Biological basis and clinical translation prospects of circulating cell‑free DNA in precision management of breast cancer (Review)

Circulating cell‑free DNA (cfDNA) has emerged as a valuable non‑invasive biomarker that provides unique insights into the spatial and temporal heterogeneity of tumors, serving a key role in cancer precision medicine. Applications of cfDNA include detecting disease progression before clinical and radiological confirmation, identifying actionable genomic alterations, monitoring treatment response, revealing mechanisms of treatment resistance and assessing prognosis. The latest progress in research on the biological characteristics of cfDNA has provided unprecedented molecular insights into cancer diagnosis and treatment, thereby markedly expanding its clinical application scope. The present review explored the latest findings in cfDNA biology and its applications in early diagnosis, treatment monitoring and prognostic assessment of breast cancer. The present review proposed a novel staged transformation strategy guided by the disease progression stage of breast cancer and the maturity of cfDNA technology. The present review aimed to systematically and efficiently promote the application of cfDNA in the full‑cycle management of breast cancer. Furthermore, the present review predicted cutting‑edge directions such as multi‑omics integration, artificial intelligence assistance and ethical considerations. Although cfDNA holds notable promise, its clinical translation is still limited by low‑abundance signals in early‑stage tumors, insufficient detection standardization and the complexity of bioinformatics interpretation. The present review was based on the integration of existing evidence; however, majority of studies are still retrospective or small‑sample prospective, indicating a need to elevate the evidence level. Future research should focus on developing ultra‑high‑sensitivity multi‑omics technology, establishing an international standardization system and verifying the actual effectiveness of cfDNA in guiding clinical decisions through large‑scale prospective clinical trials. The ultimate goal is to realize the comprehensive application of cfDNA in early screening and personalized treatment of breast cancer.