AB003. S003. BRCA1/BRCA2 germline mutation carriers and sporadic pancreatic adenocarcinoma
Abstract

AB003. S003. BRCA1/BRCA2 germline mutation carriers and sporadic pancreatic adenocarcinoma

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

Johns Hopkins University School of Medicine, Baltimore, MD, USA


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.


doi: 10.21037/apc.2018.AB003


Cite this article as: Blair AB, Groot VP, Gemenetzis G, Wei J, Cameron JL, Weiss MJ, Goggins M, Wolfgang CL, Yu J, He J. BRCA1/BRCA2 germline mutation carriers and sporadic pancreatic adenocarcinoma. Ann Pancreat Cancer 2018;1:AB003. doi: 10.21037/apc.2018.AB003

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