TY  - JOUR
VL  - 110
SP  - 714
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
IS  - 7
SN  - 1460-2105
UR  - https://doi.org/10.1093/jnci/djx265
JF  - Journal of the National Cancer Institute
A1  - Manchanda, R
A1  - Patel, S
A1  - Gordeev, VS
A1  - Antoniou, AC
A1  - Smith, S
A1  - Lee, A
A1  - Hopper, JL
A1  - MacInnis, RJ
A1  - Turnbull, C
A1  - Ramus, SJ
A1  - Gayther, SA
A1  - Pharoah, PDP
A1  - Menon, U
A1  - Jacobs, I
A1  - Legood, R
TI  - Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women
EP  - 725
AV  - public
Y1  - 2018/07//
ID  - discovery10041887
N2  - 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 (?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 = £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 = £21 599.96/QALY or $54?769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £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.
KW  - mutation
KW  -  cancer
KW  -  cost effectiveness
KW  -  brca1 protein
KW  -  brca2 protein
KW  -  brca1 gene
KW  -  brca2 gene
KW  -  life expectancy
KW  -  quality-adjusted life years
KW  -  mastectomy
KW  -  breast cancer
KW  -  brca2 mutation testing
KW  -  sensitivity analysis
KW  -  palb2 gene
ER  -