BRCA1 and BRCA2 Germline Mutations Are Frequently Demonstrated in a Pancreatic Ductal Adenocarcinoma Cohort Referred For Genetic Testing

Abstract

Purpose: Ten percent of pancreatic ductal adenocarcinoma (PDAC) is due to a genetic predisposition including the BRCA1/2 germline mutations. Patients with a prior diagnosis of PDAC were referred to our high risk pancreatic prevention and genetics program and offered genetic counseling and if appropriate, evaluation for possible predisposing mutations. Our aim was to determine the prevalence of BRCA 1/2 germline mutations in this PDAC cohort. Methods: Patients were referred to our program after a diagnosis of PDAC. After meeting with a clinician and genetic counselor, patients underwent genetic testing for BRCA1/2 mutations (multisite 3 for Ashkenazi Jewish (AJ) patients and comprehensive testing for all others). Results: Thirty-two patients underwent BRCA1 and BRCA2 genetic testing following a diagnosis of PDAC. The mean age was 60.2, 59.3% male, 81.3% AJ, 100% Caucasian. Five of 24 patients were demonstrated to have AJ founder mutations (two BRCA1, three BRCA2), and 2 of 8 patients had a BRCA2 mutation on comprehensive testing. The diagnostic yield was 7/32 (21.8%). The mean age of PDAC diagnosis amongst BRCA1/2 mutation carriers was 54.5 years (range 48-66, SD 8.55) compared to 61.5 years (range 35-82, SD 11.97, p=.19) for those without a mutation. None of the PDAC patients who tested positive for BRCA1/2 mutations had a history of tobacco use or heavy alcohol use. Only two patients had a first degree relative with a BRCA1/2 related cancer. None of the seven BRCA1/2 mutation carriers had any first- or second degree relatives with PDAC, although one 49 year-old patient with a BRCA2 mutation had three third-degree relatives with PDAC. Conclusion: We demonstrate a high diagnostic yield of 21.8% for BRCA1 and BRCA2 mutations in a cohort of PDAC patients referred to our pancreatic prevention and genetics program. Those who tested positive for BRCA1/2 mutations had a trend towards a younger age at PDAC diagnosis. There was a notable absence of PDAC and very few BRCA related cancers in first degree relatives of BRCA1/2 carriers. Even in the absence of a family history of breast and ovarian cancer, especially in the AJ population, clinical BRCA1 and BRCA2 testing for risk stratification and family counseling should be considered in patients with a personal or family history of PDAC.