title: Clinical outcomes in pancreatic adenocarcinoma associated with BRCA-2 mutation.
abstract: Patients with BRCA-1 and BRCA-2 germ line mutations are at an increased risk of developing pancreatic adenocarcinoma (PAC). In particular, the BRCA-2 mutation has been associated with a relative risk of developing PAC of 3.51. The BRCA-2 protein is involved in repair of double-stranded DNA breaks. Recent reports have suggested that in the setting of impaired DNA repair, chemotherapeutic agents that induce DNA damage, such as platinum-based antineoplastic drugs (platins) and poly(ADP-ribose) polymerase inhibitors (PARP inhibitors), have improved efficacy. However, because of the relative rarity of BRCA-related PAC, studies evaluating such agents in this setting are scarce. Patients with a known BRCA-2 mutation and PAC were retrospectively reviewed. Ten patients with PAC and BRCA-2 mutation were identified. Four patients (40%) were of Ashkenazi Jewish descent. Seven patients (70%) received platinum agents, two (20%) received mitomycin-C, one (10%) received a PARP inhibitor, and seven (70%) received a topoisomerase-I inhibitor. Overall, chemotherapy was well tolerated with expected side effects. Patients with a BRCA-2 mutation and PAC represent a group with a unique biology underlying their cancer. Chemotherapies such as platinum derivatives, mitomycin-C, topoisomerase-I inhibitors, and PARP inhibitors targeting DNA require further investigation in this population. Genetic testing may guide therapy in the future.
authors.affiliation: aTufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts bUniversity of Alabama at Birmingham (UAB), Birmingham, Alabama cYale New Haven Hospital, New Haven, Connecticut dColumbia University Medical Center, New York, New York, USA.
authors.forename: Ojas
authors.initials: O
authors.lastname: Vyas
authors.forename: Keith
authors.initials: K
authors.lastname: Leung
authors.forename: Leslie
authors.initials: L
authors.lastname: Ledbetter
authors.forename: Kristin
authors.initials: K
authors.lastname: Kaley
authors.forename: Teresa
authors.initials: T
authors.lastname: Rodriguez
authors.forename: Marie C
authors.initials: MC
authors.lastname: Garcon
authors.forename: Muhammad W
authors.initials: MW
authors.lastname: Saif
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D024682:BRCA2 Protein / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012189:Retrospective Studies; D059004:Topoisomerase I Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004791:Enzyme Inhibitors; D009944:Organoplatinum Compounds; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D059004:Topoisomerase I Inhibitors; D016685:Mitomycin