Differences of HER2 Status by HercepTest and PATHWAY 4B5 Immunohistochemical Assays in Breast Cancer

BACKGROUND/AIM: Human epidermal growth factor receptor 2 (HER2) status assessment is subdivided according to trastuzumab-deruxtecan (T-DXd) suitability, and there is a discrepancy in HER2 staining depending on reagents. This study investigated HER2 status by HercepTest and PATHWAY 4B5 immunohistochemical assays in breast cancer. PATIENTS AND METHODS: We reviewed the HER2 test data for breast cancer from the institutional pathology database between January 2020 and December 2024. The HercepTest was used in the early period (January 2020 to April 2023), and 4B5 was used in the late period (May 2023 to December 2024). The HER2 status of 2,328 breast cancer tissues (2,313 fresh and 15 archived tissues) was analyzed. RESULTS: The HER2 statuses by HercepTest and 4B5 in fresh samples were as follows: positive 9.5% and 8.6%, low 59.5% and 48.5%, ultralow 18.2% and 21.8%, and zero 12.9% and 21.1%, respectively. Eight (53.3%) archived samples from the same cases had changed HER2 status (1 upgraded and 7 downgraded). CONCLUSION: HER2 staining was lower in 4B5 testing than in the HercepTest. Companion diagnosis using 4B5 is required to determine indications for T-DXd, especially for HER2-ultralow evaluations.