From detection to action: ctDNA-MRD surveillance and translational strategies in early breast cancer.
Recurrence remains a major cause of mortality in early breast cancer (EBC), and conventional follow-up often identifies relapse only after clinically detectable disease has emerged. Circulating tumor DNA-based minimal residual disease (ctDNA-MRD) testing offers the possibility of detecting molecular relapse earlier and refining recurrence-risk assessment during follow-up. This narrative review examines the evolving role of ctDNA-MRD in EBC, focusing on assay interpretation, longitudinal surveillance, MRD-guided trial design, and clinical implementation. Prospective studies consistently show that postoperative or surveillance ctDNA positivity is associated with an increased risk of recurrence. However, test performance and interpretation vary with assay characteristics and sampling strategies, and whether treatment initiated solely on the basis of MRD positivity can improve patient outcomes remains unresolved. The central challenge is no longer simply to detect residual disease earlier, but to determine when and how that information should influence care. Further prospective validation, assay standardization, clear pathways for uncertain findings, and patient-centered implementation will be needed before ctDNA-MRD can be integrated into routine management of EBC.