Circulating genomic landscape following cyclin-dependent kinase 4/6 inhibitors exposure in HR + /HER2- metastatic breast cancer: a retrospective multi-institutional Consortium analysis.

ABSTRACT: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) are the mainstay of treatment for hormone receptor positive, HER2 negative (HR + /HER2-) metastatic breast cancer (MBC). However, disease progression is inevitable and unveiling resistance mechanisms is crucial to guide post-CDK4/6i therapeutic strategies. In this study, we retrospectively analyzed a real-world, multi-institutional cohort of patients with HR + /HER2- MBC characterized by circulating tumor DNA (ctDNA) through next-generation sequencing (NGS) before starting second-line treatment. Among 93 patients previously treated with CDK4/6i, PIK3CA (37.6%), ESR1 (46.2%) and TP53 (31.2%) were the most altered genes. Comparing with a CDK4/6i plus ET naïve control cohort, ESR1 (p < 0.001) was significantly associ

SUBMITTER: Pontolillo L 

PROVIDER: S-EPMC12357851 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature