P078: Genomic ascertainment of PALB2-related cancer predisposition

The Partner and Localizer of BRCA2 (PALB2) interacts with both BRCA2 and BRCA1 to ensure genomic stability via homologous recombination repair of DNA double-stranded breaks. Elevated cancer risk in female and male breast, pancreas and ovarian cancer in individuals harboring a pathogenic variant in PALB2 is well-established, with no consistent evidence for increased risk of other cancers. However, most of these studies have been ascertained through a personal or family history of cancer. What is not known is the magnitude of cancer risk when PALB2 pathogenic variation is genomically ascertained, for example through opportunistic screening (eg, a secondary findings) or incidentally, nor how this risk is influenced by a family history of cancer.