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 <i>HER2</i>/CEP17 Ratio <2.0 and Average <i>HER2</i> Copy Number ≥4.0 and <6.0.

Abstract

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. To assess impact of the 2018 guideline on breast cancer with equivocal HER2 immunohistochemistry results. We retrospectively reviewed <i>HER2</i> fluorescence in situ hybridization (FISH) data (<i>HER2</i>/CEP17 ratio and average <i>HER2</i> 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 <i>HER2</i> FISH results according to 2013 and 2018 guidelines. A total of 1666 <i>HER2</i> FISH results from 1421 patients with equivocal HER2 immunohistochemistry were reviewed. Based on the 2013 guideline, <i>HER2</i> 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 <i>HER2</i>/CEP17 ratio lower than 2.0 and average <i>HER2</i> 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. The 2018 guideline eliminated <i>HER2</i> 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 <i>HER2</i> FISH-negative cases and a slight decrease in <i>HER2</i> FISH-positive cases.