Cost-effectiveness of Population-Wide Genomic Screening for Hereditary Breast and Ovarian Cancer in the United States

This decision analysis estimates the lifetime incremental incidence of hereditary breast and ovarian cancer and the quality-adjusted life-years, costs, and cost-effectiveness of hereditary breast and ovarian cancer genomic screening in an unselected population vs family history-based testing. Question Is it cost-effective to implement population-wide genomic screening for hereditary breast and ovarian cancer (HBOC)? Findings This decision analytical model study found that genomic screening for HBOC among unselected women may be cost-effective depending on the age distribution of the women screened. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value. Meaning Population-level genomic screening for HBOC targeting women aged 20 to 35 years could be considered in settings in which the outcomes of screening can be evaluated, particularly to avoid a reduction in mammography screening among patients with negative test results. Importance Genomic screening for hereditary breast and ovarian cancer (HBOC) in unselected women offers an opportunity to prevent cancer morbidity and mortality, but the potential clinical impact and cost-effectiveness of such screening have not been well studied. Objective To estimate the lifetime incremental incidence of HBOC and the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of HBOC genomic screening in an unselected population vs family history-based testing. Design, Setting, and Participants In this study conducted from October 27, 2017, to May 3, 2020, a decision analytic Markov model was developed that included health states for precancer, for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), for earlier- and later-stage HBOC, after cancer, and for death. A complimentary cascade testing module was also developed to estimate outcomes in first-degree relatives. Age-specific RRM and RRSO uptake probabilities were estimated from the Geisinger MyCode Community Health Initiative and published sources. Parameters including RRM and RRSO effectiveness, variant-specific cancer risk, costs, and utilities were derived from published sources. Sensitivity and scenario analyses were conducted to evaluate model assumptions and uncertainty. Main Outcomes and Measures Lifetime cancer incidence, QALYs, life-years, and direct medical costs for genomic screening in an unselected population vs family history-based testing only were calculated. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in cost between strategies divided by the difference in QALYs between strategies. Earlier-stage and later-stage cancer cases prevented and total cancer cases prevented were also calculated. Results The model found that population screening of 30-year-old women was associated with 75 (95% credible range [CR], 60-90) fewer overall cancer cases and 288 QALYs (95% CR, 212-373 QALYs) gained per 100x202f;000 women screened, at an incremental cost of $25 million (95% CR, $21 millon to $30 million) vs family history-based testing; the ICER was $87x202f;700 (78% probability of being cost-effective at a threshold of $100x202f;000 per QALY). In contrast, population screening of 45-year-old women was associated with 24 (95% CR, 18-29) fewer cancer cases and 97 QALYs (95% CR, 66-130 QALYs) gained per 100x202f;000 women screened, at an incremental cost of $26 million (95% CR, $22 million to $30 million); the ICER was $268x202f;200 (0% probability of being cost-effective at a threshold of $100x202f;000 per QALY). A scenario analysis without cascade testing increased the ICER to $92x202f;600 for 30-year-old women and $354x202f;500 for 45-year-old women. A scenario analysis assuming a 5% absolute decrease in mammography screening in women without a variant was associated with the potential for net harm (-90 QALYs per 100x202f;000 women screened; 95% CR, -180 to 10 QALYs). Conclusions and Relevance The results of this study suggest that population HBOC screening may be cost-effective among younger women but not among older women. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value. The potential for harm conferred by inappropriate reduction in mammography among noncarriers should be quantified.