YAP1 Expression in HR+HER2-Breast Cancer: 21-Gene Recurrence Score Analysis and Public Dataset Validation

Background: YAP1, an oncogene in numerous cancers, is a downstream transcription factor of the Hippo pathway. This study focuses on its relationship with the Oncotype Dx (ODX) test risk score (RS) in patients with hormone-receptor-positive, HER2-negative (HR+HER2-) breast cancer. Methods: We retrospectively analyzed 401 HR+HER2- breast cancer patients from Gangnam Severance Hospital who underwent ODX tests (May 2014-April 2020). YAP1 nuclear localization was evaluated via immunohistochemical staining and its clinical correlation with clinicopathological parameters, including RS, was analyzed. Public datasets TCGA-BRCA and METABRIC validated clinical outcomes. Results: YAP1 expression negatively correlated with ODX RS (OR 0.373, p = 0.002). Elevated YAP1 mRNA levels corresponded to better clinical outcomes, specifically in ER-positive patients, with significant results in METABRIC and TCGA-BRCA datasets (p < 0.0001 OS in METABRIC, p = 0.00085 RFS in METABRIC, p = 0.040 DFS in TCGA-BRCA). In subsets with varying ESR1 mRNA expression and pronounced YAP1 expression, superior survival outcomes were consistently observed. Conclusion: YAP1 may be a valuable prognostic marker and potential therapeutic target in HR+HER2- breast cancer patients.