High Rate of Actionable Variants Identifed by Multigene Testing for Pancreas Cancer Patients in a High Risk Clinic

Abstract

Introduction: In 2017, the estimated incidence of pancreas cancer in the US was 53,670 with a 5-year survival of 8.2%. Whole exome research in pancreas cancer families has uncovered a diverse array of heritable causes of pancreas cancer, but current guidelines are insufficient to identify high-risk individuals. This study aims to determine the prevalence and spectrum of germline variants in patients attending a high-risk pancreas cancer genetics clinic with use of multigene germline panels. Methods: Data were drawn from patients referred to the GI/Genetics clinic at a tertiary comprehensive cancer center from June 2015 through December 2017. Patients were categorized by referral status based on personal history (P), family history (F) or both (P/F). Medical and family histories were evaluated by a team consisting of a cancer genetic counselor and a gastroenterologist who jointly determined if genetic testing was indicated. The rate of actionable germline variants by subgroup and overall was determined. Results: 96 patients were referred to the high-risk clinic. Germline testing was performed in 78 individuals after genetic counseling. 32 pathogenic or likely pathogenic variants were identified in 30 individuals. The most commonly encountered gene with a pathogenic variant was BRCA2 (n=7) followed by ATM, MSH2, MLH1, and PMS2 in order of decreasing prevalence. 24 patients were of Ashkenazi ancestry, harboring 8 pathogenic/likely pathogenic mutations. 7 patients were diagnosed with Lynch Syndrome. Of the 49 patients with family history of pancreas cancer alone, 19 patients (39%) were found to have pathogenic/likely pathogenic variants. Of the 21 patients with a personal history of pancreas cancer alone, 7 patients (33%) were found to have pathogenic/likely pathogenic variants. 8 patients were noted to have both personal and family histories of pancreas cancer; 4 (50%) had pathogenic variants. Conclusion: Thirty-eight percent of patients from a high-risk referral population with personal and/or family history of pancreas cancer who underwent germline testing were found to carry a pathogenic/likely pathogenic variant. The clinical utility of multigene panel testing in an enriched referral population is evident. The practice of panel testing is already widely accepted in the ovarian cancer population, and guidelines for germline screening for pancreas cancer patients in the modern era of multigene panels are overdue.24_A Figure 1. No Caption available.24_B Figure 2. No Caption available.24_C Figure 3. No Caption available.