You are here

  • Home
  • Online First
  • Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study

Article Text

Article menu

other Versions

Download PDFPDF
Original research
Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study
  1. Robert D Morgan1,2,
  2. Andrew R Clamp1,2,
  3. Bethany M Barnes2,
  4. Kirsten Timms3,
  5. Helene Schlecht4,
  6. Laura Yarram-Smith5,
  7. Yvonne Wallis6,
  8. Mikel Valganon-Petrizan7,
  9. Suzanne MacMahon7,
  10. Rhian White8,
  11. Sian Morgan8,
  12. Sarah McKenna9,
  13. Emma Hudson10,
  14. Laura Tookman11,
  15. Angela George12,13,
  16. Ranjit Manchanda14,15,16,
  17. Sudha S Sundar17,18,
  18. Shibani Nicum19,20,
  19. James D Brenton21,22,
  20. Rebecca S Kristeleit23,
  21. Susana Banerjee12,13,
  22. Iain A McNeish11,24,
  23. Jonathan A Ledermann19,20,
  24. Stephen S Taylor2,
  25. D Gareth R Evans25,26 and
  26. Gordon C Jayson1,2
  1. 1The Christie NHS Foundation Trust, Manchester, UK
  2. 2Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
  3. 3Myriad Genetics, Inc, Salt Lake City, Utah, USA
  4. 4North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK
  5. 5South West Genomic Laboratory Hub, North Bristol NHS Trust, Bristol, UK
  6. 6Central and South Genomic Laboratory Hub, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UK
  7. 7North Thames Genomic Laboratory Hub, The Royal Marsden Hospital NHS Foundation Trust, Surrey, UK
  8. 8All Wales Genomics Laboratory, Institute of Medical Genetics, University Hospital Wales, Cardiff, UK
  9. 9Belfast Health and Social Care Trust, Belfast, UK
  10. 10Velindre University NHS Trust, Cardiff, UK
  11. 11Imperial College Healthcare NHS Trust, London, UK
  12. 12The Royal Marsden NHS Foundation Trust, London, UK
  13. 13The Institute of Cancer Research, London, UK
  14. 14Barts Health NHS Trust, London, UK
  15. 15Department of Health Services Research, The Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK
  16. 16Wolfson Institute of Population Health, Queen Mary's University of London, London, UK
  17. 17Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
  18. 18Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
  19. 19University College London Hospitals NHS Foundation Trust, London, UK
  20. 20UCL Cancer Institute, London, UK
  21. 21Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  22. 22CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
  23. 23Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  24. 24Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK
  25. 25Manchester University NHS Foundation Trust, Manchester, UK
  26. 26Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
  1. Correspondence to Dr Robert D Morgan, The Christie NHS Foundation Trust, Manchester, UK; robert.morgan7{at}nhs.net

Abstract

Objective Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022.

Methods The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumors with homologous recombination deficiency were those with a BRCA1/2 mutation and/or a Genomic Instability Score (GIS) ≥42. Testing was coordinated by the NHS Genomic Laboratory Hub network.

Results The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent BRCA1/2 and GIS testing, respectively. All complete and partial assay failures occurred due to low tumor cellularity and/or low tumor DNA yield. 385 tumors (16%) contained a BRCA1/2 mutation and 814 (37%) had a GIS ≥42. Tumors with a GIS ≥42 were more likely to be BRCA1/2 wild-type (n=510) than BRCA1/2 mutant (n=304). The distribution of GIS was bimodal, with BRCA1/2 mutant tumors having a higher mean score than BRCA1/2 wild-type tumors (61 vs 33, respectively, χ2 test p<0.0001).

Conclusion This is the largest real-world evaluation of homologous recombination deficiency testing in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is important to select tumor tissue with adequate tumor content and quality to reduce the risk of assay failure. The rapid uptake of testing across England, Wales, and Northern Ireland demonstrates the power of centralized NHS funding, center specialization, and the NHS Genomic Laboratory Hub network.

  • BRCA1 Protein
  • BRCA2 Protein
  • Homologous recombination
  • Ovarian Cancer

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/ijgc-2022-004211

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.

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

    View Full Text

    Footnotes

    • Twitter @sundar_sudha

    • Contributors RDM, ARC, BMB, KT, SST, DGRE and GCJ wrote the original version of the manuscript. All authors reviewed and agreed to the final version of the manuscript. RDM is the guarantor.

    • Funding The Myriad myChoice® companion diagnostic was funded by AstraZeneca PLC (Address: 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK; Tel: +44 (0)20 3749 5000).

    • Competing interests RDM, BMB, HS, LY-S, YW, MV-P, RW, SM, SMc, EH, AG, SS, SN, SST and DGRE declare no conflicts of interest. KT is an employee and stockholder of Myriad Genetics, Inc. ARC declares research funding from AstraZeneca. SMac declares travel funding and speaker fees from AstraZeneca, Merck and Eli Lily. LT declares honoraria from AstraZeneca, Clovis Oncology, GSK and Tesaro. RM declares honoraria from AstraZeneca, Merck Sharp & Dohme and GSK and research funding from Barts & The London Charity, Rosetrees Trust, GSK and Yorkshire Cancer Research. JDB declares honoraria from AstraZeneca and GSK and consulting and advisory roles in Clovis Oncology and GSK. SB declares institutional grants from AstraZeneca and GSK, personal fees for speaker, consulting/advisory roles from Amgen, AstraZeneca, Clovis Oncology, Epsilogen, GSK, Immunogen, Mersana, Merck Sharp & Dohme, Merck Serono, Novartis, OncXerna, Pfizer, Roche, Shattuck Labs & Takeda. RSK declares honoraria from AstraZeneca, Clovis Oncology, GSK and Incyte and travel support from AstraZeneca, GSK and Sierra Oncology and trial grants from Merck Sharp & Dohme and consulting fees from Basilea Pharmaceutica and Shattuck Pharma. IMcN declares honoraria from AstraZeneca, Clovis Oncology, Epsila Bio, GSK, Roche and Scancell and institutional funding from AstraZeneca. JAL declares honoraria from AstraZeneca, Clovis Oncology, GSK, Eisai, Neopharm, Artios Pharma, Merck/Merck Sharp & Dohme, Mersana, Regeneron, VBL Therapeutics, Nuvation and Bristol Myers Squibb. GCJ declares research funding from AstraZeneca.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.