Dynamic ctDNA-MRD in breast cancer: subtype-specific implications for perioperative decision-making, postoperative surveillance, and MRD-guided therapy

Circulating tumor DNA-based molecular residual disease (ctDNA-MRD) provides prognostic information in early breast cancer, but its detection performance and clinical interpretation differ across molecular subtypes. This review examines subtype-specific ctDNA clearance, molecular re-emergence, and implications for neoadjuvant response assessment, postoperative surveillance, and MRD-directed trials. In ER-positive/HER2-negative disease, low shedding and late recurrence limit the negative predictive value of a single negative result, while the clinical utility of extended monitoring remains unproven. In HER2-positive disease, rapid clearance during neoadjuvant therapy may complement pathological complete response and residual cancer burden but does not independently determine adjuvant treatment. In triple-negative breast cancer, higher detectability and early recurrence strengthen the association between persistent or re-emergent ctDNA and short-term relapse risk. Across subtypes, ctDNA-MRD should complement clinicopathological and imaging assessment rather than independently guide treatment. Standardized assays and randomized intervention trials are required before routine clinical implementation.