Circulating Tumor Cells in Early Breast Cancer: A 10-Year Follow-Up Update

Background: Circulating tumor cells (CTCs) are a rare population of cells considered the seeds of metastasis, detectable in the bloodstream of patients with solid tumors. In breast cancer (BC) their prognostic value is established in the metastatic setting but remains uncertain in early-stage disease. This study provides a 10-year follow-up analysis of disease-free survival (DFS) in a previously described cohort of early-stage BC patients, aiming to evaluate the long-term prognostic significance of CTC detection. Methods: As reported in a previous study, 48 patients with stage I-II operable BC were enrolled. CTCs were isolated from peripheral blood using an EpCAM-independent enrichment method followed by DEPArray analysis at baseline (pre-surgery) and six months post-surgery. CTC positivity was defined as the presence of ≥1 CTC. DFS outcomes were assessed over a 10-year follow-up period, and statistical analyses were performed using Kaplan-Meier survival estimates and log-rank tests. Results: After 10 years, 3 patients (6.3%) experienced disease relapse, and 2 developed lymphomas. No statistically significant association was observed between CTC presence-either pre-surgery (p = 0.13) or post-surgery (p = 0.25)-and DFS. Overall, the detection of CTCs using this method did not reliably predict long-term outcomes in this cohort. Conclusions: CTC enumeration before and after surgery does not appear to be a reliable prognostic marker for long-term DFS in early-stage BC. Although associated with specific pathological features such as vascular invasion, the role of CTC analysis in this setting remains limited by methodological challenges and cost. Larger, standardized studies are needed to validate the prognostic relevance of conventional and non-conventional CTC populations in early BC.