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Prevalence of Germline BRCA Mutations 5% in Patients With Pancreatic Adenocarcinoma
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Nearly 5% of patients with pancreatic ductal adenocarcinoma harbored a germline BRCA1 or BRCA2 mutation, according to study results.
Patients with an Ashkenazi Jewish ancestry were significantly more likely to harbor a germline BRCA mutation, results also showed.
Germline BRCA1/2 mutations have been associated with an increased risk for pancreatic ductal adenocarcinoma, but data on the prevalence of BRCA1 mutations in these patients are lacking, according to study background. Identification of BRCA mutations in these patients may have important implications for treatment options.
Steven Gallinger
Steven Gallinger, MD, MSc, FRCS, of the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, and colleagues determined the frequency of BRCA1/2 mutations in 306 patients with incident pancreatic ductal adenocarcinoma. Fifty-one percent of the population was male and the mean age at presentation was 66 years. Thirty-three patients (10.8%) had Ashkenazi Jewish ancestry.
Researchers used Sanger sequencing and multiplex ligation-dependent probe amplification to analyze patients’ DNA for BRCA1 and BRCA2 germline mutations.
Fourteen patients (4.6%) harbored germline BRCA mutations, most of which were BRCA2 (3.6%). Twelve percent of the Ashkenazi Jewish population harbored a BRCA mutation compared with 3.7% of the non-Ashkenazi population (P = .05).
Researchers then categorized patients’ family history of cancer characteristics based on the Ontario Ministry of Health and Long-Term Care (MOHLTC) BRCA1 and BRCA2 genetic testing criteria and the National Comprehensive Cancer Network Hereditary Breast and/or Ovarian Cancer Testing Criteria. Meeting these criteria was significantly linked to mutation carrier status (MOHLTC, P < .001; NCCN, P = .02).
However, a majority of patients with BRCA mutations did not have a family history typical of hereditary breast or ovarian cancers. Fifty-seven percent of patients with BRCA mutations did not meet NCCN criteria and 64% did not meet MOHLTC criteria for testing.
Having a personal history or a family history of cancer each neared statistical significance for BRCA mutation carrier status. Five patients with BRCA mutations had a personal history of cancer; however, three of these patients were diagnosed with cancers that were not typical of hereditary breast or ovarian cancers. A family history of pancreatic ductal adenocarcinoma was not a significant predictor for mutation carrier status; however, 12.1% of the study population had a first-, second- or third-degree relative with pancreatic ductal adenocarcinoma.
“Because the majority of our BRCA mutation carriers did not have a family history consistent with hereditary breast/ovarian cancer, it is difficult for health care providers to determine which patients are likely to carry a mutation,” Gallinger and colleagues concluded. “We recommend that all Ashkenazi Jewish patients with pancreatic ductal adenocarcinoma and all non–Ashkenazi Jewish patients with pancreatic ductal adenocarcinoma with one or more first- or second-degree relatives with breast or ovarian cancer be offered genetic testing for BRCA1 or BRCA2. Given the high mortality rate of pancreatic ductal adenocarcinoma, ideally patients should be offered genetic counseling and testing at the time of diagnosis because identification of mutation may help tailor treatment.” – by Cameron Kelsall
Disclosure: One researcher reports honoraria from Celgene and consulting roles with Celgene and Incyte.
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