Meta-Analysis of the Prognostic Value of Circulating Tumor Cells in Breast Cancer

Purpose: The prognostic value of circulating tumor cells (CTC) detected in breast cancer patients is currently under debate. Different time points of blood collections and various CTC assays have been used in the past decades. Here, we conducted the first comprehensive meta-analysis of published literature on the prognostic relevance of CTC, including patients with early and advanced disease. Experimental Design: A comprehensive search for articles published between January 1990 and January 2012 was conducted; reviews of each study were conducted and data were extracted. The main outcomes analyzed were overall survival (OS) and disease-free survival (DFS) in early-stage breast cancer patients, as well as progression-free survival (PFS) and OS in metastatic breast cancer patients. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also conducted. Results: Forty-nine eligible studies enrolling 6,825 patients were identified. The presence of CTC was significantly associated with shorter survival in the total population. The prognostic value of CTC was significant in both early (DFS: HR, 2.86; 95% CI, 2.19-3.75; OS: HR, 2.78; 95% CI, 2.22-3.48) and metastatic breast cancer (PFS: HR, 1.78; 95% CI, 1.52-2.09; OS: HR, 2.33; 95% CI, 2.09-2.60). Further subgroup analyses showed that our results were stable irrespective of the CTC detection method and time point of blood withdrawal. Conclusion: Our present meta-analysis indicates that the detection of CTC is a stable prognosticator in patients with early-stage and metastatic breast cancer. Further studies are required to explore the clinical utility of CTC in breast cancer. Clin Cancer Res; 18(20); 5701-10. (C) 2012 AACR.