Mego Michal, Zuo Zhuang, Gao Hui, Cohen Evan N, Giordano Antonio, Tin Sanda, Anfossi Simone, Jackson Summer, Woodward Wendy, Ueno Naoto T, Valero Vicente, Alvarez Ricardo H, Hortobagyi Gabriel N, Khoury Joseph D, Cristofanilli Massimo, Reuben James M
Dr. J. M. Reuben, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA, Tel.: +1 713 745 6837, Fax: +1 713 794 1838, E-mail:
Thromb Haemost. 2015 Mar;113(3):593-8. doi: 10.1160/TH14-07-0597. Epub 2014 Nov 6.
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.
癌症是静脉血栓栓塞症(VTE)的一个风险因素。血浆D - 二聚体和纤维蛋白原水平升高也是VTE的风险因素。此外,在转移性乳腺癌(MBC)患者中,循环肿瘤细胞(CTC)的存在是VTE的一个风险因素。CTC与D - 二聚体之间的关系尚不清楚。本研究的目的是确定MBC患者中CTC是否与血浆D - 二聚体水平、纤维蛋白原水平及VTE风险相关。这项前瞻性研究纳入了2009年7月至2010年12月在MD安德森癌症中心接受治疗的47例MBC患者。使用CellSearch系统检测并计数外周血中的CTC。在检测CTC时测定血浆中的D - 二聚体和纤维蛋白原。33例患者(70%)有≥1个CTC,22例患者(47%)有≥5个CTC。有≥1个CTC或≥5个CTC的患者的平均血浆D - 二聚体水平(μg/mL)显著高于无CTC和<5个CTC的患者(分别为2.48和3.31 vs 0.80和0.84;截断值≥1个CTC时p = 0.006,截断值≥5个CTC时p = 0.003)。在多变量分析中,CTC的存在和转移灶数量与血浆D - 二聚体水平呈正相关。CTC与血浆纤维蛋白原水平无关。在中位随访13.5个月时,33例有≥1个CTC的患者中有3例(9%)发生VTE,而CTC检测不到的患者中无VTE发生。总之,MBC患者中CTC的存在与较高的血浆D - 二聚体水平相关。本研究进一步证实了CTC与VTE风险之间的关联。