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Zentralbl Gynakol 2003; 125(9): 362-367
DOI: 10.1055/s-2003-43036
Originalarbeit

© Georg Thieme Verlag Stuttgart · New York

uPA und PAI-1 haben nicht nur eine prognostische, sondern auch eine prädiktive Bedeutung und unterstützen klinische Therapieentscheidungen beim primären Mammakarzinom

u-Plasminogen Activator (Urinary Plasminogen Activator, Urokinase) (uPA) and its PA-1 Type 1 Inhibitor are not only Prognostically but also Predictively Significant and Support Clinical Decisions on Therapy in Primary Carcinoma of the BreastN. Harbeck1 , C. Thomssen2
  • 1Frauenklinik der Technischen Universität München
  • 2Universitätsfrauenklinik Hamburg Eppendorf
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Publication History

Publication Date:
21 October 2003 (online)

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Zusammenfassung

uPA und PAI-1 sind die ersten neuen tumorbiologischen Prognosefaktoren beim Mammakarzinom, deren prognostische Bedeutung auf höchstem Evidenzniveau nachgewiesen wurde, und für die somit alle Evaluierungskriterien vor Überführung in die Klinik erfüllt sind. Patientinnen mit einem hohen Gehalt an uPA und/oder PAI-1 im Primärtumorgewebe haben eine signifikant geringere Heilungswahrscheinlichkeit als Patientinnen mit niedrigem uPA und PAI-1. Im Rahmen der mit dem Schmidt-Matthiesen-Preis 2002 ausgezeichneten Arbeit konnten wir erstmals zeigen, dass uPA und PAI-1 über ihre prognostische Bedeutung hinaus auch eine prädiktive Bedeutung hinsichtlich des Ansprechens auf adjuvante Chemotherapie besitzen. Patientinnen mit hohem uPA/PAI-1 haben einen signifikant größeren Nutzen von adjuvanter Chemotherapie als Patientinnen mit niedrigem uPA/PAI-1. Das Ansprechen auf adjuvante endokrine Therapie ist unabhängig vom uPA/PAI-1-Status. Die resultierende Frage nach der optimalen Chemotherapie für Patientinnen mit hohem uPA/PAI-1 versuchen derzeit in Deutschland die NNBC-3-Studie beim nodal-negativen Mammakarzinom (AGO, EORTC-RBG) sowie die ADEBAR-Studie bei Patientinnen mit ≥ 4 befallenen axillären Lymphknoten zu beantworten. Gleichzeitig legen diese Ergebnisse den frühzeitigen Einsatz neuer mit dem uPA-System interferierender tumorbiologischer Therapeutika in Kombination mit konventioneller Chemotherapie bei Patientinnen mit hohem uPA/PAI-1 nahe.

Abstract

uPA and PAI-1 are the first novel tumor biological prognostic factors in breast cancer for which the prognostic impact has been validated at the highest level of evidence and hence all evaluation criteria for transfer into clinical practice have been fullfilled. Breast cancer patients with high uPA and/or PAI-1 levels in their primary tumor tissue have a significantly lower chance for cure than patients with low levels of both uPA and PAI-1. Our research that was honored with the Schmidt-Matthiesen-Award 2002 shows for the first time that uPA and PAI-1 are not only prognostic factors but also have a predictive impact with regard to response to adjuvant chemotherapy. Patients with high uPA/PAI-1 derive a significantly greater benefit from adjuvant chemotherapy than patients with low uPA/PAI-1. Benefit from adjuvant endocrine therapy is independent of uPA/PAI-1 status. The resulting question about the optimal chemotherapy for patients with high uPA/PAI-1 is currently being addressed in Germany by the NNBC-3 trial in node-negative breast cancer (AGO, EORTC-RBG) as well as the ADEBAR trial in patients with 4 or more involved axillary lymph nodes. Moreover, our results suggest the use of novel therapeutic agents interfering with the uPA system together with conventional chemotherapy in patients with high uPA/PAI-1 already in early stage disease.

Schlüsselwörter

uPA - Mammakarzinom - NNBC-3 - nodal-negativ - PAI-1 - Prognose - Prädiktion von Therapieansprechen

Key words

uPA - PAI-1 - breast cancer - NNBC-3 - node-negative - prognosis - prediction of therapy response

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OÄ Priv.-Doz. Dr. med. Nadia Harbeck

Frauenklinik und Poliklinik, Klinikum rechts der Isar

Technische Universität München

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81675 München

Phone: 0 89/41 40-24 19

Fax: 0 89/41 40-48 46

Email: nadia.harbeck@lrz.tum.de