DYNAMICS OF HEMOSTATIC MARKERS THROUGHOUT SYSTEMIC TREATMENT IN PATIENTS WITH BREAST CANCER

Abstract

Breast cancer is the most commonly diagnosed cancer among women globally and is increasingly managed with complex multimodal systemic therapy. Despite advances in oncologic treatment, venous thromboembolism (VTE) is still a major health problem and the second leading cause for cancer-related mortality. Patients with breast cancer have roughly a fourfold higher risk of developing VTE compared with age- and sex-matched healthy controls, and this risk is further amplified by systemic chemotherapy and other adjuvant treatments. The prothrombotic tendency in breast cancer arises from a complex interaction between tumor biology, host response, and anticancer therapy. Tumor cells can directly activate coagulation by expressing tissue factor (TF) and releasing TF-bearing extracellular vesicles, thereby initiating thrombin generation and fibrin formation. Prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT) are clinical-laboratory parameters, which provide a direct measure of in vivo thrombin formation. D-dimer is widely used in clinical practice as an indicator of ongoing coagulation and fibrinolysis. In cancer patients, the coagulation system is often chronically activated and AT III, a natural anticoagulant, may be consumed through ongoing inhibition of thrombin and factor Xa or down-regulated. Objective: To investigate longitudinal changes in hemostatic markers – F1+2, TAT, D-dimer, TF, fibrinogen and Antithrombin III in patients with breast cancer undergoing systemic treatment. Materials and methods: We investigated 38 women with breast cancer. A control group of 34 age-matched healthy women was also studied. TAT, F1+2, TF, D-dimer, AT III and fibrinogen levels were determined prior to therapy initiation – Visit 1; Visit 2 – monitoring of therapeutic response; Visit 3 – after completing treatment. ELISAs were used to quantify F1+2, TF and TAT. Fibrinogen levels were determined by the Claus clotting method, AT III activity by chromogenic assay, and plasma D-dimer concentration by immunoturbidimetry. Results: Levels of F1+2, TAT, TF and D-dimer declined throughout systemic therapy, with baseline values being significantly higher than those at visits 2 and 3 (P<0.05). ATIII activity showed a statistically significant increase at visit 3 compared to visit 2 (P=0.023). Conclusion: Systemic treatment in breast cancer patients significantly influenced the dynamics of hemostatic markers. A hypercoagulable state persists during the applied therapy, despite the tendency for lower levels of TAT, F1+2, TF, D-dimer and increased AT III activity. This highlights the importance of an individualized anticoagulation strategy aimed at preventing thrombotic events and effectively managing cancer-related venous thromboembolism.