@article{discovery10041887,
            year = {2018},
           title = {Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women},
         journal = {Journal of the National Cancer Institute},
           month = {July},
          number = {7},
           pages = {714--725},
          volume = {110},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
             url = {https://doi.org/10.1093/jnci/djx265},
        abstract = {Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women. Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer ({$\ge$}10\% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer. Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = {\pounds}7629.65/QALY or \$49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = {\pounds}21 599.96/QALY or \$54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At {\pounds}30 000/QALY and \$100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7\% and 92.7\% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2\% and 5.8\% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86\%/1.91\% of BC and 3.2\%/4.88\% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million. Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.},
            issn = {1460-2105},
          author = {Manchanda, R and Patel, S and Gordeev, VS and Antoniou, AC and Smith, S and Lee, A and Hopper, JL and MacInnis, RJ and Turnbull, C and Ramus, SJ and Gayther, SA and Pharoah, PDP and Menon, U and Jacobs, I and Legood, R},
        keywords = {mutation, cancer, cost effectiveness, brca1 protein, brca2 protein, brca1 gene, brca2 gene, life expectancy, quality-adjusted life years, mastectomy, breast cancer, brca2 mutation testing, sensitivity analysis, palb2 gene}
}