ESR1 Y537S and D538G Mutations Drive Resistance to CDK4/6 Inhibitors in Estrogen Receptor-Positive Breast Cancer.

ABSTRACT:

Purpose

Breast cancers with ESR1 mutations are resistant to antiestrogen therapy. In this study, we aimed to investigate the association of ESR1 mutations with resistance to CDK4/6 inhibitors (CDK4/6i) using real-world data analysis and experimental validation.

Experimental design

A total of 3,958 patients with estrogen receptor-positive metastatic breast cancer with DNA sequencing data were analyzed. Breast tumor DNA and ctDNA were sequenced using the Tempus xT tumor assay and Tempus xF liquid biopsy, respectively. Patients were stratified into either treated with CDK4/6i (tumor tissue: 1,070; ctDNA: 1,885) or CDK4/6i naïve (tumor tissue: 750; ctDNA: 253). Engineered MCF7 cells carrying ESR1Y537S or ESR1D538G knock-in mutations were used to study antitumor efficacy of the C

SUBMITTER: Lin CA 

PROVIDER: S-EPMC12045714 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature