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Updated: Aug 28, 2025
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Selecting patients with HER2-low breast cancer: Getting out of the tangle
Ximena Baez-Navarro1, Roberto Salgado2, Carsten Denkert3
1Department of Pathology, Erasmus MC, Rotterdam, the Netherlands.
Abstract:
The promising effect of antibody-drug conjugates on breast cancer with low expression of HER2 (HER2-low) raises many questions regarding the optimal selection of patients for this treatment. A key question is whether HER2 immunohistochemistry, an assay optimised to detect HER2 amplification, is reliable enough to assess HER2 protein levels to select patients with HER2-low breast cancer in daily pathology practices worldwide. Moreover, whether this assessment can be performed with sufficient reproducibility between pathologists in daily practices is debatable. Herein, we address the historical track record of the CAP-ASCO HER2 Guidelines, the reported limited reproducibility by pathologists of HER2 immunohistochemistry in the non-amplified cases, and the performance variation of different antibodies. Based on this summary, we propose solutions to improve the robustness to enable reliable identification of patients with HER2-low breast cancer.
Insights
Selecting patients for HER2-low breast cancer treatment requires reliable HER2 testing. This study evaluates HER2 immunohistochemistry
Area of Science:
- Oncology
- Pathology
- Biomarker Detection
Background:
- Antibody-drug conjugates show promise for HER2-low breast cancer.
- Optimal patient selection for this therapy is crucial.
- HER2 immunohistochemistry (IHC) is commonly used but its reliability for HER2-low assessment is questioned.
Purpose of the Study:
- To evaluate the reliability and reproducibility of HER2 IHC for identifying HER2-low breast cancer patients.
- To address challenges in current HER2 testing for this specific patient group.
- To propose improvements for robust HER2-low patient identification.
Main Methods:
- Review of the CAP-ASCO HER2 Guidelines historical track record.
- Analysis of reported pathologist reproducibility issues in non-amplified HER2 cases.
- Assessment of performance variations among different HER2 antibodies.
Main Results:
- HER2 IHC, optimized for amplification detection, may not be sufficiently reliable for HER2-low assessment.
- Pathologist reproducibility in classifying HER2-low cases is a significant concern.
- Variability in antibody performance further complicates accurate assessment.
Conclusions:
- Current HER2 IHC methods require refinement for reliable HER2-low breast cancer patient selection.
- Standardization and improved protocols are needed to enhance reproducibility.
- Developing robust solutions is essential for effective targeted therapy in HER2-low breast cancer.
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