Impact of BRCA1/2 somatic mutations in patients with pancreatic cancer in Girona: a population-based study

Abstract

Background and Aims ─ Pancreatic cancer remains one of the most lethal of malignancies and entails major health burden. The highly heterozygous nature of pancreatic cancer is partially responsible for its late diagnosis, therapeutic ineffectiveness and resistance. BRCA-1 and BRCA-2 gene mutations (which prevent DNA repair by homologous recombination) have been widely studied in patients with hereditary syndromes as predisposing factors for developing Pancreatic Cancer, as well as possible predictive factors for response to platinum-based chemotherapy. Even so, few information concerning BRCA-1 and BRCA-2 somatic mutations in Pancreatic Cancer is available. Knowledge about BRCA1/2 somatic mutations in Pancreatic Cancer may allow us to identify subgroups of patients with distinct biologic and therapeutic outcome. The aim of our study is to analyse the prevalence of Pancreatic Adenocarcinoma with BRCA somatic mutation in Girona’s province; to explore if there are significant differences in survival at 5 years between pancreatic cancer patients with or without BRCA1/2 somatic mutations; and, finally, to evaluate if patients treated with platinum-based chemotherapy compared with patients that did not receive platinum agents related with the presence or absence of BRCA1/2 somatic mutations , had an improvement of probability of overall survival at 36 months. Methods ─ We present a retrospective cohort trial that will enrol patients diagnosed of pancreatic cancer registered on the Girona’s Cancer Registry; 1407 patients will be enrolled from 1994 to 2012 using a non-probabilistic sampling. The mutation analyses will be done through PCR techniques and Next Generation Sequencing in all the available tumour samples. We will estimate the prevalence of BRCA1/2 somatic mutations in Girona’s province using a descriptive-univariate analysis. The 5-year survival rate will be studied on patients with pancreatic cancer harbouring BRCA1/2 mutations (n=191) and patients that do not present the tumour mutation (n=191). Besides, we will analyse the probability of survival at 36 months in Pancreatic Cancer patients harbouring BRCA1/2 somatic mutations and patients that do not present the mutation, that had been treated with platinum-based chemotherapy (n=190) or with non-platinum (n=190). The primary outcome measure will be the overall survival which will be analysed through bivariate and multivariate analyses