Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients

BackgroundCirculating tumor cells (CTCs) can be identified in approximately 25% of nonmetastatic breast cancer patients, and data are emerging regarding their prognostic significance. We hypothesized that CTCs identified before resection of the primary tumor would predict worse outcomes in nonmetastatic breast cancer patients.Study DesignWe performed CTC enumerations on 509 patients with nonmetastatic breast cancer as part of an IRB-approved study. The CTCs (per 7.5 mL blood) were identified using the CellSearch System (Janssen). The presence of ≥1 CTC meeting morphologic criteria for malignancy was considered a positive result. Log-rank test and Cox regression analysis were applied to establish the association of CTCs with relapse-free and overall survival.ResultsMedian follow-up was 48 months and mean age was 53 years. Fifty-nine percent of patients (299 of 509) had tumors larger than 2 cm, and 46% (234 of 509) had positive lymph nodes. One hundred sixty-six patients received neoadjuvant chemotherapy (NACT) before CTC assessment, and 343 patients were chemonaïve. One or more CTC was identified in 43 of 166 (26%) NACT treated patients, and in 81 of 343 (24%) chemonaïve patients. Circulating tumor cells were not associated with tumor size, grade, or lymph node status (p = NS). Detection of 1 or more CTCs predicted decreased relapse-free (log-rank p < 0.001, hazard ratio [HR] 2.72, 95% CI 1.57 to 4.72; p < 0.001) and overall survival (log-rank p = 0.02, HR 2.29, 95% CI 1.12 to 4.67; p = 0.03) at 48 months of follow-up.ConclusionsOne or more CTCs identified before resection of the primary breast tumor predicted worse relapse-free and overall survival, irrespective of primary tumor size, grade, or lymph node positivity.