Pancreatic cancer and BRCA mutation in familial breast cancer families.

9550 Background: The majority of individuals presenting to a high-risk cancer clinic have a personal/family history (FHx) of breast cancer. For those individuals who wish to have genetic testing, germ-line sequencing for the familial breast cancer genes BRCA1/2 may help to quantify risk of breast and/or ovarian cancer and may provide guidance regarding screening or prophylaxis. Pancreatic adenocarcinoma (PC) is one of a spectrum of cancers related to BRCA mutation. Recently, BRCA2 has been identified as a major familial PC susceptibility gene. Approximately 5-15% of unselected PC's have germ-line mutations of the BRCA2 gene. While few practitioners currently offer BRCA testing to individuals with a personal/FHx of PC, individuals from hereditary breast/ovarian cancer (HBOC) kindreds who undergo genetic testing may also have a FHx of PC.,From a database of 1411 probands presenting to the University of Chicago Cancer Risk Clinic over the past 10 years, 66 families meeting criteria for HBOC with >1 close (1st or 2nd degree) PC were identified. FHx was obtained by proband proxy and verified by medical records when available. Malignancy history, familial mutation status, and cancers in close relatives were assessed.,Among 66 HBOC kindreds, germ-line testing for BRCA1 and BRCA2 mutations was performed in 31(47%) probands or close relatives. 8BRCA1 and 9BRCA2 mutations were found, as well as 2 families with BRCA2 variants. In total 17/31(55%) families with mutations had a solitary PC in a close relative. One family each with BRCA1 and BRCA2 mutations had two close relatives with PC, and one BRCA2 family contained 4 PC's. Age of PC diagnosis did not correlate with mutation status; however, PC in BRCA2 families had a mean younger age of onset [57.1 yrs, 49.1-64.3] than in BRCA1 [66 yrs, 57.1-74.7].[p=0.12] or families with a negative test [70.0 yrs, 61.2-84.2][p=0.03].,In a high-risk population, BRCA1 and BRCA2 mutations are common among HBOC families with PC in a close relative. FHx of PC, particularly early-onset, may have predictive power in identifying individuals with germ-line BRCA mutations, including BRCA+ familial PC kindreds. No significant financial relationships to disclose.