Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer

Authors:
Ranjit Manchanda Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, London, UK
Department of Gynecology, All India Institute of Medical Sciences, New Delhi, India

Search for other papers by Ranjit Manchanda in
Current site
Google Scholar
PubMed
Close
 PhD
,
Li Sun Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK

Search for other papers by Li Sun in
Current site
Google Scholar
PubMed
Close
 PhD
,
Monika Sobocan Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK
Division of Gynecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia

Search for other papers by Monika Sobocan in
Current site
Google Scholar
PubMed
Close
 MD
,
Isabel V. Rodriguez Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA

Search for other papers by Isabel V. Rodriguez in
Current site
Google Scholar
PubMed
Close
 PhD
,
Xia Wei Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK

Search for other papers by Xia Wei in
Current site
Google Scholar
PubMed
Close
 MSc
,
Ashwin Kalra Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

Search for other papers by Ashwin Kalra in
Current site
Google Scholar
PubMed
Close
 MBBS
,
Samuel Oxley Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

Search for other papers by Samuel Oxley in
Current site
Google Scholar
PubMed
Close
 MRCOG
,
Michail Sideris Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

Search for other papers by Michail Sideris in
Current site
Google Scholar
PubMed
Close
 PhD
,
Caitlin T. Fierheller Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

Search for other papers by Caitlin T. Fierheller in
Current site
Google Scholar
PubMed
Close
 PhD
,
Robert D. Morgan Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK

Search for other papers by Robert D. Morgan in
Current site
Google Scholar
PubMed
Close
 PhD
,
Dhivya Chandrasekaran Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK

Search for other papers by Dhivya Chandrasekaran in
Current site
Google Scholar
PubMed
Close
 MRCOG
,
Kelly Rust Institute of Genetics and Cancer, Cancer Research UK Edinburgh Centre, University of Edinburgh, Scotland, UK

Search for other papers by Kelly Rust in
Current site
Google Scholar
PubMed
Close
 PhD
,
Pavlina Spiliopoulou School of Cancer Sciences, University of Glasgow, Scotland, UK

Search for other papers by Pavlina Spiliopoulou in
Current site
Google Scholar
PubMed
Close
 PhD
,
Rowan E. Miller Department of Medical Oncology, Barts Health NHS Trust, London, UK

Search for other papers by Rowan E. Miller in
Current site
Google Scholar
PubMed
Close
 PhD
,
Shanthini M. Crusz Department of Medical Oncology, Barts Health NHS Trust, London, UK

Search for other papers by Shanthini M. Crusz in
Current site
Google Scholar
PubMed
Close
 MRCP
,
Michelle Lockley Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK

Search for other papers by Michelle Lockley in
Current site
Google Scholar
PubMed
Close
 PhD
,
Naveena Singh Department of Pathology, Barts Health NHS Trust, London, UK

Search for other papers by Naveena Singh in
Current site
Google Scholar
PubMed
Close
 PhD
,
Asma Faruqi Department of Pathology, Barts Health NHS Trust, London, UK

Search for other papers by Asma Faruqi in
Current site
Google Scholar
PubMed
Close
 FRCP
,
Laura Casey Department of Pathology, Barts Health NHS Trust, London, UK

Search for other papers by Laura Casey in
Current site
Google Scholar
PubMed
Close
 MRCP
,
Elly Brockbank Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

Search for other papers by Elly Brockbank in
Current site
Google Scholar
PubMed
Close
 MRCOG
,
Saurabh Phadnis Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

Search for other papers by Saurabh Phadnis in
Current site
Google Scholar
PubMed
Close
 MRCOG
,
Tina Mills-Baldock Department of Medical Oncology, Barking, Havering, and Redbridge University Hospitals, Essex, UK

Search for other papers by Tina Mills-Baldock in
Current site
Google Scholar
PubMed
Close
 MSc
,
Fatima El-Khouly Department of Medical Oncology, Barking, Havering, and Redbridge University Hospitals, Essex, UK

Search for other papers by Fatima El-Khouly in
Current site
Google Scholar
PubMed
Close
 MRCP
,
Lucy A. Jenkins North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK

