Pashayan, N; Morris, S; Gilbert, F; Pharoah, P; (2018) Cost-effectiveness and Benefit-to-Harm Ratio of Risk-Stratified Screening for Breast Cancer: A Life-Table Model. JAMA Oncology , 4 (11) pp. 1504-1510. 10.1001/jamaoncol.2018.1901.

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Abstract

Importance: The age-based or the ‘one-size-fits-all’ screening approach does not take into account the individual variation in risk. Mammography screening reduces death from breast cancer at a cost of overdiagnosis. Identifying risk-stratified screening strategies with more favourable ratio of overdiagnoses to breast cancer deaths prevented would improve quality of life of women and save resources. / Objective: To assess the benefit to harm balance and the cost-effectiveness of risk-stratified breast screening programmes compared with standard age-based screening programme and no screening. / Design: A life table model using findings of the Independent UK Panel on Breast Cancer Screening and risk distribution based on polygenic risk profile. Setting United Kingdom. The analysis was from the National Health Service perspective. Population and interventions Hypothetical cohort of 365,400 women aged 50 years followed-up to age 85. The interventions were no screening, age-based screening (mammography screening every three years from age 50-69 years), and risk-stratified screening (a proportion of women aged 50 with a risk score greater than a threshold risk were offered screening every three years until age 69) considering each percentile of the risk distribution. / Main outcome measures: Overdiagnoses, breast cancer deaths averted, quality adjusted life years (QALYs) gained, costs, and net monetary benefit (NMB). Probabilistic sensitivity analyses assessed uncertainty around parameter estimates. Future costs and benefits were discounted at 3.5% per year. / Results: In risk-stratified screening, compared to no screening, as the risk threshold was lowered, the incremental cost of the programme increased linearly with no additional QALYs gained below 35th percentile risk threshold. Of the screening scenarios – no screening, age-based, and risk-stratified - the scenario with risk threshold at the 70th percentile had the highest NMB at willingness to pay of £20,000 per QALY gained, with a 72% probability of being cost-effective. Compared with age-based screening, 4 risk-targeted screening at 32nd vs. 70th percentile risk threshold would cost £20,066 vs. £537,985 less, have 9.6% vs. 71% fewer overdiagnoses while averting 2.9% vs. 9.6% fewer breast cancer deaths, respectively. / Conclusion: Not offering screening to women at lower risk would improve the cost-effectiveness of the screening programme, reduce overdiagnosis while maintaining the benefits of screening.

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