Article Text

Download PDFPDF
Should we offer multi-gene testing to all patients with breast cancer: a cost-effectiveness analysis
  1. L Sun1,2,
  2. A Brentnall3,
  3. S Patel1,2,
  4. D Buist4,
  5. E Bowles4,
  6. DG Evans5,
  7. D Eccles6,
  8. J Hopper7,
  9. S Li7,
  10. S Duffy3,
  11. J Cuzick3,
  12. I dos-Santos-Silva8,
  13. Z Sadique1,
  14. L Yang9,
  15. R Legood1 and
  16. R Manchanda2,10,11
  1. 1Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine
  2. 2Barts Cancer Institute, Queen Mary University of London, UK
  3. 3Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
  4. 4Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
  5. 5Manchester Academic Health Science Centre (MAHSC), Manchester Universities Foundation Trust, St. Mary’s Hospital, The University of Manchester, Manchester
  6. 6Cancer Sciences Academic Unit, Faculty of Medicine and Cancer Sciences, University of Southampton, Southampton, UK
  7. 7Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
  8. 8Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  9. 9School of Public Health, Peking University, Beijing, China
  10. 10Barts Health NHS Trust, Royal London Hospital
  11. 11MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, London, UK

Abstract

Introduction/Background Currently breast cancer (BC) patients are offered genetic-testing only if they have a ≥10% risk of being a BRCA carrier based on family history and clinical criteria. However, this approach misses a large proportion (∼50%) of overall mutation carriers as they fall below this 10% threshold. Mutation identification enables primary prevention for ovarian cancer (OC) in BC-patients and BC-&-OC in unaffected relatives. We estimate incremental lifetime-effects, costs, cost-effectiveness and population impact of multigene-testing all BC patients compared to current practice of family-history/clinical-criteria based genetic (BRCA)-testing.

Methodology Cost-effectiveness microsimulation modelling study comparing lifetime costs-&-effects of 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 and US populations. 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)). The main outcome measure was the incremental cost per quality-adjusted life-year (QALY) gained with a 3.5% annual discount. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses.

Results Compared with current clinical-criteria/family-history-based BRCA-testing, (BRCA1/BRCA2/PALB2) multigene-testing for all BC-patients would cost £10,470/QALY (UK) or $58,702/QALY (US) gained, well below UK/NICE and US cost-effectiveness thresholds of £30,000/QALY & $100,000/QALY. Probabilistic sensitivity-analysis shows unselected multigene-testing remains cost-effective for 98% UK/77% US health-system simulations. One year’s unselected panel-genetic testing can prevent 1,776 BC/OC-cases and 557 deaths in the UK; and 8,258 BC/OC-cases and 2,143 deaths in the US. Correspondingly, 7 UK/32 US excess heart-disease deaths occur annually.

Conclusion Unselected panel genetic-testing for all BC patients compared to current clinical-criteria restricted testing is extremely cost-effective. We recommend changing the current policy to expand genetic testing to all BC patients.

Disclosure RM declares research funding from The Eve Appeal and Cancer Research UK into population testing and from Barts & the London Charity and Rosetree Charity outside this work, as well as an honorarium for grant review from Israel National Institute for Health Policy Research and honorarium for advisory board meeting for MSD and Astrazeneca. DGE declares travel grants paid by Astrazeneca. The other authors declare no conflict of interest.

Statistics from Altmetric.com

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.