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Clinical Trial
. 2014 May 15;106(5):dju066.
doi: 10.1093/jnci/dju066.

Circulating Tumor Cells Predict Survival in Early Average-To-High Risk Breast Cancer Patients

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Free PMC article
Clinical Trial

Circulating Tumor Cells Predict Survival in Early Average-To-High Risk Breast Cancer Patients

Brigitte Rack et al. J Natl Cancer Inst. .
Free PMC article

Erratum in

  • J Natl Cancer Inst. 2014 Sep;106(9):doi/10.1093/jnci/dju273

Abstract

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.

Figures

Figure 1.
Figure 1.
Kaplan–Meier analysis according to the presence or absence (neg.) of peripheral blood circulating tumor cells (CTCs) before chemotherapy (CT). A) Disease-free survival. B) Overall survival. C) Distant disease-free survival. D) Breast cancer–specific survival. Two-sided log-rank test.
Figure 1.
Figure 1.
Kaplan–Meier analysis according to the presence or absence (neg.) of peripheral blood circulating tumor cells (CTCs) before chemotherapy (CT). A) Disease-free survival. B) Overall survival. C) Distant disease-free survival. D) Breast cancer–specific survival. Two-sided log-rank test.
Figure 1.
Figure 1.
Kaplan–Meier analysis according to the presence or absence (neg.) of peripheral blood circulating tumor cells (CTCs) before chemotherapy (CT). A) Disease-free survival. B) Overall survival. C) Distant disease-free survival. D) Breast cancer–specific survival. Two-sided log-rank test.
Figure 1.
Figure 1.
Kaplan–Meier analysis according to the presence or absence (neg.) of peripheral blood circulating tumor cells (CTCs) before chemotherapy (CT). A) Disease-free survival. B) Overall survival. C) Distant disease-free survival. D) Breast cancer–specific survival. Two-sided log-rank test.
Figure 2.
Figure 2.
Kaplan–Meier analysis according to the presence or absence of five or more peripheral blood circulating tumor cells (CTCs) before chemotherapy (CT). A) Disease-free survival. B) Overall survival. Two-sided log-rank test.
Figure 3.
Figure 3.
The correlation of hazard ratios with increasing numbers of circulating tumor cells (CTCs) per 30mL of blood according to survival endpoints.
Figure 4.
Figure 4.
Kaplan–Meier analysis for disease-free survival according to the presence (+) or absence (−) of peripheral blood circulating tumor cells (CTCs) before and after chemotherapy (CT). Two-sided log-rank test.

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