Assessing endocrine resistance: monitoring circulating ESR1 mutations in Irosustat-treated ER positive breast cancer.

ABSTRACT:

Purpose

We aimed to investigate the prevalence and spectrum of ESR1 mutations alongside cell-free DNA (cfDNA) dynamics in patients with estrogen receptor-positive metastatic breast cancer recruited to the phase II IRIS study who had progressed on first-line aromatase inhibitor (AI) therapy and then continued their AI in combination with Irusostat (40 mg), an irreversible steroid sulfatase inhibitor.

Methods

cfDNA was isolated from 96 serial plasma samples from 24 patients, alongside primary tumour DNA (n = 16), and analysed by next-generation sequencing using a custom-designed mutation panel on the Illumina NovaSeq platform.

Results

Thirteen of 16 tumour DNA samples harboured at least one somatic mutation across nine genes. Twenty one of the 24 patients (88%) had at l

SUBMITTER: Page K 

PROVIDER: S-EPMC12689781 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature