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Updated: May 13, 2026
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
Evaluation of HER2 in breast cancer: reality and expectations
Fernanda Milanezi1, Dina Leitão, Sara Ricardo
1Institute of Molecular Pathology and Immunology of Porto University, Rua Roberto Frias, s/n, 4200-465, Porto, Portugal +351 225570700 ; +351 225570799 ; mmilanezi@ipatimup.pt.
Background:
The introduction of drugs, whose mechanisms of action are directed against specific molecules involved in cancer initiation and/or progression, has changed the daily workup of breast cancer patients. At present, HER2 expression and/or amplification should be evaluated in every primary invasive breast cancer either at the time of diagnosis or at the time of recurrence, mostly to guide selection of trastuzumab in the adjuvant and/or metastatic setting. The adequate selection of patients is an essential step for indication of anti-HER2 therapy.
Objective:
This review focuses on the state of the art for HER2 evaluation in breast cancer, as well as expectations regarding future molecular assays based on mechanisms of resistance to HER2-driven therapy.
Methods:
Data were obtained by searching the PubMed database, including the terms 'HER2', 'in situ hybridisation', 'immunohistochemistry', 'trastuzumab', 'breast cancer', 'therapy', 'resistance' and 'tyrosine-kinase inhibitors', with a preference for updated publications.
Conclusion:
Pathologists have a central role in the selection of patients who will benefit from anti-HER-based therapies, with a responsibility to obtain the most reliable results for immunohistochemistry and in situ hybridisation techniques. Pre-analytical variables, such as type of fixative and time of fixation, are critical to guarantee consistent and quality assays, as well as to facilitate interpretation and decrease interobserver variability. Rigorous quality control and centralisation of techniques/interpretation of results are recommended to guarantee consistent assays.
Insights
Accurate HER2 (human epidermal growth factor receptor 2) testing is crucial for selecting breast cancer patients for anti-HER2 therapies like trastuzumab. Pathologists play a key role in ensuring reliable test results for effective treatment selection.
Area of Science:
- Oncology
- Molecular Diagnostics
- Pathology
Background:
- Targeted therapies have transformed breast cancer treatment.
- HER2 (human epidermal growth factor receptor 2) evaluation is essential for guiding anti-HER2 therapy selection.
- Accurate patient selection is critical for the efficacy of HER2-targeted treatments.
Purpose of the Study:
- To review the current state of HER2 evaluation in breast cancer.
- To discuss future molecular assays for HER2-driven therapy resistance.
- To highlight the role of pathologists in HER2 testing.
Main Methods:
- Literature search of the PubMed database.
- Inclusion of terms: HER2, in situ hybridisation, immunohistochemistry, trastuzumab, breast cancer, therapy, resistance, tyrosine-kinase inhibitors.
- Preference for recent publications.
Main Results:
- Pathologists are central to patient selection for anti-HER2 therapies.
- Immunohistochemistry and in situ hybridisation are key techniques.
- Pre-analytical variables (fixation) and quality control are critical for assay consistency and interpretation.
Conclusions:
- Reliable HER2 evaluation by pathologists is vital for anti-HER2 therapy.
- Standardized pre-analytical conditions and rigorous quality control are recommended.
- Centralization of techniques and interpretation can improve assay consistency and reduce variability.