Search for other papers by Lucy A. Jenkins in
Current site
Google Scholar
PubMed
Close
 PhD
,
Andrew Wallace Manchester Centre for Genomic Medicine, Division of Evolution, Infection, and Genomic Sciences, University of Manchester, Manchester, UK

Search for other papers by Andrew Wallace in
Current site
Google Scholar
PubMed
Close
 PhD
,
Munaza Ahmed North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK

Search for other papers by Munaza Ahmed in
Current site
Google Scholar
PubMed
Close
 PhD
,
Ajith Kumar North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK

Search for other papers by Ajith Kumar in
Current site
Google Scholar
PubMed
Close
 MRCP
,
Elizabeth M. Swisher Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA

Search for other papers by Elizabeth M. Swisher in
Current site
Google Scholar
PubMed
Close
 MD
,
Charlie Gourley Institute of Genetics and Cancer, Cancer Research UK Edinburgh Centre, University of Edinburgh, Scotland, UK

Search for other papers by Charlie Gourley in
Current site
Google Scholar
PubMed
Close
 PhD
,
Barbara M. Norquist Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA

Search for other papers by Barbara M. Norquist in
Current site
Google Scholar
PubMed
Close
 PhD
,
D. Gareth Evans Manchester Centre for Genomic Medicine, Division of Evolution, Infection, and Genomic Sciences, University of Manchester, Manchester, UK

Search for other papers by D. Gareth Evans in
Current site
Google Scholar
PubMed
Close
 PhD
, and
Rosa Legood Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK

Search for other papers by Rosa Legood in
Current site
Google Scholar
PubMed
Close
 PhD
Restricted access

Background: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)–based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. Methods: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. Results: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year’s testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. Conclusions: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Submitted September 30, 2022; final revision received November 25, 2023; accepted for publication December 18, 2023. Published online April 18, 2024.

These authors contributed equally to this study.

Author contributions: Concept and design: Manchanda, Legood. Model development: Manchanda, Sun, Legood. Patient management: Manchanda, Rodriguez, Kumar, Morgan, Chandrasekaran, Miller, Crusz, Singh, Faruqi, Casey, Brockbank, Phadnis, El-Khouly, Ahmed, Swisher, Gourley, Norquist, Evans. Genetic testing: Jenkins, Wallace. Data acquisition: Manchanda, Sobocan, Rodriguez, Morgan, Chandrasekaran, Rust, Spiliopoulou, Miller, Mills-Baldock, Swisher, Gourley, Norquist, Evans. Statistical/Data analysis: Manchanda, Sun, Legood. Data interpretation: All authors. Funding acquisition: Manchanda. Project administration: Manchanda, Sun, Sobocan, Wei, Kalra, Oxley, Sideris, Chandrasekaran, Lockley, Mills-Baldock. Supervision: Manchanda, Legood. Writing—original draft: Manchanda, Sun, Wei, Legood. Critical revision of the manuscript for important intellectual content and final approval: All authors.

Disclosures: Dr. Manchanda has disclosed receiving honoraria from the Israel National Institute for Health Policy Research, AstraZeneca, MSD, GSK, and EGL Genetics; receiving research support from GSK; serving as an advisory board member for GSK, Everything Genetic Ltd, and AstraZeneca; serving on a speakers’ bureau for GSK; and serving as a consultant for GSK and Everything Genetic Ltd. Dr. Miller has disclosed serving on an advisory board for GSK; and serving on a speaker’s bureau for GSK, AstraZeneca, and Merck & Co., Inc. Dr. Gourley has disclosed receiving research support from AstraZeneca, MSD, and GSK; and serving as a scientific advisor for AstraZeneca. Dr. Evans has disclosed receiving grant/research support from the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This study was funded by the Barts Charity (ECMG1B6R; R. Manchanda) and the Rosetrees Trust (R. Manchanda). Dr. Norquist has disclosed receiving grant/research support from the Department of Defense (DOD) funding grant OC180282.

Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2023.7331. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.

Correspondence: Ranjit Manchanda, PhD, Wolfson Institute of Population Health, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Email: r.manchanda@qmul.ac.uk

View associated content

Supplementary Materials

    • Supplemental Materials (PDF 2.43 MB)
  • Collapse
  • Expand
  • 1.

