title: Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers.
abstract: BACKGROUND
  The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, BRCA1/2 mutation carriers with pancreatic cancer may have distinct biologic outcomes.
  
  
  METHODS
  Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data were collected. Disease-free survival and overall survival (OS) were analysed.
  
  
  RESULTS
  Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33-83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent primary resection. Out of 71 participants, 12 received experimental therapy; one patient had missing data, these 13 cases were excluded from OS analysis. Median OS for 58 patients was 14 months (95% CI 10-23 months). Median OS for patients with stage 1/2 disease has not been reached with 52% still alive at 60 months. Median OS for stage 3/4 was 12 months (95% CI 6-15). Superior OS was observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies (22 vs 9 months; P=0.039).
  
  
  CONCLUSIONS
  Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure.
authors: 1] The Oncology Institute the Chaim Sheba Medical Center, Tel Hashomer, Israel [2] The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: T
authors: T
authors: Golan
authors: 1] Department of Surgery, University Health Network, Toronto, ON, Canada [2] Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
authors: Z S
authors: ZS
authors: Kanji
authors: 1] Department of Oncology, Rambam Health Care Campus, University of Haifa, Haifa, Israel [2] Technion, Faculty of Medicine, Haifa, Israel.
authors: R
authors: R
authors: Epelbaum
authors: 1] Department of Surgery, University Health Network, Toronto, ON, Canada [2] Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
authors: N
authors: N
authors: Devaud
authors: 1] Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel [2] Institute of Human Genetics, Rambam Health Care Campus, University of Haifa, Haifa, Israel.
authors: E
authors: E
authors: Dagan
authors: 1] Department of Surgery, University Health Network, Toronto, ON, Canada [2] Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
authors: S
authors: S
authors: Holter
authors: 1] The Oncology Institute the Chaim Sheba Medical Center, Tel Hashomer, Israel [2] The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: D
authors: D
authors: Aderka
authors: 1] The Oncology Institute the Chaim Sheba Medical Center, Tel Hashomer, Israel [2] The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: S
authors: S
authors: Paluch-Shimon
authors: 1] The Oncology Institute the Chaim Sheba Medical Center, Tel Hashomer, Israel [2] The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: B
authors: B
authors: Kaufman
authors: 1] Technion, Faculty of Medicine, Haifa, Israel [2] Institute of Human Genetics, Rambam Health Care Campus, University of Haifa, Haifa, Israel.
authors: R
authors: R
authors: Gershoni-Baruch
authors: Department of Surgery, University Health Network, Toronto, ON, Canada.
authors: D
authors: D
authors: Hedley
authors: Department of Surgery, University Health Network, Toronto, ON, Canada.
authors: M J
authors: MJ
authors: Moore
authors: 1] The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel [2] The Susanne Levy Gertner Oncogenetics Unit Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors: E
authors: E
authors: Friedman
authors: 1] Department of Surgery, University Health Network, Toronto, ON, Canada [2] Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
authors: S
authors: S
authors: Gallinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015996:Survival Rate
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D005819:Genetic Markers; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin