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

• Published in: European journal of cancer (1990) Vol. 36; no. 10; pp. 1209 - 1214
• Main Authors: Klemp, J, Brady, D, Frank, T.S, Kimler, B.F, Fabian, C.J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2000
• Subjects: Adult; Antineoplastic Agents - therapeutic use; BRCA mutation; BRCA2 gene; BRCA2 Protein; Breast Neoplasms - genetics; Breast Neoplasms - prevention & control; chemoprevention; Cohort Studies; difluromethylornithine; Eflornithine - therapeutic use; Female; Genes, BRCA1 - genetics; Germ-Line Mutation - genetics; Humans; Middle Aged; Neoplasm Proteins - genetics; Pedigree; Prevention trial; Risk Factors; Transcription Factors - genetics; Prevention trial; BRCA mutation
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(00)00112-X

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.