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, Inhaltsverzeichnis

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

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

› Institutsangaben

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

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Referenzen

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