Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements

Abstract

Circulating tumour DNA (ctDNA) is an emerging biomarker for monitoring cancers. The personalised disease monitoring in metastatic breast cancer (PDM-MBC) study is an ongoing study instigated to evaluate ctDNA as a biomarker to individualise imaging requirements in patients with MBC. Patients receiving first-line endocrine therapy (aromatase inhibitor + cyclin-dependent kinase 4/6 inhibitor) had plasma samples collected pre-treatment, weeks 2 and 4, and concurrently with imaging until progressive disease (PD). Here, we apply an experimental analytical workflow for ultrasensitive ctDNA analysis, utilising personalised ctDNA panels designed from mutations identified in tumour tissue, and present results for 24 patients. Twenty patients (83%) had detectable ctDNA pre-treatment. The median progression-free survival was 25.6 months, and 13 patients experienced PD, with rising ctDNA detected at or prior to PD in 12 patients (92%). If imaging had been omitted until the detection of rising ctDNA for at least one mutation, 68% (n = 71) of the scans performed amongst ctDNA-positive patients would have been avoided. Our results demonstrate that integration of personalised ctDNA monitoring of patients with MBC has potential to substantially reduce the imaging needs in patients showing ctDNA response to treatment.