Prognostic and monitoring value of circulating tumor DNA at multiple clinical time points in breast cancer.

Circulating tumor DNA (ctDNA) has emerged as a prognostic biomarker for breast cancer, potentially offering a more comprehensive representation of tumor genetic heterogeneity. In this study, we assessed the prognostic and monitoring values of ctDNA at multiple clinical time points during diagnosis and therapy. A total of 119 patients with breast cancer underwent ctDNA analysis using next-generation sequencing, targeting 47 breast cancer-related genes at three predefined time points (baseline, post-neoadjuvant chemotherapy [post-NAC], and follow-up). Disease-free survival (DFS) was analyzed based on ctDNA status. ctDNA was detected in 50.9% of patients at baseline, 25.0% post-NAC, and 58.3% during follow-up. ctDNA positivity was associated with worse DFS at baseline (hazard ratio [HR] 7.54, 95% CI: 1.71-33.17, P = 0.008), post-NAC (HR 3.54, 95% CI: 1.24-10.12, P = 0.018), and follow-up (HR 7.68, 95% CI: 0.98-59.97, P = 0.052). TP53 mutations were the most frequently observed, present in 37.5%, 14.8%, and 20.4% of patients at baseline, post-NAC, and follow-up, respectively. PIK3CA mutations were the second most common, detected in 11.6%, 4.5%, and 5.8% of patients, respectively. ctDNA positivity for these mutations consistently showed elevated HRs for disease progression across clinical time points (HR range, 2.73-20.49). ctDNA non-clearance was associated with the highest risk of disease progression (HR 81.09, P < 0.001) and remained the strongest independent prognostic factor in the multivariate analysis (HR 52.07, P < 0.001). ctDNA analysis provides significant clinical utility for prognostic stratification and disease monitoring in breast cancer management.