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.
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 cancerpatients. 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.
Authors: Mathias Gehrmann; Stefan Stangl; Gemma A Foulds; Rupert Oellinger; Stephanie Breuninger; Roland Rad; Alan G Pockley; Gabriele Multhoff Journal: PLoS One Date: 2014-08-28 Impact factor: 3.240