© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 2, 116-128,
January 16, 2002
© 2002 Oxford University Press
ARTICLE |
Pooled Analysis of Prognostic Impact of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in 8377 Breast Cancer Patients
Affiliations of authors: M. P. Look, M. E. Meijer-van Gelder, J. G. M. Klijn, J. A. Foekens, (Department of Medical Oncology), W. L. J. van Putten (Department of Statistics), Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, The Netherlands; M. J. Duffy, C. Duggan, St. Vincent's University Hospital, Dublin, Ireland; N. Harbeck, R. Kates, K. Ulm, M. Schmitt, Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany; I. J. Christensen, N. Brünner, Finsen Laboratory, Copenhagen, Denmark; C. Thomssen, B. W. Lisboa, F. Jänicke, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; F. Spyratos, Laboratoire de Biologie Tissulaire, St. Cloud, France; M. Fernö, P. O. Bendahl, Department of Oncology, University Hospital, Lund, Sweden; S. Eppenberger-Castori, W. Kueng, U. Eppenberger, Stiftung Tumorbank Basel, Department of Research, University Hospital of Basel, Switzerland; C. G. J. Sweep, P. Manders, L. V. A. M. Beex, Department of Chemical Endocrinology, University Hospital Nijmegen, The Netherlands; J. P. Peyrat, Laboratoire d'Oncologie Moléculaire Humaine, Centre Oscar Lambret, Lille, France; P. M. Martin, S. Romain, Laboratoire de Transfert d'Oncologie Biologie, Marseille, France; H. Magdelenat, P. Broët, Institut Curie, Paris, France; V. Quillien, Laboratoire de Biologie, Centre Eugéne Marquis, Rennes, France; A. Daver, Centre Paul Papin, Angers, France; G. Ricolleau, Centre René Gauducheau, St. Herblain, France; W. E. Fiets, M. A. Blankenstein, University Medical Center Utrecht, The Netherlands; G. Daxenbichler, G. Windbichler, Universitätsklinik für Frauenheilkunde, Innsbruck, Austria; T. Cufer, S. Borstnar, Institut of Oncology, Ljubljana, Slovenia; N. O'Higgins, University College Dublin, Ireland.
Correspondence to: Maxime P. Look, MSc., Josephine Nefkens Institute, Rm. Be 428, P. O. Box 1738, 3000 DR Rotterdam, The Netherlands (e-mail: look{at}bidh.azr.nl).
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.
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|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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N. Harbeck, R. E. Kates, M. P. Look, M. E. Meijer-van Gelder, J. G. M. Klijn, A. Kruger, M. Kiechle, F. Janicke, M. Schmitt, and J. A. Foekens Enhanced Benefit from Adjuvant Chemotherapy in Breast Cancer Patients Classified High-Risk according to Urokinase-type Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor Type 1 (n = 3424) Cancer Res., August 15, 2002; 62(16): 4617 - 4622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
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