Abstract PO3-28-06: YAP1 expression is a good prognostic marker of hormone receptor-positive HER2-negative breast cancer: clinicopathologic analysis using the 21-gene recurrent score

Abstract Background: YAP1 is a downstream transcription factor of Hippo pathway and considered an oncogene in numerous solid cancers. Oncotype Dx (ODX) test is a multigene test for patients with hormone receptor-positive, HER2-negative (HR+HER2-) breast cancer that provides a risk score (RS), a high RS means high-risk. In this study, we investigated the relation between YAP1 expression and RS in patients with HR+HER2- breast cancer and validated the clinical impact of YAP1 on breast cancer using public datasets. Methods: This retrospective study included 401 patients who received curative-purpose resection of HR+HER2- breast cancer and underwent ODX test between May 2014 and April 2020 at Gangnam Severance Hospital in Seoul, Korea. YAP1 nuclear localization was evaluated using immunohistochemical staining, and clinicopathological parameters including RS were analyzed. Clinical outcome was validated using YAP1 mRNA expression in TCGA-BRCA and METABRIC datasets. Results: High-YAP1 expression was significantly correlated with low ODX RS (OR [odds ratio] 0.373, 95% CI [confidence interval] 0.198-0.703, p=0.002). High expression of YAP1 mRNA correlated with superior clinical outcomes, particularly in patients with ER-positive breast cancer (p < 0.0001, overall survival [OS] in METABRIC; p=0.00085, recurrent-free survival [RFS] in METABRIC; p=0.040, disease-free survival [DFS] in TCGA-BRCA). With different ESR1 mRNA expression thresholds and highly expressed YAP1, patients in the upper 80-, 60-, or 40 percentiles of ESR1 expression levels consistently demonstrated superior OS and RFS in METABRIC as well as DFS in TCGA-BRCA. Conclusion: YAP1 could serve as a prognostic marker as well as a therapeutic target in patients with HR+HER2- breast cancer. Citation Format: Inho Park, Yangkyu Lee, Jee Hung Kim, Soong June Bae, Sung Gwe Ahn, Joon Jeong, Yoon Jin Cha. YAP1 expression is a good prognostic marker of hormone receptor-positive HER2-negative breast cancer: clinicopathologic analysis using the 21-gene recurrent score [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-06.