Abstract PS2-10-20: Dual biomarker approach for minimal residual disease detection in early breast cancer using high-volume blood samples

Abstract Background: Early detection of minimal residual disease (MRD) through liquid biopsy may enable timely identification of relapse in early-stage breast cancer (BC), yet most strategies rely on single-analyte approaches. Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) reflect distinct aspects of tumour biology, but their combined utility for MRD detection remains poorly characterised. Patients and methods: We conducted a prospective study of 58 early BC patients treated with either neoadjuvant chemotherapy or primary surgery followed by adjuvant therapy. Patient-specific droplet digital PCR assays targeting tumour-derived mutations were used to analyse ctDNA and CTCs in serial high-volume blood samples collected at baseline, after surgery, and throughout follow-up. A composite score (L-MRD) integrating six clinical and molecular variables was developed to stratify relapse risk. Results: At baseline, ctDNA and/or CTCs were detectable in 67.2% of patients, with higher detection rates in the neoadjuvant cohort. Combined biomarker positivity persisted in 53.6% of cases post-surgery. MRD detection during follow-up anticipated all clinical relapses, achieving 100% sensitivity and a median lead time up to 34.60 months. The L-MRD score stratified patients into low- and intermediate/high-risk groups with 5-year recurrence rates of 2.2% versus 41.6%, respectively (HR=6.6; P=0.04). Prognostic discrimination remained significant for distant relapse and demonstrated strong predictive performance (AUC=0.891; NPV=97.8%). Conclusions: This dual-biomarker approach enables ultra-sensitive and early MRD detection. Integration of longitudinal ctDNA and CTCs data into a composite score improves risk stratification and may inform personalised surveillance strategies in early BC. Citation Format: I. Comino-Méndez, J. Pascual, J. Velasco-Suelto, M. Quirós-Ortega, A. Godoy-Ortiz, M. Álvarez, E. Alba. Dual biomarker approach for minimal residual disease detection in early breast cancer using high-volume blood samples [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-10-20.