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


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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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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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).

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