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. 2024 Feb 5;7(2):e2355324.
doi: 10.1001/jamanetworkopen.2023.55324.

Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer

Xia Wei  1   2 , Li Sun  1   2 , Eric Slade  3 , Caitlin T Fierheller  2 , Samuel Oxley  2   4 , Ashwin Kalra  2   4 , Jacqueline Sia  2   4 , Michail Sideris  2   4 , W Glenn McCluggage  5 , Nathan Bromham  3 , Katharina Dworzynski  3 , Adam N Rosenthal  6   7 , Adam Brentnall  2 , Stephen Duffy  2 , D Gareth Evans  8 , Li Yang  9 , Rosa Legood  1   2 , Ranjit Manchanda  1   2   4   10
Affiliations

Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer

Xia Wei et al. JAMA Netw Open. .

Abstract

Importance: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed.

Objective: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs.

Design, setting, and participants: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed.

Exposures: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention.

Main outcomes and measures: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated.

Results: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs.

Conclusions and relevance: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Oxley reported receiving grants from Rosetrees Trust outside the submitted work. Dr Brentnall reported receiving royalty payments for commercial use of the Tyrer-Cuzick (IBIS) breast cancer risk evaluation tool from Cancer Research UK outside the submitted work and being a member of a National Institute for Health and Care Excellence committee for guideline development on identifying and managing familial and genetic risk for ovarian cancer. Dr Evans reported receiving personal fees from AstraZeneca and Everythinggenetic outside the submitted work. Dr Yang reported receiving grants from China Medical Board during the conduct of the study and grants from the National Key R&D Program of China and the National Natural Science Foundation of China outside the submitted work. Dr Manchanda reported receiving grants from Rosetrees Trust, Barts Charity, and the China Medical Board during the conduct of the study and receiving grants from Yorkshire Cancer Research, GSK, NHS England, and the NHS Innovation Accelerator; receiving speaking fees from GSK; and receiving personal fees for serving on the advisory boards for EGL and AstraZeneca outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Model Overview
The figure includes the decision tree pathway for choosing eligible surveillance and prevention strategies and the schematic illustration of the health states and key transitions for the Markov model. Model structure and compared strategies are adjusted based on the ovarian cancer (OC) and breast cancer (BC) risk level conferred by pathogenic variants in individual cancer susceptibility genes, ie, BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1. RRM indicates risk-reducing mastectomy; and RRSO, risk-reducing salpingo-oophorectomy.
Figure 2.
Figure 2.. Cost-Effectiveness Acceptability Curves for BRCA1, BRCA2, and PALB2 Pathogenic Variant Carriers
To convert pounds to US dollars, multiply by 1.38. BC indicates breast cancer; QALY, quality-adjusted life year; RRM, risk-reducing mastectomy; RRSO, risk-reducing salpingo-oophorectomy.
See this image and copyright information in PMC

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