Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study
File(s)Morgan_IntJGynecolCancer_2023.pdf (1.55 MB)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2023-04-24
Date Acceptance
2023-04-07
Citation
International Journal of Gynecological Cancer, 2023, 33 (8), pp.1253-1259
ISSN
1048-891X
Publisher
BMJ Publishing Group
Start Page
1253
End Page
1259
Journal / Book Title
International Journal of Gynecological Cancer
Volume
33
Issue
8
Copyright Statement
Copyright © 2023 The Author(s). This article has been accepted for publication in International Journal of Gynecologic Cancer, 2023 following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/10.1136/ijgc-2022-004211
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37072323
PII: ijgc-2022-004211
Subjects
BRCA1 Protein
BRCA2 Protein
Homologous recombination
Ovarian Cancer
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2023-04-18