Coagulation/fibrinolysis and circulating tumor cells in patients with advanced breast cancer

Purpose To 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. Methods In a retrospective ( n = 77) and a prospective ( n = 92) study of patients with progressive advanc...

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Published in:	Breast cancer research and treatment Vol. 192; no. 3; pp. 583 - 591
Main Authors:	Dirix, Luc Y., Oeyen, Steffi, Buys, Andy, Liégois, Vincent, Prové, Annemie, Van De Mooter, Tom, Van Laere, Steven, Vermeulen, Peter B.
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-04-2022 Springer Springer Nature B.V
Subjects:	Analysis Biomarkers, Tumor Blood Blood coagulation factors Breast cancer Breast Neoplasms - pathology Cancer Cancer research Care and treatment Chemotherapy Clinical Trial Coagulation ErbB-2 protein Extracellular vesicles Female Fibrin Fibrinogen Fibrinolysis Humans Leukemia Medical examination Medical research Medicine Medicine & Public Health Medicine, Experimental Metastases Metastasis Multivariate analysis Neoplastic Cells, Circulating - pathology Oncology Platelets Prognosis Prospective Studies Prothrombin Retrospective Studies Thromboplastin Tumor cells D-dimers Circulating tumor cells Tumor derived extracellular vesicles Advanced breast cancer Platelets Diffuse intravascular coagulation
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Summary:	Purpose To 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. Methods In 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. Results In 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. Conclusion A 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0167-6806 1573-7217
DOI:	10.1007/s10549-021-06484-1