Abstract PD1-07: Population genetic testing for breast cancer susceptibility
Authors: Campbell IG , Rowley S , Devereux L , McInerny S , Grewal N , Young M-A , Lee A , Trainer A , James P 
Published: February 2018

Background. Germline mutations in certain genes account for a large proportion of inherited risk for breast and ovarian cancer. The identification of asymptomatic mutation carriers could significantly reduce the incidence of these diseases as active risk management can dramatically reduce the risk of developing cancer.

In most countries, identifying high-risk individuals is based on their family history. In general, a family is first identified because one family member develops cancer and, because of high-risk indicators is referred to a familial cancer centre (FCC). However, current data suggests that many BRCA1 or BRCA2 mutation carriers do not have a remarkable history of cancer in a close relative. Population-based genetic testing would be a far more effective strategy for identification of at-risk individuals. To test the feasibility of such a strategy we are conducting a population genetic testing trial for actionable mutations in 11 breast/ovarian cancer predisposition genes (BRCA1, BRCA2, PALB2, ATM, CDH1, PTEN, STK11, TP53, BRIP1, RAD51C, RAD51D) among 15,000 healthy women from the Australian population.

Methods. All subjects are female participants in the LifePool cohort (www.lifepool.org) who had no personal history of breast or ovarian cancer at the time of DNA collection. Participants found to carry an actionable germline mutation were notified by letter with an invitation to contact the PeterMac telephone genetic counselling service for further information and/or also invited for counselling at an FCC. Only participants with an actionable mutation were notified of their genetic testing result.

Results. Of the 5,557 women tested to date, 40 (0.72%) were carriers of mutations that are currently actionable in the Australian context (BRCA1 n=7, BRCA2 n=15, PALB2 n=15, ATM n=3). All 40 women accepted the invitation to attend a familial cancer centre for formal predictive testing. Less than 20% of the women would have met the minimum threshold for clinical genetic testing under current guidelines. A further 16 participants (0.29%) carried mutations in BRIP1, RAD51C and RAD51D but were not notified of the result as these genes are not currently actionable in Australia. No mutations were identified in CDH1, PTEN, STK11 or TP53.

Conclusions. A relatively large proportion of cancer free-women from Australia carry high-risk mutations in BRCA genes and subsequent uptake of clinical genetic testing was very high. Population-based genetic testing is well accepted and can identify a much larger proportion of the at risk-population than contemporary family history based approaches.

Citation Format: Campbell IG, Rowley S, Devereux L, McInerny S, Grewal N, Young M-A, Lee A, Trainer A, James P. Population genetic testing for breast cancer susceptibility [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD1-07.