CLINICAL REPORTClinical outcomes in pancreatic adenocarcinoma associated with BRCA-2 mutationVyas, Ojasa; Leung, Keitha; Ledbetter, Leslieb; Kaley, Kristinc; Rodriguez, Teresad; Garcon, Marie C.d; Saif, Muhammad W.aAuthor Information 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 Correspondence to Muhammad W. Saif, MD, MBBS, Cancers and Experimental Therapeutics, Tufts University School of Medicine, 800 Washington Street, Boston, MA 02111, USA Tel: +1 617 636 5627; fax: +1 617 636 8535; e-mail: [email protected] Received July 17, 2014 Accepted September 5, 2014 Anti-Cancer Drugs: February 2015 - Volume 26 - Issue 2 - p 224-226 doi: 10.1097/CAD.0000000000000178 Buy Metrics 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. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.