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

Maxime Look; Wim van Putten; Michael Duffy; Nadia Harbeck; Ib Jarle Christensen; Christoph Thomssen; Ronald Kates; Frédérique Spyratos; Mårten Fernö; Serenella Eppenberger-Castori; C. G. J. Fred Sweep; Kurt Ulm; Jean-Philippe Peyrat; Pierre-Marie Martin; Henri Magdelenat; Nils Brünner; Catherine Duggan; Björn W. Lisboa; Pär-Ola Bendahl; Véronique Quillien; Alain Daver; Gabriel Ricolleau; Marion Meijer-van Gelder; Peggy Manders; Edward W. Fiets; Marinus Blankenstein; Philippe Broët; Sylvie Romain; Günther Daxenbichler; Gudrun Windbichler; Tanja Cufer; Simona Borstnar; Willy Kueng; Louk Beex; Jan Klijn; Nial O’Higgins; Urs Eppenberger; Fritz Jänicke; Manfred Schmitt; John Foekens

doi:10.1160/TH02-11-0264

Thrombosis and Haemostasis, Table of Contents

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

Authors

Maxime Look

¹Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands
Wim van Putten

²Department of Statistics, Erasmus Medical Center Rotterdam, The Netherlands
Michael Duffy

³Department of Surgery, Conway Institute of Biomolecular and Biomedical Science, University College, Dublin, Ireland
Nadia Harbeck

⁴Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
Ib Jarle Christensen

⁵Finsen Laboratory, Copenhagen, Denmark
Christoph Thomssen

⁶Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Ronald Kates

⁴Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
Frédérique Spyratos

⁷Laboratoire de Biologie Tissulaire, St. Cloud, France
Mårten Fernö

⁸Department of Oncology, University Hospital, Lund, Sweden
Serenella Eppenberger-Castori

⁹Stiftung Tumorbank Basel, Department of Research, University Hospital of Basel, Basel, Switzerland
C. G. J. Fred Sweep

¹⁰Department of Chemical Endocrinology, University Hospital Nijmegen, The Netherlands
Kurt Ulm

⁴Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
Jean-Philippe Peyrat

¹¹Laboratoire d’Oncologie Moléculaire Humaine, Lille, France
Pierre-Marie Martin

¹²Faculté de Médecine, Secteur Nord, Marseille, France
Henri Magdelenat

¹³Institut Curie, Paris, France
Nils Brünner

¹⁴Institute Pharmacology and Pathobiology, Royal Veterinary and Agriculture University, Frederiksberg, Denmark
Catherine Duggan

³Department of Surgery, Conway Institute of Biomolecular and Biomedical Science, University College, Dublin, Ireland
Björn W. Lisboa

⁶Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Pär-Ola Bendahl

⁷Laboratoire de Biologie Tissulaire, St. Cloud, France
Véronique Quillien

¹⁵Laboratoire de Biologie, Centre Eugène Marquis, Rennes, France
Alain Daver

¹⁶Centre Paul Papin, Angers, France
Gabriel Ricolleau

¹⁷Centre René Gauducheau, St. Herblain, France
Marion Meijer-van Gelder

¹Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands
Peggy Manders

¹⁰Department of Chemical Endocrinology, University Hospital Nijmegen, The Netherlands
Edward W. Fiets

¹⁸University Medical Center Utrecht, Utrecht, The Netherlands
Marinus Blankenstein

¹⁸University Medical Center Utrecht, Utrecht, The Netherlands
Philippe Broët

¹³Institut Curie, Paris, France
Sylvie Romain

¹²Faculté de Médecine, Secteur Nord, Marseille, France
Günther Daxenbichler

¹⁹Universitätsklinik für Frauenheilkunde, Innsbruck, Austria
Gudrun Windbichler

¹⁹Universitätsklinik für Frauenheilkunde, Innsbruck, Austria
Tanja Cufer

²⁰Institut of Oncology, Ljubljana, Slovenia
Simona Borstnar

²⁰Institut of Oncology, Ljubljana, Slovenia
Willy Kueng

⁹Stiftung Tumorbank Basel, Department of Research, University Hospital of Basel, Basel, Switzerland
Louk Beex

¹⁰Department of Chemical Endocrinology, University Hospital Nijmegen, The Netherlands
Jan Klijn

¹Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands
Nial O’Higgins

²¹Department of Surgery, University College Dublin, Dublin, Ireland
Urs Eppenberger

⁹Stiftung Tumorbank Basel, Department of Research, University Hospital of Basel, Basel, Switzerland
Fritz Jänicke

⁶Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Manfred Schmitt

⁴Frauenklinik der Technische Universität München, Klinikum rechts der Isar, Munich, Germany
John Foekens

¹Department of Medical Oncology, Erasmus Medical Center Rotterdam, The Netherlands

Abstract

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

Full Text

References

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