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

Article

Kalachand, R., O'Riain, C., Toomey, S., Carr, A., Timms, K., O'Toole, S., Madden, S., Bates, M., O'Leary, J., Gleeson, N., O'Donnell, D., Grogan, L., Breathnach, O., Farrelly, A., Stordal, B. and Hennessy, B. 2020. Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer. Obstetrics & Gynecology Science. 63 (5), pp. 643-654. https://doi.org/10.5468/ogs.20033
TypeArticle
TitlePrevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer
AuthorsKalachand, R., O'Riain, C., Toomey, S., Carr, A., Timms, K., O'Toole, S., Madden, S., Bates, M., O'Leary, J., Gleeson, N., O'Donnell, D., Grogan, L., Breathnach, O., Farrelly, A., Stordal, B. and Hennessy, B.
Abstract

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.

KeywordsOvarian cancer; BRCA1 methylation; BRCA1 mutation; BRCA2 mutation
Sustainable Development Goals3 Good health and well-being
Research GroupBiomarkers for Cancer group
PublisherKorean Society of Obstetrics and Gynecology
JournalObstetrics & Gynecology Science
ISSN2287-8572
Electronic2287-8580
Publication dates
Online02 Sep 2020
Print15 Sep 2020
Publication process dates
Deposited06 Jul 2022
Accepted06 May 2020
Output statusPublished
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Copyright Statement

Copyright © 2020 Korean Society of Obstetrics and Gynecology
Articles published in Obstet Gynecol Sci are open-access, distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Digital Object Identifier (DOI)https://doi.org/10.5468/ogs.20033
PubMed ID32872764
PubMed Central ID7494761
Web of Science identifierWOS:000905558600011
LanguageEnglish
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