Artikel
Molecular risk estimation and adjuvant chemotherapy in node-negative breast cancer patients - a status report of the prospective clinical trial NNBC 3-Europe
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Autoren
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Daniela Paepke
- Frauenklinik, Klinikum rechts der Isar der TU München, Germany, Deutschland
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F. Herbst
- Klinik fuer Gynaekologie, Universitaetskrankenhaus Hamburg-Eppendorf, Germany
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K. Annecke
- Frauenklinik, Klinikum rechts der Isar der TU München, Germany
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N. Gaskill
- Klinik fuer Gynaekologie, Universitaetskrankenhaus Hamburg-Eppendorf, Germany
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F. Sweep
- Experimental and Chemical Endocrinology, University Hospital Nijmegen, The Netherlands
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D. Augustin
- Klinikum Deggendorf Germany
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C. Meisner
- Institute fuer Medizinische Datenverarbeitung, Universitaet Tuebingen, Germany
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M. Schmidt
- Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde, Universität Mainz, Germany
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M. Schmitt
- Frauenklinik, Klinikum rechts der Isar der TU München, Germany
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F. Jaenicke
- Klinik fuer Gynaekologie, Universitaetskrankenhaus Hamburg-Eppendorf, Germany
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N. Harbeck
- Frauenklinik, Klinikum rechts der Isar der TU München, Germany
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C. Thomssen
- Klinik für Gynaekologie, Martin-Luther-Universitaet Halle, Germany
| Veröffentlicht: | 20. März 2006 |
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Gliederung
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Background: Risk assessment in node negative breast cancer patients by the use of the invasion markers urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 has been demonstrated in several studies and a large meta analysis. Patients with low uPA and/or PAI-1 tumor levels have an excellent 5-year overall survival (>95%) even without adjuvant therapy. The use of these molecular markers has shown to spare adjuvant chemotherapy in approximately one half of all node-negative breast cancer patients; whereas patients with an intermediate grade tumor can easily be differentiated in low and high risk. In addition, patients with high uPA and/or PAI-1 levels seem to have a benefit from adjuvant chemotherapy.
The NNBC-3-Europe trial seeks to answer two questions:
1) Is risk assessment by the molecular markers uPA/PAI-1 superior to that by clinico-pathological factors with regard to identification of low-risk patients?
2) Is adjuvant chemotherapy using an anthracycline-taxane containing sequence (FEC-Docetaxel) superior to standard FEC in high-risk patients?
Methods: In the NNBC 3-Europe trial, participating centres opt to either perform risk estimation by clinico-pathological factors or by the invasion markers uPA/ PAI-1. Low-risk patients will be then observed without adjuvant chemotherapy. High-risk patients are randomised to adjuvant chemotherapy. All patients with hormone receptor positive tumors receive endocrine therapy.
Results: Of the first 506 patients in the study arm with the biological risk assessment, 62 had a grade 1 tumor, and 184 had grade 3 tumors. Among grade 2 tumors (n=260),87 had low levels of uPA .173 patients presented with elevated values. Overall, 30% of the patients were allocated to the low-risk group.
Conclusion: An adjuvant chemotherapy trial based on uPA/PAI-1 determination in the primary tumor is feasible in a multicentre setting. Applying these molecular markers for risk assessment, at this stage of the study, for almost on third of the patients an adjuvant chemotherapy could be spared. The study is planned to recruit 5.700 patients. This study is performed in association with the EORTC Receptor and Biomarker Group and the German AGO Breast Group.
