Circulating tumor DNA in breast cancer: From technological foundation to clinical implementation.

Circulating tumor DNA (ctDNA)-based liquid-biopsy has emerged as a transformative tool in breast cancer management, offering non-invasive, real-time insights across the clinical continuum. By capturing tumor-specific genetic and epigenetic alterations-such as mutations, copy number variations, and methylation patterns-ctDNA enables applications in early screening, evaluation of treatment response, minimal residual disease monitoring, and tracking of resistance mechanisms. Technological advances in PCR-based methods, next-generation sequencing, and biosensor-based profiling have significantly enhanced detection sensitivity and specificity, supporting personalized therapeutic guidance and dynamic adaptation of treatment strategies. However, clinical implementation faces challenges related to assay standardization, variable detection sensitivity, high costs, and limited large-scale prospective validation. Future efforts should focus on technological refinement, multi-omics integration, and evidence generation through large-scale multicenter clinical trials to position ctDNA as a cornerstone of precision oncology in breast cancer.