Medline ® Abstract for Reference 146
of 'Prognostic and predictive factors in early, nonmetastatic breast cancer'
Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1.
Jänicke F, Prechtl A, Thomssen C, Harbeck N, Meisner C, Untch M, Sweep CG, Selbmann HK, Graeff H, Schmitt M, German N0 Study Group
J Natl Cancer Inst. 2001;93(12):913.
BACKGROUND: Most patients with lymph node-negative breast cancer are cured by locoregional treatment; however, about 30% relapse. Because traditional histomorphologic and clinical factors fail to identify the high-risk patients who may benefit from adjuvant chemotherapy, other prognostic factors are needed. In a unicenter study, we have found that levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in the primary tumor are predictive of disease recurrence. Thus, we designed the Chemo N(0) prospective randomized multicenter therapy trial to investigate further whether uPA and PAI-1 are such prognostic factors and whether high-risk patients identified by these factors benefit from adjuvant chemotherapy. After 4.5 years, we present results of the first interim analysis.
METHODS: We studied 556 patients with lymph node-negative breast cancer. The median follow-up was 32 months. All patients with low tumor levels of uPA (<or = 3 ng/mg of protein) and of PAI-1 (<or = 14 ng/mg of protein) were observed. Patients with high tumor levels of uPA (>3 ng/mg of protein) and/or of PAI-1 (>14 ng/mg of protein) were randomly assigned to combination chemotherapy or subjected to observation only. All statistical tests were two-sided.
RESULTS: A total of 241 patients had low levels of uPA and PAI-1, and 315 had elevated levels of uPA and/or PAI-1. The estimated 3-year recurrence rate for patients with low tumor levels of uPA and PAI-1 (low-risk group) was 6.7% (95% confidence interval [CI]= 2.5% to 10.8%). This rate for patients with high tumor levels of uPA and/or PAI-1 (high-risk group) was 14.7% (95% CI = 8.5% to 20.9%) (P = 0.006). First interim analysis suggests that high-risk patients in the chemotherapy group benefit, with a 43.8% lower estimated probability of disease recurrence at 3 years than high-risk patients in the observation group (intention-to-treat analysis: relative risk = 0.56; 95% CI = 0.25 to 1.28), but further follow-up is needed for confirmation.
CONCLUSIONS: Using uPA and PAI-1, we have been able to classify about half of the patients with lymph node-negative breast cancer as low risk, for whom adjuvant chemotherapy may be avoided, and half as high risk, who appear to benefit from adjuvant chemotherapy.
Universitäts-Frauenklinik Eppendorf, Hamburg, Germany.