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J Am Coll Surg. 2018 Apr;226(4):630-637.e1. doi: 10.1016/j.jamcollsurg.2017.12.021. Epub 2018 Jan 5.

BRCA1/BRCA2 Germline Mutation Carriers and Sporadic Pancreatic Ductal Adenocarcinoma.

Author information

1
Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD.
2
Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD.
3
Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD.
4
Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD.
5
Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD. Electronic address: jhe11@jhmi.edu.

Abstract

BACKGROUND:

The outcomes of sporadic pancreatic ductal adenocarcinoma (PDAC) patients with germline mutations of BRCA1/BRCA2 remains unclear. The prognostic significance of BRCA1/BRCA2 mutations on survival is not well established.

STUDY DESIGN:

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 2 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. The 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, respectively, 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.

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PMID:
29309945
PMCID:
PMC6178809
DOI:
10.1016/j.jamcollsurg.2017.12.021
[Indexed for MEDLINE]
Free PMC Article

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