HER2 gene amplification testing by fluorescence in situ hybridization (FISH): Comparison of the ASCO-CAP guidelines with FISH scores used for enrollment in breast cancer international research group (BCIRG) clinical trials.

515Background: ASCO-CAP recently recommended further changes to evaluation of HER2 gene amplification by FISH. We retrospectively assessed the impact of the guidelines using annotated BCIRG-005, BCIRG-006, and BCIRG-007 clinical trial data for which we have detailed outcomes. Methods: HER2 FISH status of BCIRG-005/006/007 breast cancers was re-evaluated according to 2013/2014 ASCO-CAP guidelines, which designate five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell; group 1 (“ISH-positive”): HER2-to-CEP17 ratio ≥2.0, average HER2 copies ≥4.0; group2 (“ISH-positive”): ratio ≥2.0, copies<4.0; group3 (“ISH-positive”): ratio<2.0, copies ≥6.0; group 4 (“ISH-equivocal”): ratio<2.0, copies ≥4.0 and <6.0; and group 5 (“ISH-negative”): ratio<2.0, copies<4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio). Results: Among 10,468 breast cancers successfully e...