Abstract P3-02-10: Comparison of Circulating Tumour Cells in Peripheral and Central Venous Blood of Patients with Metastatic Breast Cancer: A Pilot Study
Authors: Peeters D , Van den Eynden G , Benoy I , Van der Auwera I , Trinh XB , Sas L , Van Laere S , van Dam P , Pauwels P , Peeters M , Vermeulen P , Dirix L. 
Published: April 2011

Background: Enumeration of circulating tumour cells (CTC), as performed by the CellSearch System (Veridex, Raritan, NJ, USA), has prognostic significance in patients with metastatic breast cancer (MBC). Questions remain on how these cells - if all - are capable to survive in the circulation and ultimately give rise to distant metastases. Experiments in mouse models have shown that CTC only appear transiently in the circulation after injection in the tail vein or left ventricle. Data on the discrete localisation of CTC in the blood stream and CTC kinetics in human breast cancer is still limited. The aim of this pilot study was to directly compare the amount of CTC measured in peripheral and central venous blood samples of patients with MBC in order to reveal possible differences. Methods: So far, we have included 18 patients with MBC presenting at our hospital with either primary metastatic (N=2) or progressive disease (N=16). Most patients suffered from diffuse metastatic involvement and were extensively pretreated. Clinically evident lung metastases were documented in 4/18 patients. Peripheral venous blood (PVB) - obtained from an antecubital vein - and central venous blood (CVB) samples - obtained from the subcutaneous port catheter - were drawn into CellSave Preservative tubes (Immunicon, Huntingdon Valley, PA) and processed in parallel using the CellSearch Circulating Tumor Cell Test (Veridex, Raritan, NJ, USA). With this test, CTC captured from 7.5 mL whole blood, are defined as EpCAM+, nuclear cells (DAPI+), expressing cytokeratins 8/18/19 and lacking CD45 expression.

Results: CTC were detected in both PVB and CVB samples of 16/18 patients. In 2 patients no CTC were detected, neither in PVB nor in CVB. In 16 patients with detectable CTC, the number of CTC was found to be significantly higher in CVB (median: 65; range: 3-4036) than in PVB (median: 45; range: 1-4013) samples (Wilcoxon Signed Ranks Test, P=0.001). When analyzing samples parewise, the number of CTC in CVB was higher than the number of CTC in PVB in 15/16 patients, although marginally in 4 of 15 patients (median ratio CVB/PVB: 1.8; range: 1.0-3.1). Only 1 patient showed a higher number of CTC in PVB (absolute value: 49 CTC/7.5 mL blood) as compared to CVB (absolute value: 41 CTC/7.5 mL blood).

Conclusions: In this study, a substantial decrease in the number of CTC was observed between CVB and PVB of patients with MBC. This difference might be relevant in the clinical setting as a quantitative cut off in the number of CTC is used to distinguish between patients with good and worse prognosis. As hand metastases are most uncommon, the lungs are suggested to function as the main sieve, even in the absence of clinically overt lung metastases. However, further research in larger patient populations and - where feasible - including radial arterial blood sampling, is required in order to confirm these results and to investigate human CTC kinetics in depth.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-10.