Germline BRCA1 mutations and pancreatic adenocarcinoma: A literature review.

Abstract

e15716 Abstract Background: Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer-related deaths in the United States. Although the vast majority of cases are sporadic, up to 10% of cases are related to a hereditary cancer predisposition syndrome, the most common of which is germline BRCA mutation. Although BRCA2 mutation has been well described in the literature, data on BRCA1 mutation-associated PAC is limited. This work aims at reviewing the literature on BRCA1 mutation-associated PAC and discussing the relevant findings. Methods: We have searched the Pubmed database for articles using the search terms “pancreatic”, “BRCA”, BRCA1”, “adenocarcinoma” or any combination of these keywords. Data about epidemiology, staging, prior history of other tumors, and management were collected. Systematic data extraction and assessments of quality were carried out by two reviewers, and good agreement was found. Results: A total of 13 studies were selected for review and included a total of 149 patients. The prevalence rate of PAC among patients with germline BRCA1 mutations ranged between 0.002% and 0.03%. Moreover, the prevalence of BRCA1 mutations in patients with BRCA-related PAC was found to be between 27% and 30%. Of note, PAC was diagnosed as the first tumor in 74% of patients with BRCA1-related PAC. The most common stage at diagnosis was stage 4 (56%) followed by stage 2 (22%). Conclusions: Germline BRCA1 mutation-associated PAC is an under-recognized entity when compared to BRCA2 mutations. Given the incredibly poor prognosis and the growing interest in targeted therapies, physicians need to be familiar with BRCA1 mutations as a possible etiology of PAC. A significant number of patients with BRCA1 mutation-associated PAC were diagnosed with PAC as the first tumor. Therefore, upper gastrointestinal screening should be considered in patients with germline BRCA1 mutations.