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[19] Level-1 evidence for prognostic and predictive impact of uPA and PAI-1 in node-negitive breast cancer provided by second schedule analysis of multicenter Chemo-N0 therapy trail.
Harbeck N. Meisner C, Prechtl A, Untch M. Selbmann H-K, Sweep F, Graeff H, Schmitt M, Jaenicke F, Thomssen C, far the Chemo N0 Study Group Frauenklinik, Technisch Universitael Muenchen, Munich, Germany; Institut fuer Medizinische Informationsverarbeltung, Universitaet Tuebingen, Germany; Frauenklinik Grosshadern, Ludwig-Maxunilians-Universitaet, Munich, Germany; Universitaetsfrauenklinik Eppendorf, Hamburg, Germany; Dept. of Chemical Endocrinology, University Medical Center Sint Radbound, Nijmegen, Metherlands
Abstract presented at the San Antonio Breast Symposium, Dec 2001.
Proteolytic factors uPA (urokinase-type plasminogen activator) and PAI-1 facilitate tumor invasion and metastasis. First analysis of the Chemo-N0 therapy trail confirmed the significant prognostic impact of uPA and PAI-1 in node-negitive breast cancer in a prospective randomized multicenter setting (Jaenicke et al, JNCI 93, 2001, in press).
After completion of the trail, we now present the second schedule interim analysis compromising 647 patients with a median follow-up of 50 months. Patients with low tumor levels of uPA and PAI-1 were observed only. Patients with high tumor levels of uPA and PAI-1 were randomly to combination chemotherapy or observation only. 283 patients had low levels uPA and PAI-1 and and 364 elevated levels of uPA and/or PAI-1. The actuarial 3-year recurrence rate for patients with low tumor levels of uPA and PAI-1 was 6.3% , that for those with high uPA an/or PAI-1 in the observation groups was 14.2% (p=0.009). High-risk patients in chemotherapy group had 36.9% lower estimated probability of disease recurrence than high risk patients receiving observation only (intention-to-treat analysis RR 0.63; 95% CI 0.33-1.20; p=0.16). In per-protocol analysis, the treatment benefit reached statistical significance (RR 0.42; 95% CI 0.02-0.87; p=0.019) for disease-free survival and persists with regard to overall survival.
Using uPA and PAI-1, about half the patients with node-negitive breast cancer are classified as low risk, for whom adjuvant chemotherapy may be avoided, and half as high risk, who appear to benefit from adjuvant chemotherapy. Hance, uPA and PAI-1 are the novel tumor biological factors reaching the highest level of evidence (LOEI) and thus ready for routine testing in order to establish risk-adapted individualized therapy strategies in node-negative breast cancer.
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