Population-based genetic testing of 16,000 healthy Australian women for germline mutations in hereditary breast and ovarian cancer predisposition genes


Session type:

Ian Campbell1,Lisa Devereux1,Simone Rowley1,Na Li1,Alison Trainer1,Paul James1
1Peter MacCallum Cancer Centre



The identification of carriers of actionable mutations in hereditary breast and ovarian cancer genes through family cancer history alone is suboptimal particularly since over 50% of germline mutation carriers report no significant family history. Population-based genetic testing of the asymptomatic population has the potential to lower the incidence of breast and ovarian cancer incidence compared to a family history-based testing approach. We are conducting population-based genetic testing of HBOC genes in 16,000 cancer-free unselected women from the Australian population with the  aim of determining the prevalence of pathogenic mutations and assess the rate of uptake of genetic counselling, risk reduction surgery and cascade testing following notification of a potential clinically relevant finding.


Germline DNA from 16,000 healthy Australian women participating in the lifepool project (www.lifepool.org) is being screened using an 11-gene custom sequencing panel. Women with clinically actionable results are invited to attend a familial cancer clinic for post-test genetic counselling and confirmatory testing. Outcomes measured included the prevalence of pathogenic variants, and the uptake rate of genetic counselling, risk reduction surgery, and cascade testing.


The target of 16,000 women will be completed by mid 2019 and to date, 38 of 5910 women (0.64%) carried a clinically actionable mutation (BRCA1, BRCA2, PALB2, ATM). 42% of mutation carriers did not have a first degree relative with breast or ovarian cancer, and 91% accepted referral to an FCC. Uptake of cascade testing and risk reduction surgery was similar to those families identified in standard clinical practice.


Genetic testing was well accepted, and the majority of high-risk gene carriers identified would not meet eligibility criteria for genetic testing based on their existing family history. The findings indicate the clinical utility of identifying a mutation in this setting and outcomes are in keeping with those reported with the current model of clinical practice.