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

Abstract

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.

Pulmonary Tumor Thrombotic Microangiopathy in a Patient with Rapid Progressive Triple-Negative Breast Cancer

“…Histologically, fibrocellular intimal proliferation of small pulmonary vessels can be seen. This eventually can lead to stenosis and occlusion of the pulmonary vessels through the tumor cells themselves and through local release of tissue factors, leading to thrombosis due to activation of the coagulation system [5,11,12]. CTCs and CTC clusters are associated with severe outcome with rapid progression and early death in patients with metastatic breast cancer [13].…”

“…Recently, Gkountela et al [14] demonstrated that the ability of CTCs to form clusters has been linked to increased metastatic potential. Furthermore, there is an association between CTCs, circulating tumor microemboli, and intravascular coagulation activation in progressive breast cancer [9, 12]. In this patient, detection of CTCs and CTC clusters was not performed, but retrospectively, it might have been a relevant additional diagnostic test.…”

Predictive Nomogram for Hyperprogressive Disease During Anti-PD-1/PD-L1 Treatment in Patients with Advanced Non-Small Cell Lung Cancer

“… 31 Recently, Patel et al found a more than 10% incidence rate of prolonged APTT in patients treated with immune checkpoint inhibitors (ICIs). 32 , 33 Interestingly, lengthened APTT was also a poor prognostic factor for overall survival (OS) in patients with NSCLC, 34 gallbladder cancer, 35 multiple myeloma, 36 gastric cancer, 37 breast cancer, 38 and even COVID-1939. Importantly, we are the first to report that APTT is a key biomarker for predicting HPD triggered by ICI therapy.…”

A novel classifier combining G protein-coupled receptors and the tumor microenvironment is associated with survival status in glioblastoma

“…Moreover, the TME high group showed a negative correlation with the complement and coagulation cascades, while the TME low group displayed a negative association with the p53 signaling pathway (Supp Fig 2). Abnormal coagulation is a pathology recently found in different cancers ( Maruyama et al, 2022 ), which is related to the tumor thrombosis ( Dirix et al, 2022 ; Sun et al, 2022 ). Our study may propose a new function of GPCR in the pathology of abnormal coagulation, which deserves further experiments.…”