    International Agency for Research on Cancer. Cancer tomorrow. Accessed January 20, 2019. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/25-ovary-fact-sheet.pdf

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Cheung A, Shah S, Parker J, et al. Non-epithelial ovarian cancers: how much do we really know? Int J Environ Res Public Health 2022;19:1106.

  • 3.

    Zhang S, Royer R, Li S, et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol 2011;121:353357.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Chandrasekaran D, Sobocan M, Blyuss O, et al. Implementation of multigene germline and parallel somatic genetic testing in epithelial ovarian cancer: SIGNPOST study. Cancers (Basel) 2021;13:4344.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Norquist BM, Harrell MI, Brady MF, et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol 2016;2:482490.

  • 6.

    Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017;317:24022416.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 2014;15:852861.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379:24952505.

  • 9.

    Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:19491961.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017;18:12741284.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Schettini F, Giudici F, Bernocchi O, et al. Poly (ADP-ribose) polymerase inhibitors in solid tumours: systematic review and meta-analysis. Eur J Cancer 2021;149:134152.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2021;22:17211731.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    DiSilvestro P, Banerjee S, Colombo N, et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1/GOG 3004 trial. J Clin Oncol 2023;41:609617.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    National Institute for Health and Care Excellence. Olaparib for maintenance treatment of BRCA mutation-positive advanced ovarian, fallopian tube or peritoneal cancer after response to first-line platinum-based chemotherapy. Accessed September 25, 2019. Available at: https://www.nice.org.uk/guidance/ta598/evidence

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    George A, Riddell D, Seal S, et al. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. Sci Rep 2016;6:29506.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Møller P, Hagen AI, Apold J, et al. Genetic epidemiology of BRCA mutations—family history detects less than 50% of the mutation carriers. Eur J Cancer 2007;43:17131717.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Alsop K, Fereday S, Meldrum C, et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 2012;30:26542663.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    NHS England. Clinical commissioning policy: genetic testing for BRCA1 and BRCA2 mutations. Accessed May 1, 2015. Available at: https://www.engage.england.nhs.uk/consultation/specialised-services-consultation/user_uploads/brca-policy.pdf

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Konstantinopoulos PA, Norquist B, Lacchetti C, et al. Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline. J Clin Oncol 2020;38:12221245.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Miller RE, Leary A, Scott CL, et al. ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer. Ann Oncol 2020;31:16061622.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Sundar S, Manchanda R, Gourley C, et al. British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for germline and tumor testing for BRCA1/2 variants in ovarian cancer in the United Kingdom. Int J Gynecol Cancer 2021;31:272278.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Ramus SJ, Song H, Dicks E, et al. Germline mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer. J Natl Cancer Inst 2015;107:djv214.

  • 23.

    Yang X, Song H, Leslie G, et al. Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D. J Natl Cancer Inst 2020;112:12421250.

  • 24.

    Manchanda R, Legood R, Antoniou AC, et al. Specifying the ovarian cancer risk threshold of ‘premenopausal risk-reducing salpingo- oophorectomy’ for ovarian cancer prevention: a cost-effectiveness analysis. J Med Genet 2016;53:591599.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Manchanda R, Menon U. Setting the threshold for surgical prevention in women at increased risk of ovarian cancer. Int J Gynecol Cancer 2018;28:3442.

  • 26.

    Manchanda R, Gaba F, Talaulikar V, et al. Risk-reducing salpingo-oophorectomy and the use of hormone replacement therapy below the age of natural menopause: scientific impact paper no. 66 October 2021: scientific impact paper no. 66. BJOG 2022;129:e1634.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Hanson H, Kulkarni A, Loong L, et al. UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes: RAD51C, RAD51D, BRIP1 and PALB2. J Med Genet 2023;60:417429.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Domchek SM, Robson ME. Update on genetic testing in gynecologic cancer. J Clin Oncol 2019;37:25012509.

  • 29.

