A Decade of Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Breast Cancer in Spain: A Comprehensive Real-World Data Analysis (2013-2023)

BACKGROUND: Evaluating human epidermal growth factor receptor 2 (HER2) expression is essential for guiding targeted therapies in breast cancer (BC). In Spain, the CONFIRMA-HER2 registry is the main source of information on HER2 testing in BC. The aim of this analysis was to describe the HER2 status in BC and how it has evolved over the 10 years of the CONFIRMA-HER2 registry. MATERIALS AND METHODS: A retrospective observational study of HER2 testing (2013-2023) was conducted in BC samples from 160 Spanish hospitals, recorded in the CONFIRMA-HER2 registry. The analysis assessed rates and performance of immunohistochemistry (IHC) and in situ hybridization (ISH), as well as assessing changes in HER2 positivity over time. RESULTS: A total of 199,934 HER2 determinations recorded in the CONFIRMA HER2 registry were analyzed. IHC results showed 35.5% IHC 0, 27.8% IHC 1+, 22.7% IHC 2+, 11.2% IHC 3+, and 2.9% invalid/not evaluable. ISH was performed in 26.4% of cases, with 82.1% showing nonamplified HER2 gene status. Overall, 15.0% were HER2-positive, 83.2% HER2-negative, and 1.8% invalid/not assessable. Among HER2-negative cases, 54.9% were classified as HER2-low. Over time, HER2 positivity rates varied, likely reflecting changes in clinical practice influenced by updated guidelines. CONCLUSION: To our knowledge, this study is the first to compile and analyze the largest amount of real-world HER2 testing data in Spain. The CONFIRMA-HER2 registry is a key tool that provides comprehensive information on HER2 status as determined by IHC and ISH.