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Thromb Haemost 2003; 90(03): 538-548
DOI: 10.1160/TH02-11-0264
Cellular Proteolysis and Oncology
Schattauer GmbH

Pooled analysis of prognostic impact of uPA and PAI-1 in breast cancer patients

Maxime Look
1   Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands
,
Wim van Putten
2   Department of Statistics, Erasmus Medical Center Rotterdam, The Netherlands
,
Michael Duffy
3   Department of Surgery, Conway Institute of Biomolecular and Biomedical Science, University College, Dublin, Ireland
,
Nadia Harbeck
4   Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
,
Ib Jarle Christensen
5   Finsen Laboratory, Copenhagen, Denmark
,
Christoph Thomssen
6   Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
,
Ronald Kates
4   Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
,
Frédérique Spyratos
7   Laboratoire de Biologie Tissulaire, St. Cloud, France
,
Mårten Fernö
8   Department of Oncology, University Hospital, Lund, Sweden
,
Serenella Eppenberger-Castori
9   Stiftung Tumorbank Basel, Department of Research, University Hospital of Basel, Basel, Switzerland
,
C. G. J. Fred Sweep
10   Department of Chemical Endocrinology, University Hospital Nijmegen, The Netherlands
,
Kurt Ulm
4   Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
,
Jean-Philippe Peyrat
11   Laboratoire d’Oncologie Moléculaire Humaine, Lille, France
,
Pierre-Marie Martin
12   Faculté de Médecine, Secteur Nord, Marseille, France
,
Henri Magdelenat
13   Institut Curie, Paris, France
,
Nils Brünner
14   Institute Pharmacology and Pathobiology, Royal Veterinary and Agriculture University, Frederiksberg, Denmark
,
Catherine Duggan
3   Department of Surgery, Conway Institute of Biomolecular and Biomedical Science, University College, Dublin, Ireland
,
Björn W. Lisboa
6   Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
,
Pär-Ola Bendahl
7   Laboratoire de Biologie Tissulaire, St. Cloud, France
,
Véronique Quillien
15   Laboratoire de Biologie, Centre Eugène Marquis, Rennes, France
,
Alain Daver
16   Centre Paul Papin, Angers, France
,
Gabriel Ricolleau
17   Centre René Gauducheau, St. Herblain, France
,
Marion Meijer-van Gelder
1   Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands
,
Peggy Manders
10   Department of Chemical Endocrinology, University Hospital Nijmegen, The Netherlands
,
Edward W. Fiets
18   University Medical Center Utrecht, Utrecht, The Netherlands
,
Marinus Blankenstein
18   University Medical Center Utrecht, Utrecht, The Netherlands
,
Philippe Broët
13   Institut Curie, Paris, France
,
Sylvie Romain
12   Faculté de Médecine, Secteur Nord, Marseille, France
,
Günther Daxenbichler
19   Universitätsklinik für Frauenheilkunde, Innsbruck, Austria
,
Gudrun Windbichler
19   Universitätsklinik für Frauenheilkunde, Innsbruck, Austria
,
Tanja Cufer
20   Institut of Oncology, Ljubljana, Slovenia
,
Simona Borstnar
20   Institut of Oncology, Ljubljana, Slovenia
,
Willy Kueng
9   Stiftung Tumorbank Basel, Department of Research, University Hospital of Basel, Basel, Switzerland
,
Louk Beex
10   Department of Chemical Endocrinology, University Hospital Nijmegen, The Netherlands
,
Jan Klijn
1   Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands
,
Nial O’Higgins
21   Department of Surgery, University College Dublin, Dublin, Ireland
,
Urs Eppenberger
9   Stiftung Tumorbank Basel, Department of Research, University Hospital of Basel, Basel, Switzerland
,
Fritz Jänicke
6   Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
,
Manfred Schmitt
4   Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
,
John Foekens
1   Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands
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Weitere Informationen

Publikationsverlauf

Received 18. November 2003

Accepted after resubmission 02. Juni 2003

Publikationsdatum:
05. Dezember 2017 (online)

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Summary

In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-1 for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-1 survival analyses, reflecting the interaction between nodal status and uPA/PAI-1. The estimates for uPA and PAI-1 were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-1 were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-1 are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.

Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Keywords

Pooled-analysis - uPA - PAI-1 - breast cancer - prognosis
 

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