LAUSR

1579Background: Women who are unaffected with cancer but have a significant family history of breast cancer (BC) are frequently referred for hereditary cancer testing with multi-gene panels; however, < 10% test positive for clinically actionable mutations. Large-scale genotyping studies have identified common variants (primarily single-nucleotide polymorphisms) that individually confer modest BC risk, but together may explain the genetic susceptibility for BC in many women without monogenic mutations. Here, we describe the development and validation of a polygenic residual risk score in a large, consecutive cohort of women who tested negative for mutations in known BC susceptibility genes. Methods: This IRB-approved study includes women of European ancestry tested with a multi-gene hereditary cancer panel who were negative for mutations in 11 genes associated with BC (BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, CHEK2, ATM, NBN, BARD1). Clinical information was collected from provider-completed test requ...