Cost-effectiveness of population-based BRCA1/2 testing and ovarian cancer prevention for Ashkenazi Jews: A call for dialogue

Abstract

Purpose: About half of unaffected BRCA1/2 carriers have a negative family history, confounding efforts toward presymptomatic carrier identification. Ovarian cancer is preventable for known carriers but is otherwise highly lethal. Cost-effectiveness and gains in life expectancy are important factors in evaluating the desirability of population-based genetic screening, currently the only viable strategy to identify carriers with unrevealing family histories. Methods: Cost-utility analysis for a population-based genetic screening program offered to American Ashkenazi Jewish women aged 35-55 years measuring cancer incidence, life expectancy, and cost. Results: Our model predicts that a genetic screening program would result in 2811 fewer cases of ovarian cancer, with a life expectancy gain of 1.83 quality-adjusted life years among carriers. At a cost of $460 for founder mutation testing, the cost of the program is $8300 (discounted) per year of quality-adjusted life gained. Conclusion:In populations with a high prevalence of BRCA1/2 founder mutations, genetic screening may be cost-effective when compared with recommended public health interventions such as mammographic screening. We advocate the initiation of a dialogue among Jewish stakeholders, genetics professionals, and public health leaders to determine whether a population-based BRCA1/2 genetic screening program should be pursued. Genet Med 2009:11(9):629 -639. Key Words: BRCA1, BRCA2, decision analysis, ovarian carcinoma, population-based genetic screeningA n inherited predisposition to hereditary breast and ovarian cancer should be heralded by a strong cancer family history, but surprisingly often, it is not. Incomplete penetrance, sexlimited expression, limited family structure, and incomplete family history information all contribute to the frequent observation of hereditary cancer cases, which lack premonitory clues. Female BRCA1/2 carriers who are unaware of their genetic status cannot undertake recommended measures such as early mammography and breast magnetic resonance imaging (MRI) or avail themselves of risk-reducing salpingo-oophorectomy after completion of childbearing. Women with nonscreen detected, early-onset breast cancer and those who develop ovarian cancer can be expected to face much higher morbidity and mortality than if they were undergoing high-risk management.An underlying assumption in clinical cancer genetics is that by maximizing the efficiency of the referral pipeline through such means as physician and patient education and computerized family history tools, most unaffected BRCA1/2 carriers could be identified before developing cancer. High-risk management could then be instituted in a family-centered manner to reduce the cancer burden. Although this holds true for families with recognizable features of hereditary cancer, several studies suggest that about half of all BRCA1/2 families cannot be identified using this approach. [1][2][3][4][5][6][7][8] BRCA1/2 mutation prevalence rates have been measured in several population-based...

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

“…16,17 Ancestry-informed testing of a few common BRCA1/2 mutations has been proposed as a cost-effective approach in a number of populations including Ashkenazi Jews. [18][19][20][21][22][23][24][25] Diagnosing BRCA mutations triggers preventive measures in relatives, which contributes to the value of such screening approaches. 21 The identification of a prevalent founder mutation in a very specific part of the Tyrol may facilitate a long-term study to examine the true sensitivity, usefulness, and cost-effectiveness of routine testing of breast or ovarian cancer patients without any selection based on established HBOC criteria.…”

BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening

“…Rubinstein et al 22 demonstrated that population BRCA genetic screening of women of the Ashkenazi Jewish population in the United States between the ages of 35 and 55 years would be cost-effective with regard to surgical prevention and treatment of ovarian cancer. Metcalfe et al 23 reported a significant response to a newspaper advertisement offering general BRCA genetic testing to Jewish women in Ontario, Canada.…”

Population-based BRCA1/BRCA2 screening in Ashkenazi Jews: A call for evidence

“…In 2005, the US Preventive Services Task Force recommended BRCA1/BRCA2 testing only for women with an increased-risk family history, defined in Ashkenazi Jews as any first-degree relative (or two second-degree relatives on the same side of the family) with breast or ovarian cancer. 5 As noted by Rubinstein et al, 1 subsequent studies have shown that approximately half of BRCA1/BRCA2 carriers identified after diagnosis of breast cancer and one third of carriers identified after diagnosis of ovarian cancer do not have significant family history of either cancer.…”

“…As discussed by Rubinstein et al, 1 we have yet to determine the most effective pretest and post-test processes. Pretesting traditional genetic counseling should be compared with other methods, which may be less costly.…”

“…As noted by Rubinstein et al 1 in this issue, BRCA1/BRCA2 testing in the Ashkenazi Jewish population, aimed at reducing morbidity and mortality of breast/ovarian cancer, is seemingly an obvious candidate for such a screening program. In Ashkenazi Jews, three common, easily tested mutations account for the majority of deleterious alleles, effective preventive measures for BRCA1/BRCA2 carriers exist, and this ethnic group has historically embraced genetic testing, albeit carrier screening for recessive disorders.…”