    Eccleston A, Bentley A, Dyer M, et al. A cost-effectiveness evaluation of germline BRCA1 and BRCA2 testing in UK women with ovarian cancer. Value Health 2017;20:567576.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Morgan RD, Burghel GJ, Flaum N, et al. Prevalence of germline pathogenic BRCA1/2 variants in sequential epithelial ovarian cancer cases. J Med Genet 2019;56:301307.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Rust K, Spiliopoulou P, Tang CY, et al. Routine germline BRCA1 and BRCA2 testing in patients with ovarian carcinoma: analysis of the Scottish real-life experience. BJOG 2018;125:14511458.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Cancer Research UK. Ovarian cancer incidence statistics. Accessed July 5, 2020. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer/incidence#heading-One

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Centers for Disease Control and Prevention. Rate of new cancers by age group: all races, female. Accessed November 19, 2018. Available at: https://gis.cdc.gov/Cancer/USCS/DataViz.html

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Mersch J, Brown N, Pirzadeh-Miller S, et al. Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA 2018;320:12661274.

  • 35.

    Finch A, Beiner M, Lubinski J, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA 2006;296:185192.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 2009;101:8087.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE study group. J Clin Oncol 2004;22:10551062.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Cuzick J, Sestak I, Bonanni B, et al. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet 2013;381:18271834.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Vencken PM, Kriege M, Hoogwerf D, et al. Chemosensitivity and outcome of BRCA1- and BRCA2-associated ovarian cancer patients after first-line chemotherapy compared with sporadic ovarian cancer patients. Ann Oncol 2011;22:13461352.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    McLaughlin JR, Rosen B, Moody J, et al. Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2. J Natl Cancer Inst 2013;105:141148.

  • 41.

    Chai X, Domchek S, Kauff N, et al. RE: breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst 2015;107:djv217.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304:967975.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Mavaddat N, Antoniou AC, Mooij TM, et al. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 2020;22:8.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJ, et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst 2015;107:djv033.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Marcinkute R, Woodward ER, Gandhi A, et al. Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers. J Med Genet 2022;59:133140.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Parker WH, Feskanich D, Broder MS, et al. Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses’ health study. Obstet Gynecol 2013;121:709716.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Rivera CM, Grossardt BR, Rhodes DJ, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 2009;16:1523.

  • 48.

    Cancer Research UK. Breast cancer incidence (invasive) statistics. Accessed March 14, 2018. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/incidence-invasive#collapseOne

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    UK Office for National Statistics. Cohort fertility: England and Wales. Accessed March 20, 2018. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/conceptionandfertilityrates/datasets/cohortfertilityenglandandwales

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    National Center for Health Statistics. Cohort fertility tables. Accessed November 20, 2018. Available at: https://www.cdc.gov/nchs/nvss/cohort_fertility_tables.htm

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Manchanda R, Burnell M, Loggenberg K, et al. Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations. J Med Genet 2016;53:472480.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Schwartz MD, Valdimarsdottir HB, Peshkin BN, et al. Randomized noninferiority trial of telephone versus in-person genetic counseling for hereditary breast and ovarian cancer. J Clin Oncol 2014;32:618626.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Curtis L, Burns A, eds. Unit costs of health and social care 2016. Accessed January 8, 2018. Available at: https://www.pssru.ac.uk/project-pages/unit-costs/unit-costs-2016/

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    NHS Improvement. Archived reference costs. 2016/17 reference costs. Accessed January 8, 2018. Available at: https://webarchive.nationalarchives.gov.uk/ukgwa/20200501111106/https://improvement.nhs.uk/resources/reference-costs/

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Curtis L. Unit costs of health and social care 2011. Accessed January 8, 2018. Available at: https://www.pssru.ac.uk/project-pages/unit-costs/unit-costs-2011/

  • 56.

    Guy H, Walder L, Fisher M. Cost-effectiveness of niraparib versus routine surveillance, olaparib and rucaparib for the maintenance treatment of patients with ovarian cancer in the United States. Pharmacoeconomics 2019;37:391405.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    National Institute for Health and Care Excellence. NICE health technology evaluations: the manual. Accessed November 15, 2023. Available at: https://www.nice.org.uk/process/pmg36/chapter/introduction-to-health-technology-evaluation

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58.

