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Updated: Apr 29, 2026
Adaptation of Semiautomated Circulating Tumor Cell CTC Assays for Clinical and Preclinical Research Applications
Published on: February 28, 2014
Circulating tumor cells predict survival in early average-to-high risk breast cancer patients
Brigitte Rack1, Christian Schindlbeck2, Julia Jückstock2
1Affiliations of authors: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University Munich, Munich, Germany (BR, JJ, UA, KF); Department of Gynecology and Obstetrics, Clinical Center Traunstein, Traunstein, Germany (CS); Department of Gynecology and Obstetrics, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany (PH, TF); Augsburg, Germany (TZ); Braunschweig, Germany (RL); Frankfurt, Germany (HT); National Center for Tumor Diseases, University Hospital, Heidelberg, Germany (AS); Charité University Hospital Campus Virchow, Berlin, Germany (WL); Department of Obstetrics and Gynecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg, Erlangen, Germany (PAF, MWB); Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (KP); Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany (TWPF, WJ). brigitte.rack@med.uni-muenchen.de.
Background:
Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer.
Methods:
CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0-54). Kaplan-Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided.
Results:
Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30 mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) CONCLUSIONS: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.
