Abstract 885: A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO

Abstract

Abstract Introduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO), and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. Methods: We expanded the existing framework for PANCPRO and BRCAPRO to model underlying risk of pancreatic, breast, and ovarian cancer. We then validated this model on three datasets each reflecting the target populations for these models, including patients referred to a high-risk genetics clinic, patients with multiple family members with pancreatic cancer who underwent genetic testing for BRCA1/2, as well as a prospective registry of pancreatic cancer families. The new model is designated BRCAPANCPRO. Results: BRCAPANCPRO yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUC = 0.84, 95% CI: 0.78, 0.87) and was reasonably well-calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.82 [0.69, 0.94]). In these families, BRCAPANCPRO outperformed both the prior BRCAPRO and PANCPRO models. Discussion: The BRCAPANCPRO model improves the identification of families with a pathogenic variant in BRCA2 or BRCA1, particularly for families where there is the co-occurrence of pancreatic cancer in addition to breast and/or ovarian cancer. The model also improves the prediction of pancreatic cancer among families with a pancreatic cancer family history, with or without breast and/or ovarian cancer. Citation Format: Amanda L. Blackford, Erica J. Childs, Nancy Porter, Gloria Petersen, Kari Rabe, Steven Gallinger, Ayelet Borgida, Sapna Syngal, Ann Schwartz, Michele Cote, Ralph Hruban, Michael Goggins, Alison P. Klein, Giovanni Parmigiani. A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 885.