Characteristics of HER2 FISH-Equivocal Breast Cancers and the Impacts on HER2 Status of 2018 ASCO/CAP Guideline

Abstract Background: According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with HER2 IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated.Methods: 195 HER2 FISH-equivocal breast cancers were collected between 2014 and 2018. The molecular subtype was determined according to 2013 St Gallen consensus, and HER2 status was also redefined following 2018 ASCO/CAP guideline. All cases were classified into 4 groups according to the average HER2 copy number (4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed. Results: 183 (93.8%) of 195 FISH-equivocal cases were of luminal subtype, while the other 12 (6.2%) were undetermined. Using 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized to HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) cases were treated with trastuzumab, but showed no difference in prognosis with patients who didn’t receive targeted therapy.Conclusions: In this study, all HER2 FISH-equivocal breast cancers were reclassified to be HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.