Circulating tumor cells predict survival in early average-to-high risk breast cancer patients
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Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. / Rack, Brigitte; Schindlbeck, Christian; Jückstock, Julia; Andergassen, Ulrich; Hepp, Philip; Zwingers, Thomas; Friedl, Thomas W P; Lorenz, Ralf; Tesch, Hans; Fasching, Peter A; Fehm, Tanja; Schneeweiss, Andreas; Lichtenegger, Werner; Beckmann, Matthias W; Friese, Klaus; Pantel, Klaus; Janni, Wolfgang; SUCCESS Study Group.
in: JNCI-J NATL CANCER I, Jahrgang 106, Nr. 5, 01.05.2014.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Circulating tumor cells predict survival in early average-to-high risk breast cancer patients
AU - Rack, Brigitte
AU - Schindlbeck, Christian
AU - Jückstock, Julia
AU - Andergassen, Ulrich
AU - Hepp, Philip
AU - Zwingers, Thomas
AU - Friedl, Thomas W P
AU - Lorenz, Ralf
AU - Tesch, Hans
AU - Fasching, Peter A
AU - Fehm, Tanja
AU - Schneeweiss, Andreas
AU - Lichtenegger, Werner
AU - Beckmann, Matthias W
AU - Friese, Klaus
AU - Pantel, Klaus
AU - Janni, Wolfgang
AU - SUCCESS Study Group
N1 - © The Author 2014. Published by Oxford University Press.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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.
AB - 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.
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Breast Neoplasms
KW - Chemotherapy, Adjuvant
KW - Cyclophosphamide
KW - Deoxycytidine
KW - Epirubicin
KW - Female
KW - Fluorouracil
KW - Humans
KW - Immunomagnetic Separation
KW - Kaplan-Meier Estimate
KW - Lymphatic Metastasis
KW - Middle Aged
KW - Neoplasm Staging
KW - Neoplastic Cells, Circulating
KW - Prospective Studies
KW - Taxoids
U2 - 10.1093/jnci/dju066
DO - 10.1093/jnci/dju066
M3 - SCORING: Journal article
C2 - 24832787
VL - 106
JO - JNCI-J NATL CANCER I
JF - JNCI-J NATL CANCER I
SN - 0027-8874
IS - 5
ER -
