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Thromb Haemost 2015; 113(03): 593-598
DOI: 10.1160/TH14-07-0597
Coagulation and Fibrinolysis
Schattauer GmbH

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

Michal Mego
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
6   Present affiliation: Department of Medical Oncology, Comenius University, School of Medicine, Bratislava, Slovakia
,
Zhuang Zuo
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Hui Gao
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Evan N. Cohen
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Antonio Giordano
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Sanda Tin
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Simone Anfossi
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Summer Jackson
2   Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Wendy Woodward
4   Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Naoto T. Ueno
2   Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
3   Stem Cell Transplantation and Cellular Therapy, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
5   Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Vicente Valero
2   Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
5   Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Ricardo H. Alvarez
2   Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
5   Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Gabriel N. Hortobagyi
2   Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Joseph D. Khoury
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
,
Massimo Cristofanilli
2   Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
7   Breast Center Thomas Jefferson University-Kimmel Cancer Center, Philadelphia, Pennsylvania, USA
,
James M. Reuben
1   Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
5   Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
› Author Affiliations Financial support: The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic is supported by a grant from the State of Texas Rare and Aggressive Breast Cancer Research Program. Michal Mego was supported by a UICC American Cancer Society International Fellowship for Beginning Investigators, ACSBI award ACS /08/006, and by grant 1/0724/11 funded by the Slovak Grant Agency VEGA. Massimo Cristofanilli, Wendy A. Woodward, and James M. Reuben are the recipients of National Institutes of Health R01 grant CA138239–02.
Further Information

Publication History

Received: 14 July 2014

Accepted after minor revision: 15 September 2014

Publication Date:
29 November 2017 (online)

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Summary

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 (g/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
 

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