title: An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions.
abstract: BACKGROUND
  BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported.
  
  
  METHODS
  Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center.
  
  
  RESULTS
  Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response.
  
  
  CONCLUSIONS
  BRCA mutation-associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Maeve A
authors.initials: MA
authors.lastname: Lowery
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsen
authors.forename: Zsofia K
authors.initials: ZK
authors.lastname: Stadler
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Yu
authors.forename: Yelena Y
authors.initials: YY
authors.lastname: Janjigian
authors.forename: Emmy
authors.initials: E
authors.lastname: Ludwig
authors.forename: David R
authors.initials: DR
authors.lastname: D'Adamo
authors.forename: Erin
authors.initials: E
authors.lastname: Salo-Mullen
authors.forename: Mark E
authors.initials: ME
authors.lastname: Robson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kurtz
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology