Abstract P2-09-03: Breast cancer prevention: Is it time for population-based mutation screening of high risk genes?

The traditional model of familial breast cancer practice involves ascertaining high-risk individuals based on family history. However, most individuals who carry a BRCA1 or BRCA2 mutation will not have a family history of breast or other cancer in a close relative. Moving germline testing from the familial cancer center to the population will result in many essentially unanticipated findings of great significance in regards to the risk of breast cancer in healthy relatives. To date there have been no large studies that have directly measured the frequency of BRCA1 and BRCA2 mutations in a cancer-free general population. As a first step toward population based BRCA1 or BRCA2 screening, we sequenced the entire coding region of these genes in 1,997 cancer-free Australian women recruited from the lifepool study (www.lifepool.org) which is a cohort of women attending the Australian population based mammographic screening program. Sequencing data were filtered for known pathogenic or novel loss of function mutations. Twelve individuals were identified with pathogenic mutations in either BRCA1 (4 mutations) or BRCA2 (8 mutations), which is consistent with previous indirect estimates for Caucasian populations but to our knowledge this is the largest direct assessment of their prevalence. Interestingly, the self-reported cancer family history of the majority of the 12 mutation positive women was unremarkable. All 12 women subsequently accepted an invitation to attend a Familial Cancer Centre for advice on whether to proceed with formal clinical genetic testing. A population carrier frequency of 0.6% for mutations in BRCA1 and BRCA2, coupled with the rapidly declining costs of gene panel sequencing, suggests that population-based screening for these genes will be a highly cost effective way of reducing the incidence of breast and ovarian cancer through preventative strategies. Citation Format: Campbell IG, Trainer AH, Devereux L, Young M-A, Mitchell G, Rowley S, Li N, James PA, Thompson E. Breast cancer prevention: Is it time for population-based mutation screening of high risk genes?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-03.