Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer.

Abstract

Background: Early-stage breast cancer (BC) diagnosis significantly reduces mortality, yet relapse remains a concern due to undetectable minimal residual disease (MRD). Liquid biopsies offer real-time insights into tumor dynamics, aiding MRD detection and therapy response evaluation. However, MRD detection is challenging due to low tumor DNA levels in circulation.

Methods: This prospective study included 20 HR + BC patients who had completed at least 5 years of adjuvant endocrine therapy (ET). Plasma samples were collected every 6 months over a median follow-up period of 2 years. Tumor-specific somatic variants identified through tumor tissue sequencing served as biomarkers for a patient-informed circulating tumor DNA (ctDNA) assay (CloneSight), which utilized a multiplex PCR-based next-generation sequencing (NGS) workflow.

Results: ctDNA was detected in patients who experienced clinical relapse, with positivity observed up to 68 months (5.7 years) prior to overt recurrence, highlighting its potential for early relapse identification. In non-relapsed patients, ctDNA remained undetectable in 93% of cases, reflecting a potential high level of specificity. The assay detected ctDNA in 50% of relapsed patients, while no ctDNA signal was identified in the majority of non-relapsed cases.

Conclusion: Our exploratory findings indicate that CloneSight could be a promising tool for MRD detection and relapse prediction, providing a cost-effective, patient-informed approach to ctDNA monitoring. The ability of this approach to detect relapse prior to clinical recurrence suggests its potential relevance in improving patient monitoring. These findings suggest that ctDNA-based MRD assays could play a role in future surveillance strategies for HR + BC, though further studies in larger cohorts are needed to confirm their clinical applicability.