Multicenter validation of a gene expression-based prognostic signature in lymph node-negative primary XXXX .

@entity1 @entity172 @entity0 @entity5 @entity3
PURPOSE: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) @entity0 @entity1 . The aim of this study was to validate this gene signature in an independent more diverse population of LNN @entity1 from multiple institutions. @entity1 AND METHODS: Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen @entity5 samples from 180 LNN @entity1 who did not receive adjuvant systemic treatment. RESULTS: In this independent validation, the 76-gene signature was highly informative in identifying @entity1 with distant @entity3 within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant @entity3 -free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant @entity3 -free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of @entity172 receptor-positive @entity1 , pre- and postmenopausal @entity1 , and @entity1 with @entity5 sizes 20 mm or smaller. The subgroup of @entity1 with @entity172 receptor-negative @entity5 was considered too small to perform a separate analysis. CONCLUSION: Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN @entity0 @entity1 .
