Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients

TY - JOUR

T1 - Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients

AU - Ramirez, Jean-Marie

AU - Fehm, Tanja

AU - Orsini, Mattea

AU - Cayrefourcq, Laure

AU - Maudelonde, Thierry

AU - Pantel, Klaus

AU - Alix-Panabières, Catherine

PY - 2014/1/1

Y1 - 2014/1/1

N2 - BACKGROUND: Detection of circulating tumor cells (CTC) in breast cancer patients is currently performed in many clinical trials, using different technologies, in particular the EpCAM-dependent CellSearch® system. The purpose of this study was to investigate the incidence and prognostic relevance of viable CTC in a large cohort of metastatic breast cancer (MBC) patients.METHODS: A total of 254 MBC patients were enrolled in a prospective multicenter study at first diagnosis of metastatic disease or disease progression (before the start of a new treatment regimen). After EpCAM-independent enrichment, viable CTC releasing cytokeratin-19 as an epithelial cell marker were detected in the peripheral blood by an EPISPOT assay, and the Food and Drug Administration cleared CellSearch was used as the reference method.RESULTS: Using the EPISPOT assay, CTC were detected in 59% of MBC patients. The overall survival (OS) was linked with the CTC status measured by EPISPOT (P = 0.0191), which allowed stratification of MBC patients in low- and high-risk groups. This stratification could be improved by addition of the CTC status assessed by the CellSearch system. In multivariate Cox proportional-hazards regression analysis, the 3 methods used to determine the level of CTC (EPISPOT, CellSearch, and combination of EPISPOT/CellSearch) were compared by the Bayesian information criterion method. Interestingly, the combination of the EPISPOT and CellSearch assays was the strongest predictor of OS (hazard ratio, 22.6; 95% CI, 2.8-184.08).CONCLUSIONS: This is the first study in which CTC detection using the EPISPOT assay was evaluated on a large cohort of MBC patients, showing prognostic relevance of the presence of viable CTC.

AB - BACKGROUND: Detection of circulating tumor cells (CTC) in breast cancer patients is currently performed in many clinical trials, using different technologies, in particular the EpCAM-dependent CellSearch® system. The purpose of this study was to investigate the incidence and prognostic relevance of viable CTC in a large cohort of metastatic breast cancer (MBC) patients.METHODS: A total of 254 MBC patients were enrolled in a prospective multicenter study at first diagnosis of metastatic disease or disease progression (before the start of a new treatment regimen). After EpCAM-independent enrichment, viable CTC releasing cytokeratin-19 as an epithelial cell marker were detected in the peripheral blood by an EPISPOT assay, and the Food and Drug Administration cleared CellSearch was used as the reference method.RESULTS: Using the EPISPOT assay, CTC were detected in 59% of MBC patients. The overall survival (OS) was linked with the CTC status measured by EPISPOT (P = 0.0191), which allowed stratification of MBC patients in low- and high-risk groups. This stratification could be improved by addition of the CTC status assessed by the CellSearch system. In multivariate Cox proportional-hazards regression analysis, the 3 methods used to determine the level of CTC (EPISPOT, CellSearch, and combination of EPISPOT/CellSearch) were compared by the Bayesian information criterion method. Interestingly, the combination of the EPISPOT and CellSearch assays was the strongest predictor of OS (hazard ratio, 22.6; 95% CI, 2.8-184.08).CONCLUSIONS: This is the first study in which CTC detection using the EPISPOT assay was evaluated on a large cohort of MBC patients, showing prognostic relevance of the presence of viable CTC.

KW - Aged

KW - Breast Neoplasms

KW - Clinical Chemistry Tests

KW - Female

KW - Humans

KW - Middle Aged

KW - Multivariate Analysis

KW - Neoplasm Metastasis

KW - Neoplastic Cells, Circulating

KW - Prognosis

KW - Reference Standards

KW - Tumor Markers, Biological

U2 - 10.1373/clinchem.2013.215079

DO - 10.1373/clinchem.2013.215079

M3 - SCORING: Journal article

C2 - 24255082

VL - 60

SP - 214

EP - 221

JO - CLIN CHEM

JF - CLIN CHEM

SN - 0009-9147

IS - 1

ER -