Prognostic and Predictive value of the Urokinase-Type Plasminogen Activator (uPA) and Its Inhibitors PAI-1 and PAI-2 in Operable Breast Cancer

Abstract

The present study on the prognostic and predictive value of serine proteases was conducted in 460 early breast cancer patients mostly treated with some kind of adjuvant systemic therapy: 156 received chemotherapy, 141 hormone therapy and 111 a combination of both. Already in univariate analysis PAI-1 was the only proteolytic factor with a significant impact on DFS, which was retained in multivariate analysis (p=0.020); PAI-2 showed borderline significance in univariate analysis (p=0.0503) and uPA did not present as a significant prognostic factor for DFS in our patient series. In a separate univariate analysis of DFS on patient subgroups defined by adjuvant systemic therapy, a higher risk of relapse associated with higher uPA and PAI-1 levels was found in the subgroup of patients who did not receive any treatment; this difference did not reach the level of significance, probably due to the small number (n=52) of patients in this group (HR 1.37; p=0.71 and HR 2.14; p=0.321, respectively). A higher risk of relapse was also found in the subgroup of patients treated with adjuvant chemotherapy (HR 1.44; p=0.381 and HR 2.48; p=0.003, respectively). In contrast, the bad prognostic impact of high uPA and PAI-1 levels was lost in the subgroup of patients treated with adjuvant hormone therapy (HR 0.79; p=0.693 and HR 0.26; p=0.204, respectively). The same observations were made for the uPA/PAI-1 combination. Our study confirmed the prognostic value of serine proteases in early breast cancer. In addition, it pointed to a possible predictive value of these tumor markers for response to adjuvant hormone therapy with tamoxifen, which should be confirmed in further studies.