New treatment options for metastatic HER2-low breast cancer : Consequences for histopathological diagnosis
Carsten Denkert1, Annette Lebeau2,3, Hans Ulrich Schildhaus4,5
1Institute of für Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Baldingerstr. 1, 35043, Marburg, Germany. carsten.denkert@uni-marburg.de.
Abstract:
The overexpression of HER2 in breast cancer is a classic example for molecular targeted therapy, and it has been shown that classical anti-HER2 therapeutics were only effective in patients with HER2 overexpressing tumors. Therefore, in recent decades, pathologists have been focused on the reliable identification of HER2 overexpressing tumors. Based on the results of recent clinical trials in metastatic breast cancer with antibody-drug conjugates (ADCs), this diagnostic strategy for evaluation of HER2 is currently changing. It has been shown that the ADC trastuzumab-deruxtecan is effective not only against tumors with classical HER2 overexpression, but also against HER2-low tumors. These clinical trial results lead to a paradigm shift in the treatment of patients whose tumours were previously classified as HER2 negative. In addition to the identification of HER2 (score 3+) overexpressing tumors, it is necessary to identify HER2-low expressing tumors (defined as an immunohistochemistry (IHC) score of 1+ or IHC2+ with negative in situ hybridization).Due to the therapeutic consequences, it is important to quickly adapt the diagnostic workup and reporting to the new requirements. In addition, the new therapeutic options for anti-HER2 therapy lead to new challenges for standardization as well as to new scientific questions for the characterization of tumors with low HER2 expression.
Insights
The human epidermal growth factor receptor 2 (HER2) diagnostic strategy is shifting. New antibody-drug conjugates (ADCs) show efficacy in HER2-low breast cancers, expanding treatment options beyond HER2-overexpressing tumors.
Area of Science:
- Oncology
- Pathology
- Pharmacology
Background:
- HER2 overexpression is a hallmark for targeted therapy in breast cancer.
- Traditional anti-HER2 therapies are effective only in HER2-overexpressing tumors.
- Pathology diagnostics have focused on identifying HER2 overexpression (3+).
Purpose of the Study:
- To highlight the evolving diagnostic strategy for HER2 evaluation in breast cancer.
- To discuss the impact of new antibody-drug conjugates (ADCs) on HER2-negative classifications.
- To emphasize the need for identifying HER2-low expressing tumors.
Main Methods:
- Review of recent clinical trials involving antibody-drug conjugates (ADCs) in metastatic breast cancer.
- Analysis of diagnostic criteria for HER2 evaluation, including immunohistochemistry (IHC) and in situ hybridization (ISH).
- Discussion of the implications of new therapeutic findings on pathological workup.
Main Results:
- Trastuzumab-deruxtecan demonstrates efficacy in both HER2-overexpressing and HER2-low breast tumors.
- This finding necessitates a reclassification of tumors previously considered HER2-negative.
- HER2-low tumors are defined as IHC 1+ or IHC 2+ with negative ISH.
Conclusions:
- The diagnostic approach for HER2 in breast cancer requires adaptation to include HER2-low status.
- New therapeutic options for HER2-low breast cancer present challenges for diagnostic standardization.
- Further research is needed to characterize tumors with low HER2 expression.
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