Population-based approach(es) to genetic testing for ovarian cancer prevention


The landscape in cancer genetics is changing. The traditional family history (FH) based approach to genetic testing implemented through cancer genetic clinics following intensive face-to-face genetic counselling misses >50% mutation carriers and is being replaced by population-based approaches. A randomised trial (GCaPPS;ISRCTN73338115) of BRCA1/2 testing in the Ashkenazi-Jewish (AJ) population comparing population screening (PS) with standard FH-based testing found no difference in psychological/quality of life consequences between the two approaches. Additionally 60% mutations would be missed by FH-criteria alone. A cost-effectiveness analysis suggests that population screening for BRCA1/BRCA2 mutations in AJ women >30years reduces breast/ovarian cancer(OC) incidence by 0.34%/ 0.62%, saves 0.101 quality-adjusted-life-years (QALYs) leading to 33 days gain in lifeexpectancy and is extremely cost-effective with a discounted incremental cost-effectiveness ratio (ICER) of ‘-£2079/QALY.’ 94% of simulations on probabilistic-sensitivity analysis reconfirm population screening is highly cost-effective at £20,000/QALY threshold. This supports a call to change the clinical paradigm in the AJ population. Efficient, acceptable and more cost-effective ways of counselling/delivering genetic risk information on a population basis are necessary for population testing. A cluster-randomised non-inferiority trial shows that DVD-based approach is an effective, acceptable, non-inferior, time saving and cost-efficient alternative to traditional face-to-face genetic counselling in population testing. Telephone counselling is non-inferior in high-risk women. Alternate models like mainstreaming/use of dedicated nurse specialists are being explored in affected individuals. A population-based case series approach for BRCA1/2 testing is recommended for OC. However, implementation is prevented by lack of funding and awareness. Emergence of improved/sophisticated OC-risk models and validated estimates for new moderate penetrance genes (RAD51C/RAD51D/BRIP1) provides opportunity for population risk stratification and will lead to panel testing. The OC-risk threshold for effective surgical prevention is changing and will facilitate a clinical prevention strategy for moderate-risk women. Advances in high-throughput genetic testing technology, computational analytics and systems medicine approach, provides increasing potential for population testing, risk stratification and cancer prevention. Implementation studies assessing acceptability, clinical validity and cost-effectiveness are needed. Competing interests Investigator on the GCaPPS trial on population based testing Research funding from The Eve Appeal for research into population based testing.