Proficiency assessment of HER-2 scoring in breast cancer
Over the last 20 years, pathological assessment of human epidermal growth factor receptor 2 (HER2) status has been essential in the selection of patients with breast cancer eligible for HER2-targeted therapies.43 To date, pathologists have focused on the identification of HER2-positive tumors defined as exhibiting either immunohistochemical (IHC) receptor protein overexpression (IHC score 3+ or IHC 2+ borderline score with HER2 gene amplification) based on the ASCO or College of American Pathologists (CAP) criteria.44 However, more recently, a new type of HER2-targeted therapy has been developed showing benefit in HER2-low breast carcinomas, with low level HER2 expression without HER2 gene amplification.45,46 Therefore, the question arises as to whether the current practice of HER2 testing allows the precise distinction of HER2-low categories that have to date been classified as HER2 negative.
In a global real-world laboratory study sponsored by Diaceutics, HER2 scoring proficiency was evaluated across 75 pathologists to determine the current ability to distinguish low levels of HER2 expression and identify challenges in HER2-low scoring in breast cancer. Digitized images of tissue sections were selected to cover a range of IHC scores with a focus on samples at the border between IHC 1+ and IHC 0 according to ASCO/CAP criteria. As part of the methodology, pathologists were also required to provide their own experience in HER2 staining and scoring methods through the Diaceutics DXRX platform.
The study found high levels of agreement among pathologists in the identification of the existing ASCO/CAP HER2 categories of negative versus positive, independent of training. However, after introducing the HER2-low category, a decrease in agreement rates was observed, with training only having a minor overall effect. This demonstrated a need for improved guidance on the classification of HER2-low cases. Leading authors of this article are to propose an improved HER2 IHC staining classification system with greater focus on these case types.