Validation of a combined residual risk score for healthy unaffected women presenting to breast cancer (BC) screening centers.

1507Background: Recent studies have identified single-nucleotide polymorphisms (SNPs) that individually confer modest risk but together explain genetic BC predisposition in many women testing negative for monogenic mutations. We have previously developed and validated an 86-SNP residual risk score (RRS) and a combined residual risk score (cRRS) that incorporates version 7.02 of the Tyrer-Cuzick (TC) model in large consecutive cohorts of women who tested negative for mutations in known BC predisposition genes during hereditary cancer testing. Here, we describe validation of the cRRS in a consecutive cohort of women enrolled from BC screening centers. Methods: This was a prospective, IRB-approved study conducted according to a case-control design. The primary objective was to demonstrate that cRRS offers significantly improved discriminatory accuracy compared to TC alone. A consecutive series of unaffected controls and recently diagnosed BC-affected cases of European ancestry who presented to screening cent...