title: Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project.
abstract: The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.
authors.affiliation: Air Force Medical Genetics Center, Keesler Air Force Base, MS 39534, USA.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Fries
authors.forename: Charlene
authors.initials: C
authors.lastname: Holt
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carpenter
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Carter
authors.forename: Jamelyn
authors.initials: J
authors.lastname: Daniels
authors.forename: Judith
authors.initials: J
authors.lastname: Flanagan
authors.forename: Kay
authors.initials: K
authors.lastname: Murphy
authors.forename: B Jo
authors.initials: BJ
authors.lastname: Hailey
authors.forename: Laura
authors.initials: L
authors.lastname: Martin
authors.forename: Roderick
authors.initials: R
authors.lastname: Hume
authors.forename: Gracia
authors.initials: G
authors.lastname: Hudson
authors.forename: Mary
authors.initials: M
authors.lastname: Cadman
authors.forename: Ronald
authors.initials: R
authors.lastname: Weatherly
authors.forename: Mark E
authors.initials: ME
authors.lastname: Nunes
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008875:Middle Aged; D008887:Military Medicine; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics