Circulating Tumor DNA in Metastatic Breast Cancer: Current Clinical Applications and Future Directions

Abstract Purpose of Review This review aims to examine the current evidence around the use of circulating tumor DNA (ctDNA) in metastatic breast cancer (MBC), including ongoing clinical trials and future directions for integrating ctDNA into clinical practice. Recent Findings ctDNA provides an opportunity to meaningfully advance the field of precision oncology and personalize care for patients with MBC. There are now several targeted therapeutic agents approved for the treatment of MBC that are paired with ctDNA-based companion diagnostic assays for identifying actionable genomic alterations. Beyond treatment selection, growing evidence supports the prognostic value of baseline ctDNA and on-treatment ctDNA dynamics for predicting treatment response and survival. Novel clinical trials are assessing the clinical utility of serial ctDNA monitoring to detect early molecular progression and acquired resistance mutations before radiographic progression and whether this approach improves long-term outcomes and quality of life. Using ctDNA to guide treatment escalation and de-intensification decisions is being tested in ongoing trials. The use of ctDNA is also being explored in settings of clinical unmet need including CNS disease and lobular breast cancer. Summary In recent years, ctDNA has emerged as a valuable biomarker in the treatment of MBC by enabling minimally invasive, real-time assessment of tumor genomics and disease biology. While its role in genomic profiling and treatment selection is established, and its prognostic value in tracking disease response is strong, ongoing prospective studies are needed to determine how ctDNA should be used in routine clinical practice for metastatic breast cancer.