    Evans DG, Lalloo F, Ashcroft L, et al. Uptake of risk-reducing surgery in unaffected women at high risk of breast and ovarian cancer is risk, age, and time dependent. Cancer Epidemiol Biomarkers Prev 2009;18:23182324.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59.

    Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018;391:10231075.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60.

    Bordeleau L, Panchal S, Goodwin P. Prognosis of BRCA-associated breast cancer: a summary of evidence. Breast Cancer Res Treat 2010;119:1324.

  • 61.

    Rennert G, Bisland-Naggan S, Barnett-Griness O, et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 2007;357:115123.

  • 62.

    Hammerschmidt T, Goertz A, Wagenpfeil S, et al. Validation of health economic models: the example of EVITA. Value Health 2003;6:551559.

  • 63.

    National Institute for Health and Care Excellence. Guide to the methods of technology appraisal 2013. Accessed March 31, 2019. Available at: https://www.nice.org.uk/process/pmg9/resources/guide-to-the-methods-of-technology-appraisal-2013-pdf-2007975843781

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64.

    Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med 2014;371:796797.

  • 65.

    Morgan RD, Burghel GJ, Flaum N, et al. BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing? Br J Cancer 2022;127:163167.

  • 66.

    Briggs A. Probabilistic analysis of cost-effectiveness models: statistical representation of parameter uncertainty. Value Health 2005;8:12.

  • 67.

    Yang X, Leslie G, Doroszuk A, et al. Cancer risks associated with germline PALB2 pathogenic variants: an international study of 524 families. J Clin Oncol 2020;38:674685.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68.

    Pal T, Akbari MR, Sun P, et al. Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer. Br J Cancer 2012;107:17831790.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 69.

    Song H, Cicek MS, Dicks E, et al. The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. Hum Mol Genet 2014;23:47034709.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70.

    Minion LE, Dolinsky JS, Chase DM, et al. Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2. Gynecol Oncol 2015;137:8692.

  • 71.

    Kwon JS, Tinker AV, Hanley GE, et al. BRCA mutation testing for first-degree relatives of women with high-grade serous ovarian cancer. Gynecol Oncol 2019;152:459464.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 72.

    Gao W, Muston D, Monberg M, et al. A critical appraisal and recommendations for cost-effectiveness studies of poly(ADP-ribose) polymerase inhibitors in advanced ovarian cancer. Pharmacoeconomics 2020;38:12011218.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 73.

    Dottino JA, Moss HA, Lu KH, et al. U.S. Food and Drug Administration-approved poly (ADP-ribose) polymerase inhibitor maintenance therapy for recurrent ovarian cancer: a cost-effectiveness analysis. Obstet Gynecol 2019;133:795802.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 74.

    Zhong L, Tran AT, Tomasino T, et al. Cost-effectiveness of niraparib and olaparib as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer. J Manag Care Spec Pharm 2018;24:12191228.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 75.

    Sundar S, Manchanda R, Gourley C, et al. British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for germline and tumour testing for BRCA1/2 variants in ovarian cancer in the United Kingdom. Accessed September 13, 2020. Available at: https://www.bgcs.org.uk/wp-content/uploads/2020/09/BGCS-BAGP-070920-final-v1.pdf

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 76.

    Penn CA, Wong MS, Walsh CS. Cost-effectiveness of maintenance therapy based on molecular classification following treatment of primary epithelial ovarian cancer in the United States. JAMA Netw Open 2020;3:e2028620.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 77.

    Boussios S, Rassy E, Moschetta M, et al. BRCA mutations in ovarian and prostate cancer: bench to bedside. Cancers (Basel) 2022;14:3888.

  • 78.

    American Society of Clinical Oncology. American Society of Clinical Oncology position statement on addressing the affordability of cancer drugs. J Oncol Pract 2018;14:187192.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 79.

    WHO. Pricing of cancer medicines and its impact. Accessed November 15, 2023. Available at: https://iris.who.int/bitstream/handle/10665/277190/9789241515115-eng.pdf?ua=1

    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 2099 2099 711
PDF Downloads 1395 1395 494
EPUB Downloads 0 0 0