Incidence of BRCA1/2 germ line alterations in a high risk cohort participating in a phase II chemoprevention trial

It is unknown what proportion of women at high risk for breast cancer, ente ring phase II chemoprevention trials, have BRCA1/2 alterations, and whether their initial biomarker patterns or response to preventive interventions w ill differ between carriers and noncarriers. As part of a 6-month phase II chemoprevention trial of diflouromethylornithine (DFMO), high-risk subjects (family history, prior precancerous breast disease or prior breast cancer) , who had random peri-areolar fine needle evidence of epithelial hyperplasi a with or without atypia, were offered genetic counselling and testing at t he completion of their study participation. 97% of the 119 women eligible f or testing underwent BRCA1/2 gene sequencing, 3 declined. 26 (22%) of the 1 16 women had an alteration in BRCA 1/2. Known deleterious mutations were pr esent in 3 (3%), uncertain significance mutations in 19 (16%), and probable polymorphisms in 6 (5%). There does not appear to be a difference in initi al biomarker distribution between participants with and without germ line a lterations. (C) 2000 Elsevier Science Ltd. All rights reserved.