Population-based BRCA1 / BRCA2 testing has been investigated extensively in the Ashkenazi-Jewish (AJ) population and has been shown to have several advantages compared with family history (FH) based testing. FH-based testing requires individuals to fulfil stringent clinical criteria; however, many BRCA1 / BRCA2 carriers do not meet this clinical threshold for genetic testing based on cancer history in the family. This approach results in >50% of additional at-risk carriers being missed by FH-driven clinical criteriaebased testing. Randomized trial data show that population-testing does not impact psychological well-being or quality-of- life detrimentally. There is an overall reduction in anxiety, distress, and uncertainty, although higher levels of cancer-related distress in those women who test positive are reported. Additionally delivery of testing through a population-based model is acceptable, and testing can be delivered in the community outside of hospital-based genetic clinics with high satisfaction rates. Also, the feasibility of population-based genetic testing has been accelerated by the availability of next-generation sequencing and the decreasing costs of genetic testing.
There are significant resource implications to consider around population-based BRCA1/BRCA2 testing. Assessments of the full health economic implications are critical to inform any potential policy change. A health economic assessment allows for the evaluation of the overall costs and benefits for the genetic testing of BRCA1/BRCA2 mutations in women of differing AJ ancestry.
We previously used a decision analytical model to compare the costs and consequences of population-based testing in AJ women who were 30 years old with AJ grandparents. The data used in this model was obtained from the Genetic Cancer Prediction through Population Screening randomized trial (ISRCTN73338115) that compared outcomes of population and FH-based approaches for genetic testing of women with AJ grandparents. The model showed that overall, when the down-stream costs of treatment were taken into account, population-testing was in fact cost-saving compared with FH-testing. The modelling predicted that this could lead to a significant reduction in breast-and-ovarian cancer incidence and increase life expectancy. However, our original analysis applies only to women with 4 AJ grandparents and is not applicable directly to every woman with AJ ancestry because 25% United Kingdom (UK) and 44% United States (US) Jewish marriages are to non-Jews. These women thus may have just 1, 2, or 3 AJ grandparents; therefore, the prevalence of BRCA1 / BRCA2 mutations is lower in these groups. Nevertheless, these women remain at elevated BRCA risk compared with the general (non-Jewish) population. Cost-effectiveness data for these varying lower mutation prevalence levels are unavailable. This important gap in knowledge was highlighted at a recent meeting of experts on population-based AJ BRCA testing in Haifa, Israel, in July 2016.11 We present an updated cost-effectiveness analysis of population BRCA1/BRCA2 testing for women with 1, 2, and 3 AJ grandparents.
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