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Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer

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posted on 2023-01-11, 16:31 authored by Roshni Kalachand, Ciaran O'Riain, Sinead ToomeySinead Toomey, Aoife Carr, Kirsten M Timms, Sharon O'Toole, Stephen MaddenStephen Madden, Mark Bates, John J O'Leary, Noreen Gleeson, Dearbhaile O'Donnell, Liam GroganLiam Grogan, Oscar BreathnachOscar Breathnach, Angela Farrelly, Britta Stordal, Bryan HennessyBryan Hennessy

Objective: The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC.

Methods: We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher's exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]).

Results: We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43-0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22-1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51-1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers.

Conclusion: We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.


St. Luke’s Institute of Cancer Research

Northeast Cancer Research & Education Trust



The original article is available at https://ogscience.org/

Published Citation

Kalachand RD. et al. Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer. Obstet Gynecol Sci. 2020;63(5):643-654

Publication Date

2 September 2020

PubMed ID



  • Beaumont Hospital
  • Data Science Centre
  • Molecular Medicine

Research Area

  • Cancer
  • Neurological and Psychiatric Disorders
  • Gynaecology, Obstetrics and Perinatal Health


Korean Society of Obstetrics and Gynecology


  • Published Version (Version of Record)