Abstract
PurposeTo evaluate the relationship between circulating tumor cells (CTCs) and standard coagulation tests in both a discovery and a validation cohort of patients with advanced breast cancer.MethodsIn a retrospective (n = 77) and a prospective (n = 92) study of patients with progressive advanced breast cancer, CTC count, platelet number, fibrinogen level, D-dimers, prothrombin time, and activated partial thromboplastin time were measured. The association between these coagulation studies and CTC count was analyzed. The impact of these measurements on overall survival (OS) was assessed.ResultsIn both cohorts, results were similar; absolute CTC count was significantly associated to D-dimer level and inversely with platelet count. In the prospective cohort, quantification of tumor-derived extracellular vesicles (tdEVs) was associated with CTC count, and with coagulation abnormalities (low platelet count and increased D-dimers). tdEVs did not add to CTC count in predicting changes in platelets or D-dimers. In multivariate analysis only CTC ≥ 5 CTC/7.5 mL, ER status, HER2 status and lines of chemotherapy were associated with OS. In patients with terminally metastatic breast cancer, very high CTC counts are prevalent.ConclusionA significant association exists between increasing CTC number and increased D-dimers and decreased platelet counts, suggesting a potential role for CTCs as a direct contributor of intravascular coagulation activation. In patients with advanced and progressive breast cancer, abnormalities in routine coagulation tests is the rule. In patients with terminally advanced breast cancer a “leukemic” phase with high CTC count is prevalent.
Highlights
Coagulation activation is detectable in plasma in the majority of patients with localized and/or advanced breast cancer [1,2,3,4]
Presence of visceral disease, number of lines of chemotherapy (0 vs 1 vs 2+), ln circulating tumor cells (CTCs), CTC at baseline, CTC ≥ 5, the ln D-dimers, platelet count and serum LDH were significantly associated with overall survival
In two cohorts of patients with stage IV breast cancer, and excluding patients with established prior or current TE events and those patients on drugs interfering with normal coagulation, the prevalence of coagulation abnormalities, was respectively 91% and 85% for the retrospective and the prospective cohort
Summary
Coagulation activation is detectable in plasma in the majority of patients with localized and/or advanced breast cancer [1,2,3,4]. We have previously demonstrated that venous effluent levels of plasma D-dimers in patients with localized colorectal cancer are significantly increased in comparison with arterial levels [20]. This suggests a substantial contribution of local intratumoral coagulation activation to the changes as measured in blood, suggestive of an overflow phenomenon. The first cohort consists of patients that have participated in prior trials on CTCs in MBC and for whom, for whatever reason, coagulation tests were performed. We consider this first data set as a discovery cohort. The second cohort consists of patients with MBC that participated in the P1133 prospective study on different quantification methods for CTC enumeration
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