Circulating tumor DNA in breast cancer: updates from SABCS 2025.

Circulating tumor DNA (ctDNA) has emerged as a transformative biomarker in breast cancer, enabling sensitive assessment of tumor burden, molecular residual disease, and treatment resistance. Data presented at the 2025 San Antonio Breast Cancer Symposium (SABCS) demonstrate that ctDNA has moved beyond prognostication to guide treatment in advanced hormone receptor positive disease, most notably in the phase III SERENA-6 trial, where ctDNA-detected ESR1 mutations prospectively triggered endocrine therapy switch and significantly improved clinical outcomes. In early-stage breast cancer, converging evidence across subtypes shows that ctDNA-defined minimal residual disease (MRD) robustly identifies patients at high risk of recurrence. Collectively, these findings position ctDNA as a potential biomarker for dynamic treatment adaptation, supporting the next phase of precision oncology focused on MRD-guided escalation, de-escalation, and therapeutic interception across the breast cancer continuum.