Article Text

Download PDFPDF
443 Cost-effectiveness analysis of cancer susceptibility gene-specific prevention strategies for ovarian and breast cancer
  1. Xia Wei1,
  2. Li Sun1,
  3. Eric Slade2,
  4. Caitlin Fierheller3,
  5. Samuel Oxley3,
  6. Ashwin Kalra3,
  7. Jacqueline Sia3,
  8. Michail Sideris3,
  9. W Glenn Mccluggage4,
  10. Nathan Bromham2,
  11. Katharina Dworzynski2,
  12. Adam N Rosenthal5,
  13. Adam Brentnall3,
  14. Stephen Duffy3,
  15. D Gareth Evans6,
  16. Li Yang7,
  17. Rosa Legood1 and
  18. Ranjit Manchanda3
  1. 1London School of Hygiene and Tropical Medicine, London, UK
  2. 2National Institute for Health and Care Excellence, London, UK
  3. 3Queen Mary University of London, London, UK
  4. 4Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, UK
  5. 5University College London Hospitals NHS Foundation trust, London, UK
  6. 6University of Manchester, Manchester, UK
  7. 7Peking University, Beijing, China


Introduction/Background Risk-reducing surgery, medical prevention, and breast cancer (BC) surveillance offer the opportunity to manage BC and ovarian cancer (OC) risk in BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 cancer-susceptibility-gene (CSG) carriers, but their cost-effectiveness remains poorly addressed. We aimed to estimate the cancers and deaths prevented and cost-effectiveness of eligible prevention and surveillance strategies in BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 CSG-carriers. This analysis was used to inform the NICE guideline on women at high-risk of OC.

Methodology A decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and where relevant risk-reducing mastectomy (RRM) compared with non-surgical interventions (BC-surveillance and medical prevention for increased BC-risk) in BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 PV-carriers. The analysis was conducted from UK health-system payer-perspective, with incremental cost-effectiveness ratio (ICER) calculated as incremental cost per quality-adjusted life-year (QALY) gained. Sensitivity and scenario analyses were performed. OC/BC cases and deaths prevented were estimated.

Results Undergoing both RRSO and RRM was most cost-effective for BRCA1 (RRM: 30-years; RRSO: 35-years), BRCA2 (RRM: 35-years; RRSO: 40-years), PALB2 (RRM: 40-years; RRSO: 45-years) PV-carriers. The corresponding ICERs were £-1,942/QALY, £-89/QALY, £2,381/QALY respectively. RRSO at age 45-years was cost-effective for RAD51C/RAD51D/BRIP1 PV-carriers compared with non-surgical strategies. The corresponding ICERs were £962/QALY, £771/QALY, £2,355/QALY respectively. The most cost-effective preventive strategy per 1000 PV-carriers could prevent 923 OC/BC cases/302 deaths in BRCA1; 686 OC/BC cases/170 deaths in BRCA2; 464 OC/BC cases/130 deaths in PALB2; 102 OC cases/64 deaths in RAD51C; 118 OC cases/76 deaths in RAD51D; and 55 OC cases/37 deaths in BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM was most cost-effective in 96.5%, 89.2%, 84.8% simulations for BRCA1/BRCA2/PALB2, while RRSO was cost-effective in 100% simulations for RAD51C/RAD51D/BRIP1.

Conclusion RRSO with/without RRM at varying respective optimal ages was cost-effective compared with non-surgical strategies for individual BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 PV-carriers. These findings support and enable personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC-risk management.

Disclosures RM reports receiving grants from GSK, NHS Innovation Accelerator (NIA), and Yorkshire Cancer Research outside the submitted work, and honoraria for advisory board membership from Astrazeneca/MSD/GSK/EGL. No other disclosures were reported.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.