Current perspectives on circulating tumor DNA in breast cancer: a narrative review.

Abstract

Background and objective: In recent years, research and development of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) as cancer biomarkers for use in diagnosis, prognosis, and monitoring of therapeutic responses have progressed. ctDNA has become an important focus for biomarker analysis in breast cancer and in current clinical trials. This review aims to discuss the current status and future prospects of ctDNA in breast cancer.

Methods: We provide a Narrative Review about ctDNA in breast cancer. We used PubMed to search for reports of ctDNA in breast cancer. We also searched the clinicaltrials.gov database and the Cochrane Library for clinical trials involving ctDNA analysis in breast cancer and other cancer types up to November 30, 2025 (reviewed November 30, 2025). We reviewed all articles written in English, including clinical trials, meta-analyses, and prospective and retrospective studies.

Key content and findings: The uses of ctDNA in breast cancer can currently be broadly classified into the following categories: (I) cancer screening; (II) prediction of treatment response in the neoadjuvant setting; (III) monitoring of minimal residual disease; (IV) assessment of the genomic landscape for treatment selection; and (V) monitoring clonal evolution. Clinical trials are underway to assess ctDNA-guided therapy and interventions for ctDNA-positive cases with poor prognosis, especially in the perioperative period. ctDNA is present at low concentrations in the blood in early-stage breast cancer, and a highly sensitive method is needed to detect ctDNA. The U.S. Food and Drug Administration has developed draft guidance regarding the use of ctDNA in therapeutic development.

Conclusions: ctDNA has become important as a source of biomarkers in clinical trials, and its clinical and research significance is expected to increase.