Tumor genomics and response to CDK 4/6 inhibitors for patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC).

1046Background: The combination of endocrine therapy with a cyclin-dependent kinase (CDK) 4/6 inhibitor, such as palbociclib, has changed the treatment paradigm of HR+ MBC, particularly as 1stline therapy. However, there are no predictive biomarkers at present, and little is known about the impact of tumor genomics on outcomes. For example, mutations in TP53 could impact the ability of p53 to negatively regulate p21, thereby promoting cell cycle progression despite CDK 4/6 inhibition. The aim of this study was to evaluate the association between tumor genomics, particularly PIK3CA and TP53 mutations, and response to CDK 4/6 inhibitors in HR+ MBC. Methods: All HR+/HER2- MBC patients at our institution receiving a CDK 4/6 inhibitor in the second line or beyond were identified. Tumor genomics were analyzed utilizing the institutional tumor genotyping next generation sequencing (NGS) assay known as “Snapshot-NGS assay” on DNA isolated from the tumor, covering key oncogenic driver mutations and tumor suppresso...