Use of Circulating Tumor DNA (ctDNA) for Early Molecular Detection of Breast Cancer Relapse in Patients with Triple-Negative Breast Cancer (TNBC)

Purpose of Review The intent of this review is to discuss the clinical utility of circulating tumor DNA (ctDNA) analysis for molecular residual disease (MRD) detection in patients with early-stage TNBC. Recent Findings Baseline ctDNA concentration correlates with tumor clinical features. ctDNA dynamics during neoadjuvant chemotherapy (NAC) predicts pathologic complete response (pCR), residual cancer burden (RCB), and relapse. Use of ctDNA plus imaging modalities during NAC may improve accuracy of pCR prediction. A lead-time exists from MRD detection and relapse. Tumor-informed assays tracking multiple ctDNA variants serially provide a more sensitive method for disease surveillance. Summary ctDNA, as a biomarker of MRD, identifies patients at risk for relapse and may complement conventional surveillance over the “wait and watch” approach. Further exploration is warranted to determine whether intervention in those with MRD positivity post NAC improves outcomes. Clinical trials using ctDNA assessments may inform approaches to tailor therapy selection in non-responders or de-escalate therapy for early responders. Standardization of protocols will be necessary.