Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer.

We investigated frequencies of HER2-low breast cancer (BC) (immunohistochemistry [IHC] 1+ or 2+ without gene amplification) before and after IHC conditions were modified in order to understand the impact of IHC staining conditions on frequencies of HER2-low BC. Primary BC cases diagnosed at the Yeungnam University Hospital (YUH, n = 728) or Keimyung University Dongsan Hospital (KUDH, n = 290) in 2022 were reviewed, and data on HER2 status and IHC conditions were collected (cohort 1). Both institutions used the 4B5 antibody for HER2 IHC but had different staining protocols. After modifications of the IHC conditions at both institutions, primary BC cases (YUH, n = 324 and KUDH, n = 135) diagnosed from April to July 2023 (cohort 2) were reviewed to assess any changes in the frequency of HER2 status. In cohort 1, of the 728 cases diagnosed at YUH, 556 (76.4%) were HER2-zero, 76 (10.4%) were HER2-low, and 96 (13.2%) were HER2-positive, and of the 290 cases diagnosed at KUDH, 135 (46.6%) were HER2-zero, 82 (28.3%) were HER2-low, and 73 (25.2%) were HER2-positive. Modifications in HER2 IHC staining conditions dramatically increased the frequencies of HER2-low BC in cohort 2 (YUH 38.9% and KUDH 49.6%), but they did not result in significant changes in the HER2-positive rates (YUH 15.4% and KUDH 25.2%) compared to cohort 1. In conclusion, minor modifications in HER2 IHC staining conditions significantly affected the frequency of HER2-low BC but had little impact on the HER2-positivity rate. Each pathology laboratory should verify IHC conditions using control slides (including 1+) to enable the accurate identification of HER2-low BC.