title: Incidence of BRCA1/2 germ line alterations in a high risk cohort participating in a phase II chemoprevention trial.
abstract: It is unknown what proportion of women at high risk for breast cancer, entering phase II chemoprevention trials, have BRCA1/2 alterations, and whether their initial biomarker patterns or response to preventive interventions will differ between carriers and non-carriers. As part of a 6-month phase II chemoprevention trial of diflouromethlyornithine (DFMO), high-risk subjects (family history, prior precancerous breast disease or prior breast cancer), who had random peri-areolar fine needle evidence of epithelial hyperplasia with or without atypia, were offered genetic counselling and testing at the completion of their study participation. 97% of the 119 women eligible for testing underwent BRCA1/2 gene sequencing, 3 declined. 26 (22%) of the 116 women had an alteration in BRCA1/2. Known deleterious mutations were present in 3 (3%), uncertain significance mutations in 19 (16%), and probable polymorphisms in 6 (5%). There does not appear to be a difference in initial biomarker distribution between participants with and without germ line alterations.
authors.affiliation: Division of Clinical Oncology, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160-7418, USA.
authors.forename: J
authors.initials: J
authors.lastname: Klemp
authors.forename: D
authors.initials: D
authors.lastname: Brady
authors.forename: T S
authors.initials: TS
authors.lastname: Frank
authors.forename: B F
authors.initials: BF
authors.lastname: Kimler
authors.forename: C J
authors.initials: CJ
authors.lastname: Fabian
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control; D015331:Cohort Studies; D000518:Eflornithine / Q000627:therapeutic use*; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors; D000518:Eflornithine