Developing Surveillance Strategy for Pancreatic Cancer High Risk Population

Background: Pancreatic cancer (PC) is the third leading cause of cancer death in the US, with a lifetime risk of 1.5%. The 5-year survival rate is 7.2%, the poorest survival rate of any common malignancy. PC development from a small precancerous lesion into a tumor is a relatively slow process, emphasizing the importance of screening of high-risk individuals. However, at this time point candidate population and benefits from screening is still unclear.

Aims: We have established a high-risk pancreatic cancer clinic with the aims of: improving survival of individuals at high-risk for pancreatic cancer and identifying genetic alterations and risk factors associated with familial PC.

Materials and methods: We have recruited 230 high-risk PC individuals for genetic screening and clinical surveillance. Genetic testing included BRCA1,2 mutations panel and whole exome sequencing (WES) that was performed on 42 individuals with negative BRCA panel results.

Results: Out of the 230 individuals recruited, 134 (58%) fulfilled accepted high-risk PC criteria of two first degree or 3 PC members in the family and 76 individuals (33% of the 230) were found to carry a pathogenic mutation. BRCA1,2 mutations were most frequently found in our cohort (25%), followed by ATM (4%). Whole exome sequencing (WES) revealed a wide variety of genetic changes that would not have been detected, if testing was limited to multi-gene panels.

Conclusions: Identifying high-risk pancreatic cancer individuals may help stratify surveillance and improved survival. WES genetic evaluation may help in classifying these high-risk individuals.