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. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.
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 cancerpatients. 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 cancerpatients. 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. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.
Authors: Henriqueta Coimbra Silva; Vera Alves; Luis Alcides Mesquita Nogueira; Manuel Santos Rosa; Lina Carvalho; Fernando Regateiro Journal: Med Oncol Date: 2011-06-03 Impact factor: 3.064
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Authors: Nadia Harbeck; Manfred Schmitt; Martina Vetter; Janna Krol; Daniela Paepke; Mathias Uhlig; Stefan Paepke; Fritz Jänicke; Anneke Geurts-Moespot; Gunter von Minckwitz; Fred Sweep; Christoph Thomssen Journal: Breast Care (Basel) Date: 2008-10-16 Impact factor: 2.860
Authors: Kenneth A Botkjaer; Elena I Deryugina; Daniel M Dupont; Henrik Gårdsvoll; Erin M Bekes; Cathrine K Thuesen; Zhuo Chen; Zhou Chen; Michael Ploug; James P Quigley; Peter A Andreasen Journal: Mol Cancer Res Date: 2012-10-04 Impact factor: 5.852
Authors: Lea M Beaulieu; Brandi R Whitley; Theodore F Wiesner; Sophie M Rehault; Diane Palmieri; Abdel G Elkahloun; Frank C Church Journal: Bioessays Date: 2007-10 Impact factor: 4.345
Authors: Songdong Meng; Debu Tripathy; Sanjay Shete; Raheela Ashfaq; Hossein Saboorian; Barbara Haley; Eugene Frenkel; David Euhus; Marilyn Leitch; Cynthia Osborne; Edward Clifford; Steve Perkins; Peter Beitsch; Amanullah Khan; Larry Morrison; Dorothee Herlyn; Leon W M M Terstappen; Nancy Lane; Jianqiang Wang; Jonathan Uhr Journal: Proc Natl Acad Sci U S A Date: 2006-11-01 Impact factor: 11.205
Authors: Maria D Corte; Juan A Rodil; Julio Vázquez; Lucia García; Juan C Rodríguez; Miguel Bongera; José C Fernández; Luis O González; Ma Luz Lamelas; Maite Allende; José L García-Muñiz; Antonio Fueyo; Francisco J Vizoso Journal: J Cancer Res Clin Oncol Date: 2005-11-01 Impact factor: 4.553