Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients

Abstract

Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45–66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45–68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.

Tissue Plasminogen Activator Levels and Risk of Breast Cancer in a Case–Cohort Study on Italian Women: Results from the Moli-sani Study

“…18,19 Concerning fibrinolytic components, several studies have shown that elevated levels of the key enzymes of the fibrinolytic system are predictors of poor patient outcome. 6,17,20,21 Our results are in line with a recent study by Rhone et al, 21 which involved 85 women with primary BC without distant metastases and a control group of 60 postmenopausal women at the same age (45-66 years), showing that BC cases had higher tPA levels than controls. Moreover, they observed a significantly higher concentration of tPA in postmenopausal BC patients as compared with premenopausal cases.…”

“…Moreover, they observed a significantly higher concentration of tPA in postmenopausal BC patients as compared with premenopausal cases. 21 This mainly suggests that age and hormonal status strongly affect the biology of BC, and that tPA may lead to the development of metastasis through proteolytic degradation of the extracellular matrix.…”

“…4,5,7 Accordingly, tPA is involved not only in the dissolution of cross-linked fibrin, but also in extravascular proteolysis and tissue remodeling, resulting in a proangiogenic profile enabling tumor invasion, cancer cell migration, and spreading, affecting the growth of both tumor and vascular cells. [2][3][4][5]20,21 Moreover, it is recognized that the hemostatic system is activated in the majority of cancer patients. 8,17 On the other hand, in the last few decades, several studies have underlined the role of the hemostatic and fibrinolytic systems in the pathogenesis of several cardiovascular diseases.…”

Biomarkers of tumor invasiveness in proteomics (Review)

“…This association was confirmed in renal cell carcinoma (150) and breast cancer; higher concentrations of PAI1 have been shown to be associated with an aggressive phenotype and a poor prognosis, with a positive correlation has been found with MMP9 (151). Rhone et al further analyzed the clinicopathological determinants of patients with invasive breast cancer and found significantly higher PAI1 concentrations in patients with ductal carcinoma compared to those with lobular carcinoma, suggesting that a high PAI1 expression predisposes to a pro-coagulant environment expressed by simultaneous activation of coagulation and fibrinolysis suppression (152). Finally, PAI1 is now considered to be a prognostic factor, particularly in breast cancer, and Li et al recently reviewed the numerous tumor promoting factors involved in the modulation of PAI1 activity (153).…”

Central retinal vein occlusion in a patient with breast carcinoma

“…In malignancies, CRVO is considered a paraneoplastic process where dynamic interactions between the tumor cells, blood coagulation system, vascular endothelium, leucocytes and platelets contribute to the pathogenesis of CRVO. Rhone and colleagues have shown that the concentration of plasminogen activator inhibitor type 1 is increased and activity of tissue factor pathway inhibitor is reduced in patients with breast carcinoma [ 8 ]. These hematologic changes promote thrombosis.…”