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Cancer genetics
Original research
Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers
  1. Ruta Marcinkute1,
  2. Emma Roisin Woodward2,3,
  3. Ashu Gandhi4,
  4. Sacha Howell4,5,
  5. Emma J Crosbie6,7,
  6. Julie Wissely4,
  7. James Harvey4,
  8. Lindsay Highton4,
  9. John Murphy4,
  10. Cathrine Holland7,
  11. Richard Edmondson6,7,
  12. Richard Clayton7,
  13. Lester Barr4,
  14. Elaine F Harkness4,8,
  15. Anthony Howell4,5,
  16. Fiona Lalloo9,
  17. D Gareth Evans2,3,4,10
  1. 1Clinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  2. 2Manchester Centre for Genomic Medicine, Central Manchester NHS Foundation Trust, Manchester, UK
  3. 3Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  4. 4Prevent Breast Cancer Centre, Wythenshawe Hospital Manchester Universities Foundation Trust, Manchester, UK
  5. 5Manchester Breast Centre, The Christie Hospital, Manchester, UK
  6. 6Division of Cancer Sciences, Faculty of Biology, Medicine and Health, St Mary’s Hospital, University of Manchester, Manchester, UK
  7. 7Department of Obstetrics and Gynaecology, St Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  8. 8Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  9. 9Clinical Genetics Service, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  10. 10NW Genomic Laboratory Hub, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  1. Correspondence to Professor D Gareth Evans, Clinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK; gareth.evans{at}mft.nhs.uk

Abstract

Background Women testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy BRCA1/2 carriers.

Methods Women were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk.

Results In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range=0.01–24.3; total=4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9% and RRSO uptake was 78.6%. The median time from GT to RRM was 18.4 months, and from GT to RRSO–10.0 months. Annual BC incidence in the study population was 1.28%. Relative BC risk reduction (RRM versus non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100%.

Conclusion Over a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.

  • Genetic Predisposition to Disease
  • Genetics

https://doi.org/10.1136/jmedgenet-2020-107356

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    Footnotes

    • Twitter @ER_Woodward, @DrEmmaCrosbie

    • Contributors The research, literature review and manuscript text was conducted by RM, with a supervision and significant input from DGE. The other authors contributed with clinical work, patients inclusion, manuscript review and revision review.

    • Funding EJC is a National Institute for Health Research (NIHR) Clinician Scientist (NIHR-CS-012–009) and DGE is an NIHR Senior Investigator (NF-SI-0513–10076). DGE, EJC, EFH and ERW are supported by the all Manchester NIHR Biomedical Research Centre (IS-BRC-1215–20007).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval North Manchester Research Ethics Committee (reference 08/H1006/77).

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

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

    • 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.