NPJ Breast Cancer. 2026 May 20. doi: 10.1038/s41523-026-00970-9. Online ahead of print.

ABSTRACT

Early detection of minimal residual disease (MRD) by liquid biopsy could enable earlier relapse identification in early-stage breast cancer (BC), but most approaches are single-analyte. We prospectively studied 58 patients with early-stage BC, including HR+/HER2-, triple-negative, and HER2+ subtypes, treated with neoadjuvant chemotherapy or primary surgery plus adjuvant therapy. Patient-specific droplet digital PCR assays were designed for both ctDNA and CTCs analysis, with one truncal tumour mutation tracked per patient for detection in both analytes, in serial high-volume blood samples collected at diagnosis before treatment, approximately 1 month after surgery, and at 6-month intervals during follow-up in patients at high risk of relapse. We developed a composite Liquid biopsy Minimal Residual Disease (L-MRD) score integrating six clinical and molecular variables. At baseline (pre-treatment), ctDNA and/or CTCs were detected in 67.2% of patients and remained positive post-surgery in 53.6%. During follow-up, MRD detection anticipated all relapses (100% sensitivity; median lead time 27.95 months) and the L-MRD score stratified 5-year recurrence risk (2.2% vs 41.6%; HR = 6.6; P = 0.04) with strong performance (AUC = 0.891; NPV = 97.8%). This dual-analyte, longitudinal MRD strategy improves relapse prediction and supports further research regarding the clinical utility of personalised surveillance in early-stage BC.

PMID:42161983 | DOI:10.1038/s41523-026-00970-9