Circulating tumour cells are linked to plasma D-dimer levels in patients with metastatic breast cancer

Thromb Haemost. 2015 Mar;113(3):593-8. doi: 10.1160/TH14-07-0597. Epub 2014 Nov 6.

Abstract

Cancer is a risk factor for venous thromboembolism (VTE). Elevated plasma D-dimer and fibrinogen levels are also risk factors for VTE. Furthermore, in patients with metastatic breast cancer (MBC), the presence of circulating tumour cells (CTCs) is a risk factor for VTE. The relationship between CTCs and D-dimer is unknown. The aim of this study was to determine whether CTCs correlate with plasma D-dimer level, fibrinogen level, and risk of VTE in MBC. This prospective study included 47 MBC patients treated from July 2009 through December 2010 at the MD Anderson Cancer Center. CTCs in peripheral blood were detected and enumerated using the CellSearch system. D-dimer and fibrinogen were measured in plasma at the time of CTC detection. Thirty-three patients (70 %) had ≥ 1 CTC, and 22 patients (47 %) had ≥ 5 CTCs. Patients with ≥ 1 CTC or ≥ 5 CTCs had significantly higher mean plasma D-dimer levels (µg/mL) than patients with no CTCs and < 5 CTCs (2.48 and 3.31 vs 0.80 and 0.84, respectively; p=0.006 for cut-off ≥ 1 CTC and p=0.003 for cut-off ≥ 5 CTCs). In multivariate analysis, presence of CTCs and number of metastases were positively associated with plasma D-dimer level. CTCs were not associated with plasma fibrinogen level. At median follow-up of 13.5 months, three of 33 patients (9 %) with ≥ 1 CTC had VTE, vs no patients with undetectable CTCs. In conclusion, the presence of CTCs was associated with higher levels of plasma D-dimer in MBC patients. This study further confirms an association between CTCs and risk of VTE.

Keywords: Circulating tumour cells; D-dimer; fibrinogen; metastatic breast cancer; venous thromboembolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Breast Neoplasms / blood*
  • Breast Neoplasms / complications
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / blood*
  • Carcinoma, Ductal, Breast / complications
  • Carcinoma, Ductal, Breast / secondary*
  • Chi-Square Distribution
  • Disease-Free Survival
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplastic Cells, Circulating / pathology*
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Texas
  • Up-Regulation
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / etiology*
  • Venous Thromboembolism / pathology

Substances

  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D