Impact of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Updates on HER2 Assessment in Breast Cancer With Equivocal HER2 Immunohistochemistry Results With Focus on Cases With HER2/CEP17 Ratio <2.0 and Average HER2 Copy Number ≥4.0 and <6.0

Abstract

Context.— The American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline in breast cancer was updated in 2018 to address issues on interpretation of uncommon results using dual-probe in situ hybridization according to the 2013 guideline. Objective.— To assess impact of the 2018 guideline on breast cancer with equivocal HER2 immunohistochemistry results. Design.— We retrospectively reviewed HER2 fluorescence in situ hybridization (FISH) data (HER2/CEP17 ratio and average HER2 copy number per cell) of HER2 immunohistochemistry–equivocal (2+ or 1+ to 2+) breast cancers at our center between January 2014 and May 2018 and compared HER2 FISH results according to 2013 and 2018 guidelines. Results.— A total of 1666 HER2 FISH results from 1421 patients with equivocal HER2 immunohistochemistry were reviewed. Based on the 2013 guideline, HER2 FISH results were amplified in 346 cases (20.8%), equivocal in 242 (14.5%), and nonamplified in 1078 (64.7%). Using the 2018 guideline, 258 cases (16%) were reclassified, including 242 previously equivocal test results (15%) and 16 previously positive results (1%) reclassified as negative. The subset of 2013 HER2-equivocal and 2018 HER2-nonamplified cases with HER2/CEP17 ratio lower than 2.0 and average HER2 copy number 4.0 or higher and lower than 6.0 showed higher incidence of micropapillary morphology compared with HER2-amplified cases. Despite most patients in this group not receiving HER2-targeted treatment, 96% had no evidence of disease at follow-up. Conclusions.— The 2018 guideline eliminated HER2 FISH–equivocal cases by reclassifying HER2-equivocal cases and cases with nonclassical amplification without HER2 overexpression as HER2 negative. As a consequence, we observed a considerable increase in HER2 FISH–negative cases and a slight decrease in HER2 FISH–positive cases.