Abstract
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. 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. 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. 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.
Highlights
Metastasis is the main cause of cancer-related death
The presence of circulating tumor cells (CTC) was significantly associated with shorter survival in the total population
The prognostic value of CTC was significant in both early (DFS: hazard ratio (HR), 2.86; 95% confidence intervals (CIs), 2.19–3.75; overall survival (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)
Summary
Metastasis is the main cause of cancer-related death. Even by currently available high-resolution imaging technologies, micrometastasis cannot be detected. In recent years much work has been entered into the detection and characterization of disseminated tumor cells (DTC) and circulating tumor cells (CTC). Through a pooled analysis accounting for 4,703 patients, Braun and colleagues [1] in 2005 reported that the presence of DTC in breast cancer patients is an independent predicator of poor prognosis. Authors' Affiliations: 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and 2Department of Tumor Biology, University Medical Center HamburgEppendorf, Hamburg, Germany. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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