Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer

Nadia Harbeck; Ronald E. Kates; Katja Gauger; Amina Willems; Marion Kiechle; Viktor Magdolen; Manfred Schmitt

doi:10.1160/TH03-12-0798

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2004; 91(03): 450-456
DOI: 10.1160/TH03-12-0798

Theme Issue Review Article

Schattauer GmbH

Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer

Authors

Nadia Harbeck

¹Department of Obstetrics and Gynecology,Technical University of Munich, Germany
Ronald E. Kates

¹Department of Obstetrics and Gynecology,Technical University of Munich, Germany
Katja Gauger

¹Department of Obstetrics and Gynecology,Technical University of Munich, Germany
Amina Willems

¹Department of Obstetrics and Gynecology,Technical University of Munich, Germany
Marion Kiechle

¹Department of Obstetrics and Gynecology,Technical University of Munich, Germany
Viktor Magdolen

¹Department of Obstetrics and Gynecology,Technical University of Munich, Germany
Manfred Schmitt

¹Department of Obstetrics and Gynecology,Technical University of Munich, Germany

Abstract

Summary

Urokinase-type plasminogen activator (uPA) and its inhibitor, PAI-1, play a key role in tumor invasion and metastasis. They were the first novel tumor biological factors to be validated at the highest level of evidence (LOE I) regarding their clinical utility in breast cancer. Their antigen levels are determined in tumor tissue extracts by standardized, quality-assured immunometric assays (ELISA). Since the late 1980s, numerous independent studies have demonstrated that patients with low levels of uPA and PAI-1 in their primary tumor tissue have a significantly better survival than patients with high levels of either factor. These prognostic data have recently been validated by an EORTC (European Organization for Research and Treatment of Cancer) pooled analysis comprising more than 8,000 breast cancer patients. In addition, results from a multicenter prospective randomized therapy trial in node-negative breast cancer (“Chemo N₀”) showed that node-negative breast cancer patients with low levels of uPA and PAI-1 in their primary tumor have a very good prognosis, and may thus be candidates for being spared the burden of adjuvant chemotherapy. In contrast, node-negative patients with high uPA/PAI-1 are at substantially increased risk of disease recurrence, comparable to that of patients with three or more tumor cell positive axillary lymph nodes. The “Chemo N₀” trial as well as retrospective data also indicate that these high-risk patients benefit from adjuvant chemotherapy. In conclusion, over a period of about 15 years sufficient evidence has been put forward to demonstrate that determination of uPA and PAI-1 in primary breast cancer patients supports risk-adapted individualized therapy decisions, particularily in patients with node-negative disease.

Keywords

Adjuvant therapy - metastasis - node-negative breast cancer - PAI-1 - prognosis - prediction of therapy response - risk group assessment - uPA

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Referenzen

References
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