Document Type
Article
Publication Date
5-30-2024
Abstract
OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group.
METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed).
RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36).
CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Pitiyarachchi, Omali; Ansell, Peter J.; Coleman, Robert L.; Dinh, Minh H.; Holman, Laura; Leath, Charles A.; Werner, Theresa; DiSilvestro, Paul; Morgan, Mark; Tew, William; Lee, Christine; Cunningham, Mary; Newton, Meredith; Edraki, Babak; Lim, Peter; Barlin, Joyce; Spirtos, Nicola M.; Tewari, Krishnansu S.; Edelson, Mitchell I.; Reid, Thomas; Carlson, Jay; and Friedlander, Michael, "Homologous Recombination Deficiency Should Be Tested for in Patients With Advanced Stage High-Grade Serous Ovarian Cancer Aged 70 Years and Over" (2024). Abington Jefferson Health Papers. Paper 99.
https://jdc.jefferson.edu/abingtonfp/99
PubMed ID
38821039
Language
English
Comments
This article is the author's final published version in Gynecologic Oncology, Volume 187, 2024, Pages 221 - 226.
The published version is available at https://doi.org/10.1016/j.ygyno.2024.05.021.
Copyright © 2024 The Authors