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

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Abstract

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 EpCAMindependent 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 theCTCstatus 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 theCTCstatus assessed by the CellSearch system. In multivariate Cox proportionalhazards 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. © 2013 American Association for Clinical Chemistry.

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Ramirez, J. M., Fehm, T., Orsini, M., Cayrefourcq, L., Maudelonde, T., Pantel, K., & Alix-Panabières, C. (2014). Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients. Clinical Chemistry, 60(1), 214–221. https://doi.org/10.1373/clinchem.2013.215079

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