Multicenter Validation of a Gene Expression–Based Prognostic Signature in Lymph Node–Negative Primary Breast Cancer

• DOI: 10.1200/jco.2005.03.9115
• Publication Date: 2006-02-28T01:34:26Z
• Authors: John A. Foekens; David Atkins; Yi Zhang; Fred C.G.J. Sweep; Nadia Harbeck; Angelo Paradiso; Tanja Cufer; Anieta M. Sieuwerts; Dmitri Talantov; Paul N. Span; Vivianne C.G. Tja...; Alfredo F. Zito; Katja Specht; Heinz Hoefler; Rastko Golouh; Francesco Schittulli; Manfred Schmitt; Louk V.A.M. Beex; Jan G.M. Klijn; Yixin Wang
• Keywords: Gene signature

We previously identified in a single-center study 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this was to validate gene an independent more diverse population LNN patients from multiple institutions.Using custom-designed DNA chips we analyzed the expression 76 genes RNA frozen tumor samples 180 who did not receive adjuvant systemic treatment.In validation, highly informative identifying with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 20.9), even when corrected traditional factors multivariate analysis (HR, 11.36; 2.67 48.4). actuarial 5- and 10-year metastasis-free survival were 96% (95% 89% 99%) 94% 83% 98%), respectively, good profile group 74% 64% 81%) 65% (53% 74%), respectively poor group. sensitivity 5-yr 90%, specificity 50%. positive negative predictive values 38% 29% 47%) 86% 97%), respectively. confirmed as strong factor subgroups estrogen receptor-positive patients, pre- postmenopausal sizes 20 mm or smaller. subgroup receptor-negative tumors considered too small perform separate analysis.Our data provide methodologic clinical multicenter validation predefined