Human epidermal growth factor receptor 2 (HER2) status in breast cancer: practice points and challenges

Human epidermal growth factor receptor 2 (HER2)‐enriched breast cancer benefits significantly from anti‐HER2 targeted therapies. This highlights the critical need for precise HER2 immunohistochemistry (IHC) interpretation serving as a triage tool for selecting patients for anti‐HER2 regimens. Recently, the emerging eligibility of patients with HER2‐low breast cancers for a novel HER2‐targeted antibody–drug conjugate (T‐DXd) adds challenges to HER2 IHC scoring interpretation, notably in the 0–1+ range, which shows high interobserver and interlaboratory staining platform variability. In this review, we navigate evolving challenges and suggest practical recommendations for HER2 IHC interpretation. This review navigates challenges in HER2 immunohistochemical evaluation: pre‐analytical aspects, specimen selection and interobserver and interantibody variability, and proposes practical recommendations for pathologists in optimising HER2 IHC interpretation.