Tissue Plasminogen Activator as a Possible Indicator of Breast Cancer Relapse: A Preliminary, Prospective Study.

Abstract

Simple SummaryBreast cancer is the most common malignant neoplasm and the leading cause of cancer death in women worldwide. The heterogeneity of breast cancer is a significant challenge facing modern medicine, especially at the stage of diagnosis. In recent years, a substantial role of fibrinolytic biomarkers in the pathogenesis of breast cancer has been proved as the primary cause capable of initiating local recurrence and metastasis to other organs. Due to its proteolytic properties, fibrinolytic protein activity may lead to subendothelial layer degradation and promote neoplastic cell motility. Thus, we examined the fibrinolytic profile markers’ prognostic value in predicting the disease’s relapse. Our studies indicate that the t-PA antigen and PAI-1 activity are biomarkers with high prognostic potential. We showed that a lower baseline plasma concentration of t-PA antigen and higher PAI-1 activity might be strong predictors for distant metastases and independent prognostic markers in breast cancer patients.(1) Background: The fundamental causes of breast cancer mortality are the cancer spread and hypercoagulability state. The study aimed to evaluate the prognostic efficacy of the fibrinolytic profile concerning 5-year follow-up. (2) Methods: We investigated the predictive potential of the plasma activity of urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) as well as antigen of tissue plasminogen activator (t-PA), u-PA, PAI-1, and PAI-1/t-PA and PAI-1/u-PA complexes in 41 breast cancer patients. The median follow-up was 66 months, with full evidence of the first event. (3) Results: A significantly lower level of PAI-1 antigen was noted in IBrC patients with lymph node involvement (N1) than in patients with free lymph node metastases (N0). According to ROC curve analysis, a t-PA antigen was the strongest predictor of disease relapse (the area under the curve, AUC = 0.799; p < 0.0006). Patients with PAI-1 activity < 3.04 U/mL had significantly better disease-free survival (DFS) compared to those with PAI-1 activity > 3.04 U/mL. Patients with both t-PA antigen lower than 1.41 ng/mL (cut-off according to median value) and lower than 1.37 ng/mL (cut-off according to ROC curve) had significantly shorter DFS (p = 0.0086; p = 0.0029). (4) Conclusions: The results suggest that a higher plasma t-PA antigen level or lower PAI-1 activity are linked to better outcomes in breast cancer patients.