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

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.