BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high‐risk pancreatic cancer screening and pancreatic cancer cohorts. Issue 13 (15th April 2014)

• Record Type: Journal Article
• Authors: Lucas, Aimee L.; Frado, Laura E.; Hwang, Caroline; Kumar, Sheila; Khanna, Lauren G.; Levinson, Elana J.; Chabot, John A.; Chung, Wendy K.; Frucht, Harold
• Is Part Of: Cancer. Volume 120:Issue 13(2014)
• Page Start: 1960
• Page End: 1967
• Publication Date: 2014-04-15
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28662
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28662-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) is due to a genetic predisposition, including the breast and ovarian cancer syndrome germline mutations <italic>BRCA1</italic> and <italic>BRCA2</italic>. Knowledge of specific genetic mutations predisposing to PDAC may enable risk stratification, early detection, and the development of effective screening and surveillance programs. In the current study, the authors attempted to determine the diagnostic yield of testing for <italic>BRCA1/2</italic> germline mutations in a PDAC screening cohort and a PDAC cohort referred for genetic testing.</p> </sec> <sec id="cncr28662-sec-0002" sec-type="section"> <title>METHODS</title> <p>Patients in a high‐risk PDAC prevention and genetics program or those with a personal history of PDAC who were referred for genetic evaluation underwent testing for <italic>BRCA1/2</italic> germline mutations. Clinical <italic>BRCA1/2</italic> genetic testing included testing for the 3 Ashkenazi Jewish founder mutations or <italic>BRCA1/2</italic> comprehensive testing.</p> </sec> <sec id="cncr28662-sec-0003" sec-type="section"> <title>RESULTS</title> <p>A total of 37 patients without PDAC underwent <italic>BRCA1/2</italic> testing at the study institution. Genetic testing identified 7 patients who were <italic>BRCA1/2</italic> carriers for a yield of 18.9%. Six patients carried Ashkenazi Jewish founder mutations (3 with <italic>BRCA1</italic> and 3 with <italic>BRCA2</italic>), and 1 patient was found to have a <italic>BRCA2</italic> mutation on comprehensive testing. Thirty‐two patients with PDAC underwent <italic>BRCA1/2</italic> genetic testing. Five patients had Ashkenazi Jewish founder mutations (2 with <italic>BRCA1</italic> and 3 with <italic>BRCA2</italic>), and 2 patients were found to have <italic>BRCA2</italic> mutations on comprehensive testing. The diagnostic yield was 7 of 32 patients (21.9%).</p> </sec> <sec id="cncr28662-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p> <italic>BRCA1/2</italic> testing is useful in PDAC risk stratification and alters risk assignment and screening recommendations for mutation‐positive patients and their families. Clinical <italic>BRCA1/2</italic> testing should be considered in patients of Ashkenazi Jewish descent with a personal history or family history of PDAC, even in the absence of a family history of breast and ovarian cancer. <bold><italic>Cancer</italic> 2014;120:1960–1967</bold>. © <italic>2014 American Cancer Society</italic>.</p> </sec> </abstract>