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

Abstract

(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.

Understanding Breast Cancer Aggressiveness and Its Implications in Diagnosis and Treatment

“…Cancer treatment includes surgery, chemotherapy, radiotherapy, hormone therapy, and immunotherapy. BC treatment is more difficult after metastasis and recurrence [ 2 ]. Relapses are linked to multi-drug resistance (MDR) characteristics such as increased efflux transporter expression and activation of transcription factor genes that lead to mutations and proliferation of cancer cells [ 3 ].…”

“…Tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor-1 (PAI-1) have been recently described as biomarkers with high prognostic potential. A clinical study demonstrated that low plasma concentrations of t-PA antigen and higher PAI-1 activity are shown to be strong predictors for distant metastasis and independent prognostic markers in BC patients [ 2 ].…”

Acquired hyperfibrinolysis as the presenting sign of metastatic breast cancer: A case report

“…Winther-Larsen et al (18) systematically evaluated hyperfibrinolysis in 21 patients with malignant solid tumors, with prostate cancer (76%) being the most common type, while there have been few reports of hyperfibrinolysis in patients with breast cancer (17,21). Breast cancer cells contain abundant plasminogen activators (t-PA and u-PA), and with the progression of tumors, plasminogen activator in tumor cells is released into the blood in large amounts, causing enhanced fibrinolytic system function (22)(23)(24). ii) The tumor cell membrane also carries a specific u-PA-receptor (u-PAR), which contributes to the assembly of fibrinolytic components and promotes the activation of the fibrinolytic cascade (24,25).…”

“…Breast cancer cells contain abundant plasminogen activators (t-PA and u-PA), and with the progression of tumors, plasminogen activator in tumor cells is released into the blood in large amounts, causing enhanced fibrinolytic system function (22)(23)(24). ii) The tumor cell membrane also carries a specific u-PA-receptor (u-PAR), which contributes to the assembly of fibrinolytic components and promotes the activation of the fibrinolytic cascade (24,25).…”

ALDH1A3 promotes invasion and metastasis in triple‐negative breast cancer by regulating the plasminogen activation pathway

“…Other studies have investigated associations between cancer progression and serum levels of tPA (not in tumours). For example, low plasma/serum level of tPA was associated with poor disease‐free survival and enhanced risk of breast cancer progression [ 61 ]. While, in other studies, higher levels of plasma tPA are linked to a greater risk of breast cancer and aggressive disease [ 62 , 63 , 64 ].…”