Reevaluating HER2-null breast cancer using an enhanced HER2 immunohistochemistry protocol

Human epidermal growth factor receptor 2 (HER2) status is crucial for the classification of breast cancer and the selection of its treatment. Although HER2-low breast cancer is a recognized therapeutic subgroup, the classification of HER2 immunohistochemistry (IHC) 0 remains unclear. We reassessed 58 HER2-null breast cancer cases using an enhanced HER2 IHC protocol and the VENTANA OptiView detection system. HER2 expression was evaluated based on membrane positivity rate (%) and staining intensity. Microscopic assessment was performed to determine the percentage of HER2-positive tumor cells. Digital image analysis was used to quantify staining intensity. Detectable membrane HER2 positivity was observed in all tumors previously classified as HER2-null; the positivity rates ranged from 0.33% to 90% and the staining intensity indicated both inter- and intratumoral heterogeneity. These findings suggest that enhanced HER2 IHC protocols can improve detection sensitivity. This approach may help to refine HER2 classification and optimize patient selection for HER2-targeted therapies. Further research is needed to determine the clinical significance of HER2 expression detected using enhanced protocols.