A Comparative Analysis of HER2 Immunohistochemistry in Core Biopsy Versus Excision in the Era of HER2 ``Low'' Breast Cancers.

[BACKGROUND] The Destiny B04 trial led to the recognition of HER2 low as a new entity defined as HER2 immunohistochemistry (IHC) score of 1 +/2 + and negative in situ hybridization (ISH) requiring detailed HER2 IHC scoring (negative = 0 & 1 +, equivocal = 2 +, and positive = 3 +). As per ASCO-CAP guidelines, biomarkers need not be repeated on excisions when done on core biopsy with some exceptions. The goal of our study was to compare the concordance of HER2 low between core biopsies and excisions and assess the need to repeat on excision.

[METHODS] At the study institution biomarkers are first performed on core biopsies and then repeated on all excisions in negative cases. We identified 301 cases of primary breast carcinomas with matched HER2 IHC on core biopsies and excisions. We reviewed and scored all HER2 IHC slides as per 2018 ASCO/CAP guidelines.

[RESULTS] The incidence of HER2 low on core biopsies decreased from 64% to 46% on excisions. The best concordance was seen in HER2 + (82%) and negative cases (84%), with most variability in predominantly 1 + and some 2 + cases in both directions. There was a greater loss (38%) than gain (16%) in HER2 low values from core biopsy to excision.

[CONCLUSIONS] HER2 low discordance in our series was predominantly due to loss from core biopsies to excisions, which maybe attributed to better meeting the pre analytic criteria on core biopsy. In contrast, the gain maybe due to intratumoral heterogeneity and or interobserver variability and despite low, worth repeating HER2 IHC on excisions in negative cases.