Blood-based monitoring identifies acquired and targetable driver HER2 mutations in endocrine-resistant metastatic breast cancer.

ABSTRACT: Plasma genotyping identifies potentially actionable mutations at variable mutant allele frequencies, often admixed with multiple subclonal variants, highlighting the need for their clinical and functional validation. We prospectively monitored plasma genotypes in 143 women with endocrine-resistant metastatic breast cancer (MBC), identifying multiple novel mutations including HER2 mutations (8.4%), albeit at different frequencies highlighting clinical heterogeneity. To evaluate functional significance, we established ex vivo culture from circulating tumor cells (CTCs) from a patient with HER2-mutant MBC, which revealed resistance to multiple targeted therapies including endocrine and CDK 4/6 inhibitors, but high sensitivity to neratinib (IC50: 0.018 μM). Immunoblotting analysi

SUBMITTER: Medford AJ 

PROVIDER: S-EPMC6635494 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature