Impact of the 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing of invasive breast carcinoma: a focus on tumours assessed as 'equivocal' for HER2 gene amplification by fluorescence in-situ hybridization

Aims: The updated 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines include changes to HER2 in-situ hybridization (ISH) interpretation criteria. We conducted a retrospective review of a consecutive cohort of primary breast carcinomas to assess the impact of updated guidelines on HER2 classification and laboratory resource utilization, and to characterize the pathobiology of HER2 equivocal tumours. Methods and results: A total of 904 dual-probe HER2/chromosome enumeration probe (CEP17) FISH tests on invasive breast carcinomas were studied. Eighty-five (9.4%) cases had a classification change with the updated guidelines; 66 (7.3%) went from HER2-negative to -equivocal, 15 cases (1.7%) were reclassified as HER2-positive and four cases from HER2-equivocal to negative. A subset of primary breast cancers, reported initially as HER2-negative but -equivocal by 2013 guidelines, was identified. Traditional pathological factors of this subset were compared to HER2-negative and -positive control cases. The three HER2 groups demonstrated statistically significant differences with respect to prognostic factors, including tumour size, grade and nodal involvement. Conclusions: The updated HER2 testing guidelines will result in the reclassification of approximately 9.4% of primary breast cancers with uncertainty regarding the clinical impact of this reclassification in the majority of cases. Resource utilization will increase as a result of the recommendation for retesting.