Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTCs) in the peripheral blood of patients with metastatic breast cancer, less evidence is available for the prognostic relevance of CTCs at the time of primary diagnosis.
PATIENTS AND METHODS
We conducted a pooled analysis of individual data from 3,173 patients with non-metastatic (Stage I-III) breast cancer from 5 breast cancer institutions. The prevalence and numbers of CTCs were assessed at the time of primary diagnosis with the United States Food and Drug Administration-cleared CellSearch® System (Janssen Diagnostics, LLC). Patient outcomes were analyzed using meta-analytic procedures, univariate log-rank tests, and multivariate Cox proportional hazard regression analyses. The median follow-up duration was 62.8 months.
One or more CTCs were detected in 20.2% of the patients. CTC-positive patients had larger tumors, increased lymph node involvement, and a higher histological tumor grade than did CTC-negative patients (all P < 0.002). Multivariate Cox regressions, which included tumor size, nodal status, histological tumor grade, and hormone-receptor and HER2 status, confirmed that the presence of CTCs was an independent prognostic factor for disease-free survival (hazard ratio (HR), 1.82; 95% confidence interval (CI), 1.47 to 2.26), distant disease-free survival (HR, 1.89; 95% CI, 1.49 to 2.40), breast cancer-specific survival (HR, 2.04; 95% CI, 1.52 to 2.75), and overall survival (HR, 1.97; 95% CI, 1.51 to 2.59).
In patients with primary breast cancer, the presence of CTC was an independent predictor of poor disease-free, overall, breast-cancer-specific, and distant disease-free survival.