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European randomised multicentre trial on risk-adapted adjuvant chemotherapy in node-negative breast cancer based on selection by tumorbiological prognostic factors


? Improved effectiveness of systemic adjuvant treatment in node-ne gative breast cancer patients by identification of patients at high risk for rel apse using the tumorbiological factors uPA (urokinase-type plasminogen activator ) and its inhibitor PAI-1.
? Confirmation and validation of the prognostic an d predictive significance of uPA/PAI-1 for breast cancer.
? Feasibility of a pplication to breast cancer patients in daily practic

Brief description
Optimal treatment of breast cancer patients represents a majo r clinical and health problem with a high socio-economic impact. Strong recommen dations ("consensus") were given to offer all patients some kind of adjuvant the rapy. Nevertheless, adjuvant therapy in patients with tumor-free axillary lympho nodes remains a matter of debate, as about 70 % of these patients are cured by s urgery alone. Unselected treatment would lead to an overtreatment in the vast ma jority of these patients. Therefore, high-risk patients should be selected for a djuvant therapy by validated prognostic factors.
Recent basic and clinical canc er research performed at the European level (see BIOMED-I Program: BMHI CT 93-13 46) demonstrated the key role of the tumor-associated protease urokinase-type pl asminogen activator (uPA) and its inhibitor PAI-1 in these processes. The uPA an d PAI- 1 contents of breast cancer tissue are shown to be the strongest independ ent prognostic factors in node-negative disease.
To promote transfer of these recent results derived from basic research into gen eral clinical practice a randomized clinical trial is mandatory. In this trial, node-negative patients with high values of uPA and/or PAI-1 should be randomized to adjuvant chemotherapy (6 cycles CMF) versus observation. Patients with low c ontent of both uPA and PAI-1 will only be observed (< 10% relapse rate). Twelve German clinical and scientific centers take part in the German Pilot Study. Sinc e the start of the study in 1993, about 50 % of the required 1000 patients have been recruited.
To accelerate transfer to clinical application, extension of th e project to the European level by a confirmatory study is mandatory. To reach t hese objectives, 13 clinical/scientific centers in Belgium, Denmark, France, Ire land, Italy, Netherlands, Spain will take part in the study as partners of a Con certed Action. The coordinating study center will be in Hamburg. Central data co llection and randomization will be conducted by the EORTC Central Office - Data Center in collaboration with the Statistical Center for the 12 German centers in Tbingen. A combined analysis of the data acquired by the two statistical center s will be possible after completion of both studies. Quality control of laborato ry data is performed by Department of Experimental Endocrinology (Nijmegen). As industrial partners, 4 companies in Austria, Germany and Sweden involved in deve lopment, production and distribution of reagents, antibodies and laboratory kits of tumor-biological factors will join the proposal.

breast cance r, node-negative patients, risk-adapted adjuvant chemotherapy, tumorbiological p rognostic factors, urokinase-type plasminogen activator, uPA, PAI-1, European mu lticentre trial.

Funding Scheme

CON - Coordination of research actions


52,Martinistrasse 52
20246 Hamburg