Hood on the Association Between BRCA Mutations and Primary Tumor Location in PDAC

Ryan Hood, BA, MD/MPH student, University of Miami Miller School of Medicine, discusses findings from a study investigating the association between BRCA1/2 pathogenic variants, primary tumor location, and metastatic organotropism in patients with pancreatic ductal adenocarcinoma (PDAC).

This retrospective study used information from a database to evaluate patients with PDAC harboring BRCA1/2 pathogenic variants, as well as a matched control cohort of BRCA1/2 wild-type patients. Hood and colleagues found a positive connection between cancers in the body and tail of the pancreas with homologous recombination deficiency mutations, meaning that patients with BRCA1/2-mutated disease were more likely to have cancers in those areas of the pancreas, at 51.6% vs 31.0% (P < .001), Hood reports.

Furthermore, after adjustment for primary location, patients with BRCA1/2 mutations were less likely to have metastatic disease spread to the peritoneum vs control patients (odds ratio, 0.43; 95% CI, 0.21-0.89). Patients with BRCA1/2-mutated cancers in the body and tail of the pancreas had a significantly slower rate of peritoneal spread compared with those with body and tail tumors and BRCA1/2 wild-type disease (OR, 0.41; 95% CI, 0.20-0.83). However, no significant association was observed between the presence of BRCA1/2 mutations and peritoneal spread in patients with masses in the head of the pancreas (OR, 1.09; 95% CI, 0.48-2.5), he states.

Finally, using somatic sequencing data, investigators found that the presence of BRCA1/2 pathogenic variants was associated with a decreased risk of harboring a TP53 mutation (OR, 0.50; 95% CI, 0.25-0.96), particularly in patients with tumors in the body and tail of the pancreas (OR, 0.25; 95% CI, 0.07-0.74), Hood says. In total, 51% of patients with BRCA1/2 pathogenic variants had TP53 mutations vs 71% of those in the control group (P = .038). However, investigators observed no significant differences between the arms regarding KRAS mutations (BRCA1/2 arm, 83%; control arm, 86%; P = .60), SMAD4 mutations (16% vs 13%; P = .59), or CDKN2Amutations (19% vs 29%; P = .13), he concludes.