The Role of Cell-Free Circulating DNA in the Diagnosis and Prognosis of Breast Cancer

Cancer is the leading cause of death worldwide. Despite significant advances in cancer treatment, morbidity and mortality rates remain high. Tumor heterogeneity, particularly intertumoral heterogeneity, is a major cause of cancer therapy failure, underpinning tumor treatment problems and a variety of available therapeutic strategies, including molecularly targeted therapies. Recent advances in massively parallel sequencing and digital genomic techniques suggest that cell-free circulating tumor DNA (ctDNA) can be used as a “liquid biopsy.” In the case of breast cancer, ctDNA found in plasma can be used to non-invasively scan tumor genomes and assess tumor burden. ctDNA in plasma can be used to identify important genetic anomalies, track treatment responses, uncover drug resistance, and detect disease progression before clinical and radiographic confirmation. Furthermore, ctDNA can be used to identify tumor heterogeneity and metastasis-specific mutations, providing information to aid in patient treatment. We focused on the current state of cell-free ctDNA, including ctDNA biology, recently developed ctDNA detection techniques, and breast cancer-specific detection methods, with a focus on clinical applications of ctDNA-based biomarkers in breast oncology.