Author/Editor		Look, Maxime P; van Putten, Wim LJ; Duffy, Michael J; Harbeck, Nadia; Christensen, Ib Jarle; Thomsen, Christoph; Kates, Ronald; Spyratos, Frederique; Fernoe, Marten; Čufer, Tanja; Borštnar, Simona
Title		Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients
Type		članek
Source		J Natl Cancer Inst
Vol. and No.		Letnik 94, št. 2
Publication year		2002
Volume		str. 116-28
Language		eng
Abstract		Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. (Abstract truncated at 2000 characters).
Descriptors		BREAST NEOPLASMS PLASMINOGEN ACTIVATOR INHIBITOR 1 UROKINASE BIOLOGICAL MARKERS AGE FACTORS PROGNOSIS PROPORTIONAL HAZARDS MODELS SURVIVAL ANALYSIS