Dataset Information

BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis.

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 wild-type 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 mixed-effects 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.

SUBMITTER: Kalachand RD

PROVIDER: S-EPMC7735770 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis.

Kalachand Roshni D RD Stordal Britta B Madden Stephen S Chandler Benjamin B Cunningham Julie J Goode Ellen L EL Ruscito Ilary I Braicu Elena I EI Sehouli Jalid J Ignatov Atanas A Yu Herbert H Katsaros Dionyssios D Mills Gordon B GB Lu Karen H KH Carey Mark S MS Timms Kirsten M KM Kupryjanczyk Jolanta J Rzepecka Iwona K IK Podgorska Agnieszka A McAlpine Jessica N JN Swisher Elizabeth M EM Bernards Sarah S SS O'Riain Ciaran C O'Toole Sharon S O'Leary John J JJ Bowtell David D DD Thomas David M DM Prieske Katharina K Joosse Simon A SA Woelber Linn L Chaudhry Parvesh P Häfner Norman N Runnebaum Ingo B IB Hennessy Bryan T BT

Journal of the National Cancer Institute 20201201 12

<h4>Background</h4>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.<h4>Methods</h4>Data of 2636 participants across 15 studies were analyzed. BRCA1-methylated tumors were defined acc ...[more]

PMID: 32413141

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Dataset Information

BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis.

Background

Methods

Results

Conclusion

Publications

BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis.

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