed in tumors with mutations but without ERBB2 amplification.
- Cancer-specific variations in ERBB2/HER2 alterations necessitate individualized patient assessment.
