ERBB2/HER2 Expression in a Real-World Oncology Cohort: A Retrospective Observational Study

Abstract Background: HER2, encoded by the ERBB2 gene, is an important predictive biomarker in breast cancer and other solid tumors. HER2 assessment by immunohistochemistry (IHC), in situ hybridization (ISH), and molecular testing guides therapeutic decisions. The increasing use of antibody-drug conjugates has also increased the importance of accurately identifying lower levels of HER2 expression.¹ Methods: We retrospectively analyzed an institutional ERBB2/HER2 testing dataset containing 552 test records from 518 unique patients. The study was conducted over a period of 5 years and 2 months, from July 2021 to August 2026. Testing included IHC, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Demographic characteristics, tumor type, HER2 IHC status, and ERBB2 molecular findings were evaluated. Results: IHC was the most frequently used testing method, accounting for 444 (80.4%) records, followed by NGS in 96 (17.4%) and FISH in 12 (2.2%). Breast cancer was the predominant diagnosis, comprising 341 (61.8%) records. Among 333 breast cancer IHC records, 176 (52.9%) were IHC 0, 21 (6.3%) IHC 1+, 25 (7.5%) IHC 2+, and 111 (33.3%) IHC 3+. The mean age was similar between IHC 3+ and IHC 0–2+ groups (56.3 vs 56.4 years; p=0.967). No significant association was observed between IHC 3+ status and tumor stage (p=0.678). ERBB2 alterations were detected in 5 of 96 NGS records (5.2%). Conclusion: This real-world cohort demonstrates substantial heterogeneity in HER2 expression. Approximately one-third of breast cancer IHC records showed strong HER2 expression, while lower expression categories were also observed. NGS identified ERBB2 alterations in a subset of tested tumors. Accurate HER2 assessment and standardized reporting remain important for biomarker-directed treatment.