Circulating tumor DNA in breast cancer in 2027: advancing liquid biopsy and molecular monitoring

PURPOSE OF REVIEW: Circulating tumor DNA (ctDNA) is increasingly used for molecular profiling in breast cancer, and its role as a longitudinal biomarker is expanding. This review examines recent evidence on serial ctDNA assessment, focusing on minimal residual disease (MRD) and molecular relapse in early breast cancer (EBC) and on molecular response and emerging resistance in metastatic breast cancer (MBC). RECENT FINDINGS: In EBC, ctDNA dynamics and MRD detection carry prognostic value, and serial surveillance can identify molecular relapse before overt recurrence. However, molecular lead time is not necessarily a therapeutic interception window, and the benefit of treating molecular relapse remains unproven. In MBC, serial ctDNA analysis can capture tumor dynamics, clonal evolution, and emerging resistance. Emerging cell-free DNA methylation-based approaches may enable molecular breast cancer subtyping, complementing genomic profiling. Definitions of molecular response and progression lack standardization across assays, metrics, thresholds, and sampling schedules. Nevertheless, randomized evidence shows that adapting treatment to selected actionable resistance alterations detected before radiological progression can improve clinical outcomes. SUMMARY: ctDNA monitoring is shifting liquid biopsy from a static molecular characterization toward the longitudinal assessment of disease evolution. Its future clinical value will depend on identifying molecular changes reliable and actionable enough to translate earlier detection into patient benefit.