Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.
Institut Curie, Unit of Biometry, PSL Research University, INSERM U900, Paris, France.
J Thromb Haemost. 2017 Oct;15(10):1981-1988. doi: 10.1111/jth.13792. Epub 2017 Sep 1.
Essentials Tumor cells circulating in blood (CTC) may favor thrombotic events in cancer patients. We assessed the impact of CTC on the risk of thrombosis in metastatic breast cancer. Baseline CTC detection was the only independent factor associated with the risk of thrombosis. CTC detection under therapy may be the hidden link between tumor progression & thrombosis.
Background Circulating tumor cell (CTC) count is a major prognostic factor in metastatic breast cancer (MBC) and has been reported to be associated with thrombosis in short-term studies on MBC patients. Objective To assess whether CTC detection (CellSearch ) before first-line chemotherapy impacts the risk of thrombosis throughout the course of MBC. Patients/Methods Among patients included before first-line chemotherapy for MBC in the prospective IC2006-04 CTC detection study (NCT00898014), the electronic medical files of those patients treated at Institut Curie (Paris, France) were searched in silico and manually checked for incident venous or arterial thrombotic events (TE) in the course of MBC. Univariate and multivariate analyses were performed using Cox and Fine-Gray models, adjusted for age and Khorana score. Results/Conclusions With a median follow-up of 64 months (25-81 months), among the 142 patients included, 34 (24%) experienced a TE (incidence rate, 8 TE/100 patient-years). The TE incidence rate was 13 TE/100 patient-years for the 80 patients with ≥ 1 CTC/7.5 mL of blood before initiating first-line chemotherapy, vs. only 4 TE/100 patient-years for the 62 CTC-negative patients. Fine-Gray multivariate analysis (with death as competing event) included age, Khorana score and baseline lactate dehydrogenase and CTC levels: detectable CTC was the only factor significantly associated with an increased risk of TE (sub-distribution hazard ratio [SHR] for patients with [1-4] CTC = 3.1, 95% CI [1.1; 8.6], SHR for patients with ≥ 5 CTC = 1.4, 95% CI [0.5; 4.6]). This study shows that CTC detection before starting first-line chemotherapy is an independent risk factor for TE in MBC patients.
评估转移性乳腺癌(MBC)患者一线化疗前循环肿瘤细胞(CTC)检测是否会影响整个 MBC 过程中血栓形成的风险。
在 IC2006-04 CTC 检测研究(NCT00898014)中,对纳入的 MBC 患者进行前瞻性研究,在接受一线化疗前对患者进行 CTC 检测(CellSearch),对接受 Institut Curie(巴黎,法国)治疗的患者的电子病历进行了电子病历检索,并手动检查了 MBC 期间静脉或动脉血栓事件(TE)的发生情况。采用 Cox 和 Fine-Gray 模型进行单变量和多变量分析,调整年龄和 Khorana 评分。
在中位随访 64 个月(25-81 个月)的 142 例患者中,有 34 例(24%)发生了 TE(发生率为 8 TE/100 患者-年)。在开始一线化疗前,80 例≥1 CTC/7.5ml 血液的患者中有 13 例 TE/100 患者-年,而 62 例 CTC 阴性患者中有 4 例 TE/100 患者-年。多变量 Fine-Gray 分析(以死亡为竞争事件)包括年龄、Khorana 评分和基线乳酸脱氢酶和 CTC 水平:可检测的 CTC 是唯一与 TE 风险增加显著相关的因素([1-4] CTC 患者的亚分布危险比 [SHR] = 3.1,95%CI [1.1;8.6],≥5 CTC 患者的 SHR = 1.4,95%CI [0.5;4.6])。
本研究表明,MBC 患者一线化疗前 CTC 检测是 TE 的独立危险因素。