Introduction/Background Pathogenic germline BRCA1 and BRCA2 (BRCA) variants are frequent in high-grade serous ovarian cancer (HGSOC). Age, tumor stage, and residual disease are known predictors of survival. However, it is not clear whether these associations differ by BRCA variant status. We examined the association between clinicopathological features and survival by BRCA status, in a large cohort of HGSOC patients.
Methodology We evaluated clinicopathological and germline DNA sequencing data on 1,405 patients with HGSOC from 17 Australian treatment centres, enrolled into the Australian Ovarian Cancer Study between 2002–2023. Multivariate Cox proportional hazards models and logistic regression analysis were used to assess the association between prognostic factors and outcomes by BRCA status.
Results The study population consisted of 1,112 (79.1%) non-carriers and 293 (20.9%) BRCA mutation carriers. Age, FIGO stage, BRCA status, primary site and residual disease showed a significant association with survival after risk factor adjustment. Non-carriers with residual disease showed a poorer overall survival compared to non-carriers with no residual disease (p<0.001, HR: 2.10, 95%CI: 1.75–2.50), whereas there was no significant difference in survival for patients with BRCA germline alterations with or without residual disease (p=0.188 and 0.221, HR: 1.17 and 0.8, 95%CI: 0.91–1.50 and 0.57–1.10, respectively). Patients with primary peritoneal carcinoma had a poorer survival than those with primary ovarian HGSOC (p=0.002, HR:1.33, 95%CI: 1.11–1.60). Patients with protein-truncating BRCA mutations had a better survival than those with splice-site, missense or structural variants (p<0.001). The results of the logistic regression analysis model aligned with the multivariate cox regression model.
Conclusion Our results suggest that the adverse effect of residual disease is stronger for non-carriers compared to patients with a germline BRCA mutation. Thus, while optimal debulking improves outcomes for all patients with HGSOC, it may be particularly important to achieve no residual disease for non-carriers.
Disclosures David D.L. Bowtell reports research support grants from AstraZeneca, Roche-Genentech and BeiGene outside the submitted work; also personal consulting fees from Exo Therapeutics, that are outside the submitted work. Anna DeFazio reports support grants and personal consulting fees from AstraZeneca outside the submitted work. All other authors declare that they have no conflicts of interest.
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