1. Mainstreaming germline BRCA1/2 testing in non-mucinous epithelial ovarian cancer in the North West of England
- Author
-
Andrew R Clamp, Gordon C Jayson, Martin Hogg, Sarah Moon, Doina Badea, Helene Schlecht, Fiona Lalloo, Elaine F. Harkness, Jurjees Hasan, Nicola Flaum, Dennis Hadjiyiannakis, Tara Clancy, Andrew J Wallace, George J Burghel, Claire Mitchell, Richard J. Edmondson, Robert D. Morgan, Emma J Crosbie, M Bulman, Emma R. Woodward, and D. Gareth Evans
- Subjects
Adult ,medicine.medical_specialty ,Carcinoma, Ovarian Epithelial ,Article ,Germline ,Ovarian carcinoma ,Internal medicine ,Genetics ,medicine ,Humans ,Epithelial ovarian cancer ,Genetic Testing ,Risk threshold ,Germ-Line Mutation ,Genetics (clinical) ,Aged ,BRCA2 Protein ,Ovarian Neoplasms ,BRCA1 Protein ,business.industry ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,Serous fluid ,England ,North west ,Female ,Ovarian cancer ,business - 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.
- Published
- 2020