Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study.
Date
2023-08-07ICR Author
Author
Morgan, RD
Clamp, AR
Barnes, BM
Timms, K
Schlecht, H
Yarram-Smith, L
Wallis, Y
Valganon-Petrizan, M
MacMahon, S
White, R
Morgan, S
McKenna, S
Hudson, E
Tookman, L
George, A
Manchanda, R
Sundar, SS
Nicum, S
Brenton, JD
Kristeleit, RS
Banerjee, S
McNeish, IA
Ledermann, JA
Taylor, SS
Evans, DGR
Jayson, GC
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
BRCA1 Protein
BRCA2 Protein
Homologous recombination
Ovarian Cancer
Female
Humans
Carcinoma, Ovarian Epithelial
BRCA1 Protein
Ovarian Neoplasms
State Medicine
BRCA2 Protein
Genomic Instability
Homologous Recombination
Mutation
Language
eng
Date accepted
2023-04-07
License start date
2023-08-07
Citation
International Journal of Gynecological Cancer, 2023, 33 (8), pp. 1253 - 1259
Publisher
BMJ PUBLISHING GROUP