Importance: Moving to multigene testing for ‘all’ women with breast cancer (BC) could identify many more mutation carriers who can benefit from precision prevention. However, cost-effectiveness of this approach remains unaddressed.
Objectives: To estimate incremental lifetime-effects, costs, and cost-effectiveness of multigene-testing all BC-patients compared with current practice of family-history/clinical-criteria based genetic (BRCA)-testing.
Design: Cost-effectiveness microsimulation modelling study comparing lifetime costs-&-effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing all unselected BC-cases (Strategy-A) with family-history/clinical-criteria based BRCA1/BRCA2-testing (Strategy-B) in both UK-&-US populations. The time-horizon is lifetime and both payer and societal perspectives are presented. Probabilistic and one-way sensitivity-analyses evaluate model uncertainty.
Setting: Population of UK-&-US women with BC and their relatives
Participants: Data obtained from 11,836 population-based BC-patients (regardless of family-history) recruited to four large research studies in the UK (Predicting-Risk-of-Breast-Cancer-at-Screening (PROCAS: 1389 out of 57,000 women) & Prospective-Outcomes-in-Sporadic-versus-Hereditary-breast-cancer (POSH:2885) studies); US (Kaiser-Permanente Washington Breast-Cancer-Surveillance-Consortium (BCSC) registry: 5892 out of 132,139 women) and Australia (Population-based BC-cases of the Australian-Breast-Cancer-Family-Study (ABCFS:1670 women)).
Interventions: Strategy-A: All BC-women undergo BRCA1/BRCA2/PALB2 testing. Strategy-B: Only BC-women fulfilling family-history/clinical-criteria (10% BRCA-probability) undergo BRCA-testing. Affected BRCA/PALB2-carriers can undertake contralateral preventive-mastectomy. BRCA-carriers can choose risk-reducing salpingo-oophorectomy (RRSO). Relatives of mutation-carriers undergo cascade-testing. Unaffected relative-carriers can undergo MRI/mammography, chemoprevention or risk-reducing-mastectomy for BC-risk and RRSO for ovarian-cancer (OC)-risk.
Main Outcomes & Measures: Incremental-cost-effectiveness-ratio (ICER): incremental-cost per quality-adjusted-life-year (QALY) gained, is compared to standard £30,000/QALY(UK) and $100,000/QALY(US) thresholds. OC-incidence, BC-incidence, excess heart-disease deaths and overall population-impact are estimated.
Results: Compared with current clinical-criteria/family-history-based BRCA-testing, (BRCA1/BRCA2/PALB2) multigene-testing for all BC-patients would cost £10,464/QALY (payer-perspective) or £7,216/QALY (societal-perspective) in UK or $65,661/QALY (payer-perspective) or $61,618/QALY (societal-perspective) in US women, well below UK/NICE and US cost-effectiveness thresholds. Probabilistic sensitivity-analysis shows unselected multigene-testing remains cost-effective for 98-99% UK/ 64-68% US health-system simulations. One year’s unselected multi-gene testing could prevent 2,101 BC/OC-cases and 633 deaths in the UK; and 9,733 BC/OC-cases and 2,406 deaths in the US. Correspondingly, 8 UK/35 US excess heart-disease deaths occur annually.
Conclusions: Unselected high-risk multigene-testing for all BC-patients is extremely cost-effective compared with family-history/clinical-criteria testing for UK and US health-systems. This supports changing current policy to expand genetic-testing to all women with BC.