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Assessing the impact of the 2018 American Society of Clinical Oncology/College of American Pathologists recommendations on human epidermal growth factor receptor 2 testing by fluorescence in situ hybridization in breast carcinoma

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Abstract

The American Society of Clinical Oncology/College of American Pathologists recently updated their recommendations on human epidermal growth factor receptor 2 (HER2) testing by fluorescence in situ hybridization (FISH) in invasive breast cancer, with a focus on the clarification of less common test patterns of ISH. We assessed the impact of the updated ASCO/CAP guidelines on 1044 FISH tested tumors by comparing categorization according to the 2007, 2013, and 2018 ISH classification criteria. The 2013 guidelines increased the number of positive cases (17.4% vs 10.7%) identifying 70 (6.7%) additional patients who met the eligibility criteria for consideration for HER2-targeted therapy compared with the 2007 guidelines. There was a reduction in equivocal tumors (7.7%) with tumors classified as equivocal by the 2007 guidelines (n = 136) redistributed into positive (74, 54.4%) and negative (49, 36.0%) groups. The 2018 guidelines reclassified 10.8% of tumors in our series with a reduction in the number of positive tumors (7.1%). While the proportion of positive tumors (10.2%) was similar to that in 2007 (10.7%), the composition of this group was significantly altered. HER2 equivocal cases, a group which under the 2013 guidelines caused diagnostic and treatment difficulties, were largely eliminated. Our findings suggest that the 2018 update represents a potentially significant change in therapeutic options for a substantial proportion of patients with 2.9% of FISH-positive tumors according to the 2007 and 2013 guidelines now categorized as HER2 negative and, thus, ineligible for HER2-targeted therapy.

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Authors and Affiliations

  1. Department of Histopathology, St. Vincent’s University Hospital, Dublin, Ireland

    Ciara Murray, Louise Flanagan, Claire D’Arcy & Cecily M. Quinn

  2. Department of Medical Oncology, St. Vincent’s University Hospital, Dublin, Ireland

    Giuseppe Gullo

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  1. Ciara Murray
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  2. Louise Flanagan
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  3. Claire D’Arcy
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  4. Giuseppe Gullo
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  5. Cecily M. Quinn
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Contributions

CMQ conceived and designed the study. CM and CMQ researched and analyzed data. CM, LF, and CMQ wrote, edited, and reviewed the manuscript. CD, GG, and CMQ edited and reviewed the manuscript. All authors gave final approval for publication. CM and CMQ take full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

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Correspondence to Ciara Murray.

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Murray, C., Flanagan, L., D’Arcy, C. et al. Assessing the impact of the 2018 American Society of Clinical Oncology/College of American Pathologists recommendations on human epidermal growth factor receptor 2 testing by fluorescence in situ hybridization in breast carcinoma. Virchows Arch 476, 367–372 (2020). https://doi.org/10.1007/s00428-019-02636-3

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  • DOI: https://doi.org/10.1007/s00428-019-02636-3

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