Alex B. Blair, Vincent P. Groot, Georgios Gemenetzis, Jishu Wei, John L. Cameron, Matthew J. Weiss, Michael Goggins, Christopher L. Wolfgang, Jun Yu, Jin He
Background: The outcomes of sporadic pancreatic ductal adenocarcinoma (PDAC) patients with germline mutations of BRCA1/BRCA2 remain unclear. The prognostic significance of BRCA1/BRCA2 mutations on survival is not well established.
Methods: We performed targeted next-generation sequencing (NGS) to identify BRCA1/BRCA2 germline mutations in resected sporadic PDAC cases from 2000 to 2015. Germline BRCA mutation-carriers were matched by age and tumor location to those with BRCA1/BRCA2 wild-type genes from our institutional database. Demographics, clinicopathologic features, overall survival (OS) and disease-free survival (DFS) were abstracted from medical records and compared between the two cohorts.
Results: Twenty-two patients with sporadic cancer and BRCA1 (n=4) or BRCA2 (n=18) germline mutations and 105 wild-type patients were identified for this case-control study. BRCA1/BRCA2 mutations were associated with inferior median OS (20.2 vs. 27.8 months, P=0.034) and DFS (8.4 vs. 16.7 months, P<0.001) when compared with the matched wild-type controls. On multivariable analyses a BRCA1/BRCA2 mutation [hazard ratio (HR) =2.10, P<0.001], positive margin status (HR =1.72, P=0.021) and lack of adjuvant therapy (HR =2.38, P<0.001), were all independently associated with worse survival. Within the BRCA1/BRCA2 mutated group, having had platinum-based adjuvant chemotherapy (n=10) was associated with better survival than alternative chemotherapy (n=8) or no adjuvant therapy (n=4) (31.0 vs. 17.8 vs. 9.3 months, P<0.001).
Conclusions: Carriers of BRCA1/BRCA2 mutation with sporadic PDAC had a worse survival after pancreatectomy than their BRCA wild-type counterparts. 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.
