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Mainstreaming germline BRCA1/2 testing in non-mucinous epithelial ovarian cancer in the North West of England

European Journal of Human Genetics volume 28, pages 1541–1547 (2020)Cite this article

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Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors improve survival in BRCA-mutant high-grade serous ovarian carcinoma. As a result, germline and somatic BRCA1/2 testing has become standard practice in women diagnosed with ovarian cancer. We outline changes in testing and detection rates of germline BRCA1/2 pathogenic variants (PVs) in cases of non-mucinous epithelial ovarian cancer diagnosed during three eras, spanning 12 years, within the North West of England, and compare the uptake of cascade testing in families identified by oncology-led mainstreaming versus regional genetics clinics. Eras included: Period 1 (20% risk threshold for testing): between January 2007 and May 2013; Period 2 (10% risk threshold for testing): between June 2013 and October 2017 and; Period 3 (mainstream testing): between November 2017 and November 2019. A total of 1081 women underwent germline BRCA1/2 testing between January 2007 and November 2019 and 222 (20.5%) were found to have a PV. The monthly testing rate increased by 3.3-fold and 2.5-fold between Periods 1–2 and Periods 2–3, respectively. A similar incidence of germline BRCA1/2 PVs were detected in Period 2 (17.2%) and Period 3 (18.5%). Uptake of cascade testing from first-degree relatives was significantly lower in those women undergoing mainstream testing compared with those tested in regional genetics clinics (31.6% versus 47.3%, P = 0.038). Mainstream testing allows timely detection of germline BRCA1/2 status to select patients for PARP inhibitors, but shortfalls in the uptake of cascade testing in first-degree relatives requires optimisation to broaden benefits within families.

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Fig. 1: Kaplan–Meier curve.

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Acknowledgements

ERW, EJC, EFH, and DGRE are supported by the all Manchester National Institute for Health Research Manchester Biomedical Research Centre (IS-BRC-1215-20007).

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Author notes

  1. These authors contributed equally: Nicola Flaum, Robert D. Morgan

Authors and Affiliations

  1. The Christie NHS Foundation Trust, Manchester, UK

    Nicola Flaum, Robert D. Morgan, Andrew R. Clamp, Jurjees Hasan, Claire L. Mitchell & Gordon C. Jayson

  2. Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    Nicola Flaum, Robert D. Morgan, Emma J. Crosbie, Richard J. Edmondson & Gordon C. Jayson

  3. St Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester, UK

    George J. Burghel, Michael Bulman, Tara Clancy, Helene Schlecht, Emma R. Woodward, Emma J. Crosbie, Richard J. Edmondson, Andrew J. Wallace, Fiona I. Lalloo & D. Gareth R. Evans

  4. Royal Blackburn Teaching Hospital, East Lancashire Hospitals NHS Trust, Blackburn, UK

    Doina Badea

  5. Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK

    Sarah Moon, Martin Hogg & Dennis Hadjiyiannakis

  6. Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    Elaine F. Harkness

  7. Genesis Breast Cancer Prevention Centre, Manchester University NHS Foundation Trust, Manchester, UK

    Elaine F. Harkness

  8. Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    D. Gareth R. Evans

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Corresponding author

Correspondence to D. Gareth R. Evans.

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The authors declare that they have no conflict of interest.

Ethical approval

The germline BRCA1/2 database is approved by North Manchester Research Ethics Committee (08/H1006/77). All women included in this study provided informed verbal and/or written consent to undergo germline BRCA1/2 testing.

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Flaum, N., Morgan, R.D., Burghel, G.J. et al. Mainstreaming germline BRCA1/2 testing in non-mucinous epithelial ovarian cancer in the North West of England. Eur J Hum Genet 28, 1541–1547 (2020). https://doi.org/10.1038/s41431-020-0692-y

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