Kalachand, Roshni D. and Stordal, Britta and Madden, Stephen and Chandler, Benjamin and Cunningham, Julie and Goode, Ellen L. and Ruscito, Ilary and Braicu, Elena and Sehouli, Jalid and Ignatov, Atanas and Yu, Herbert and Katsaros, Dionyssios and Mills, Gordon B. and Lu, Karen H. and Carey, Mark S. and Timms, Kirsten M. and Kupryjanczyk, Jolanta and Rzepecka, Iwona K. and Podgorska, Agnieszka and McAlpine, Jessica N. and Swisher, Elizabeth M. and Bernards, Sarah S. and O'Riain, Ciaran and O'Toole, Sharon and O'Leary, John J. and Bowtell, David D. and Thomas, David M. and Prieske, Katharina and Joosse, Simon A. and Woelber, Linn and Chaudhry, Parvesh and Hafner, Norman and Runnebaum, Ingo B. and Hennessy, Bryan T. (2020) BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 112 (12). pp. 1190-1203. ISSN 0027-8874, 1460-2105
Full text not available from this repository. (Request a copy)Abstract
Background: BRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal and ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of individual participant data. Methods: Data of 2636 participants across 15 studies were analyzed. BRCA1-methylated tumors were defined according to their original study. Associations between BRCA1 methylation and clinicopathological characteristics were evaluated. The effects of methylation on overall survival (OS) and progression-free survival (PFS) were examined using mixed-effects models. All statistical tests were 2-sided. Results: 430 (16.3%) tumors were BRCA1-methylated. BRCA1 methylation was associated with younger age and advanced-stage, high-grade serous OC. There were no survival differences between BRCA1-methylated and non-BRCA1-methylated OC (median PFS = 20.0 vs 18.5 months, hazard ratio [HR] = 1.01, 95% CI = 0.87 to 1.16; P = .98; median OS = 46.6 vs 48.0 months, HR = 1.02, 95% CI = 0.87 to 1.18; P = .96). Where BRCA1/2 mutations were evaluated (n = 1248), BRCA1 methylation displayed no survival advantage over BRCA1/2-intact (BRCA1/2 wildtype non-BRCA1-methylated) OC. Studies used different methods to define BRCA1 methylation. Where BRCA1 methylation was determined using methylation-specific polymerase chain reaction and gel electrophoresis (n = 834), it was associated with improved survival (PFS: HR = 0.80, 95% CI = 0.66 to 0.97; P = .02; OS: HR = 0.80, 95% CI = 0.63 to 1.00; P = .05) on mixedeffects modeling. Conclusion: BRCA1-methylated OC displays similar clinicopathological features to BRCA1-mutated OC but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLATINUM-BASED CHEMOTHERAPY; ALLELIC LOSS; SURVIVAL; MUTATIONS; HYPERMETHYLATION; EXPRESSION; CARCINOMA; BREAST; REGION; IMMUNOHISTOCHEMISTRY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) |
| Depositing User: | Petra Gürster |
| Date Deposited: | 21 Apr 2021 12:42 |
| Last Modified: | 21 Apr 2021 12:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43190 |
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