Outcome Prediction in Node-Negative Breast Cancer Based on ASCO-Recommended Biomarkers uPA/PAI-1 Using the Final 10-Year Analysis of the Randomized Multicenter Chemo N0 Trial Compared to Adjuvant Online™.

Background: Based on interim analysis of Chemo N0, the first prospective multicenter randomized clinical trial using biomarkers uPA/PAI-1 for risk stratification and chemotherapy selection in N0 breast cancer, uPA/PAI-1 are now recommended for routine use by ASCO and AGO guidelines. Final 10-year follow-up of Chemo N0 has validated the clinically relevant long-term prognostic and predictive impact of uPA/PAI-1 in N0 breast cancer. To quantify the clinical utility of this impact, outcomes in subgroups defined by these biomarkers were compared to predictions of Adjuvant Online™, the leading validated tool based on established clinical factors. Methods: In Chemo N0, patients (n=647, 1993-98) were prospectively stratified according to uPA/PAI-1: High-risk patients were randomized (6x CMF vs. observation), low-risk patients observed. Retrospectively, we divided recruited patients into two groups (chemotherapy vs. no adjuvant therapy) and stratified using uPA/PAI-1 (low vs. high). Individual 10-year OS was calculated by www.adjuvantonline.org (Version 7.0); these estimated values were compared to the observed Chemo N0 10-year OS. Results: 383/647 patients have complete 10-year follow-up data. Median 10-year OS estimated by Adjuvant Online™ was 80.5% taking into account administered adjuvant therapy; 10-year Chemo N0 follow-up revealed observed 10-year OS of 74.7% (97/383 died). 77.8% (298/383) did not receive chemotherapy: In high-risk, untreated patients (n=137), 10-year OS was 72.3% vs. estimated 81.1%. In CMF-treated patients (all high-risk, n=85), observed OS was 61.2% vs. estimated 76.4%. Conclusions: For the first time, risk assessment by novel biomarkers is compared to that by Adjuvant Online™ in final data from a randomized prospective clinical trial. In patients with high uPA/PAI-1, the individual 10-year risk calculated by Adjuvant Online™ seems to be underestimated compared to observed patient outcome. Tumor-biological information provided by validated biomarkers thus has the potential of enhancing epidemiology-based risk estimation using only established factors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4038.