Concordance between pathologists and between specimen types in detection of HER2-low breast carcinoma by immunohistochemistry

Recent clinical trials indicate that HER2-targeted therapy may benefit HER2-low breast cancer patients including HER2 score 1+ or 2+ and no gene amplification. Concordance between pathologists and between core biopsy and surgical excision in establishing HER2-low status was evaluated. 57 patients with HER2 negative breast cancer (IHC 0, 1+, or 2+, no gene amplification) by core biopsy were included. Core biopsy and representative tumor from corresponding surgical excision was immunostained for HER2. Original HER2 IHC scores were interpreted using 2018 guidelines. Three pathologists independently interpreted again under 2023 guidelines. Kappa statistic evaluated agreement of HER2 IHC scores. Applying 2013 guidelines, HER2 IHC scores were concordant between study pathologists in 46 of 57 (81 %) core biopsy and 50 of 57 (88 %) surgical resections. Kappa statistics were 0.78 and 0.85 (substantial agreement), for inter-pathologist agreement of core biopsy and surgical resections under 2013 guidelines; 0.55 (moderate agreement) for agreement between first interpretation by 2018 guidelines and second interpretation by 2023 guidelines; and 0.13 (slight agreement) for agreement in HER2 consensus scores between outside core and surgical resection and 0.49 (moderate agreement) for inside core and surgical resection. Low HER2 expression was found in 28 of 57 (49 %) core biopsy and in 25 of 57 (44 %) surgical excisions. Interobserver agreement among study pathologists was good in core biopsy and surgical excisions, applying updated 2023 guidelines. Intratumoral heterogeneity in protein expression and preanalytical factors may result in variable identification of HER2-low status in core biopsy and surgical excision specimens.