title: 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.
authors.affiliation: Institute of Oncology, Ljubljana, Slovenia. tcufer@onko-i.si
authors.forename: T
authors.initials: T
authors.lastname: Cufer
authors.forename: S
authors.initials: S
authors.lastname: Borstnar
authors.forename: I
authors.initials: I
authors.lastname: Vrhovec
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis*; D011379:Prognosis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D014568:Urokinase-Type Plasminogen Activator