Worse Survival for BRCA Germline Mutation Carriers in Pancreatic CA
The BRCA1/BRCA2 mutations correlated with significantly inferior median overall survival and disease-free survival.
HealthDay News — BRCA1/BRCA2 germline mutation carriers with pancreatic ductal adenocarcinoma (PDAC) have worse survival after resection, according to a study published in the Journal of the American College of Surgeons.
Alex B. Blair, M.D., from Johns Hopkins Medical Institutions in Baltimore, and colleagues performed targeted next-generation sequencing to identify BRCA1/BRCA2 germline mutations in resected sporadic PDAC cases from 2000 to 2015.
Germline BRCA mutation carriers (four patients with BRCA1 and 18 with BRCA2) were matched to those with BRCA1/BRCA2 wild-type genes (105 patients). Overall survival (OS) and disease-free survival (DFS) were compared between the cohorts.
The researchers found that, compared with matched wild-type controls, the BRCA1/BRCA2 mutations correlated with significantly inferior median OS (20.2 versus 27.8 months) and DFS (8.4 versus 16.7 months). There were significant independent correlations for BRCA1/BRCA2 mutation, positive margin status, and lack of adjuvant therapy with worse survival in multivariable analysis (hazard ratios, 2.10, 1.72, and 2.38, respectively). Having had platinum-based adjuvant chemotherapy correlated with significantly better survival than alternative chemotherapy or no adjuvant chemotherapy within the BRCA1/BRCA2 mutated group (31.0 versus 17.8 and 9.3 months, respectively).
"Carriers of BRCA1/BRCA2 mutation with sporadic PDAC had a worse survival after pancreatectomy than their BRCA wild-type counterparts," the authors write. "However, platinum-based chemotherapy regimens were associated with markedly improved survival in patients with BRCA1/BRCA2 mutations, with survival differences no longer appreciated with wild-type patients."