Clinical outcomes in pancreatic adenocarcinoma associated with BRCA-2 mutation. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Vyas, Ojas; Leung, Keith; Ledbetter, Leslie; Kaley, Kristin; Rodriguez, Teresa; Garcon, Marie C.; Saif, Muhammad W.
• Is Part Of: Anti-cancer drugs. Volume 26:Issue 2(2015)
• Publication Date: 2015-02
• Subjects: Antineoplastic agents -- Periodicals; Cancer -- Chemotherapy -- Periodicals; Antineoplastic Agents -- therapeutic use -- Periodicals; Drug Therapy -- Periodicals; 616.994061
• DOI: 10.1097/CAD.0000000000000178
• Languages: English
• ISSNs: 0959-4973

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>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.</p> </sec> </abstract>