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

SIMPLE SUMMARY: YAP1, a downstream transcription factor of the Hippo pathway, is regarded as an oncogene in various solid tumors. This study explores the relationship between YAP1 expression and the risk score from the Oncotype Dx test in patients with hormone-receptor-positive, HER2-negative (HR+HER2−) breast cancer. In a retrospective review of 401 patients using YAP1 nuclear localization via immunohistochemical staining and clinicopathologic analysis, high-YAP1 expression significantly correlated with a lower risk score. In a public dataset analysis, elevated YAP1 mRNA expression was associated with better clinical outcomes, particularly in ER-positive patients. In summary, YAP1 could serve as a prognostic marker as well as potential therapeutic target in HR+HER2− breast cancer patients. ABSTRACT: 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.