Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women

Abstract

Purpose BRCA gene mutations (BRCAm) have an impact on patients’ characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. Methods This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). Result Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. Conclusion The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. Trial registration Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Constitutional BRCA1 and MGMT Methylation Are Significant Risk Factors for Triple-Negative Breast Cancer and High-Grade Serous Ovarian Cancer in Saudi Women

“…MGMT methylation, on the other hand, was found to be strongly linked to BC and, in particular, to late-onset BC, and this finding is in concordance with our previous study [ 4 ]. Given the higher frequency of TNBC among younger females [ 29 , 30 , 31 ], it is not surprising that our findings demonstrate a strong correlation between TNBC and constitutional BRCA1 methylation rather than constitutional MGMT methylation. Nevertheless, these data reveal that BRCA1 and MGMT epimutations account for about 28% of overall BC and 39% of the TNBC subtype among Saudi female BC patients.…”

“…Notably, our findings show that BRCA1 and MGMT epimutations account for almost 30% of all OC and almost 43% of severe HGSOC in Saudi patients. Given that the prevalence of pathogenic BRCA1 mutations varies between 24% and 41% [ 26 , 30 ], this suggests that potentially up to 70% of ovarian cancer cases might be anticipated and avoided at an early stage.…”

Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel

“…The BRCA1 variant c5530delC, which has been flagged as unique among Saudi Arabian ovarian cancer patients [ 45 ], and one of the most common variants observed in another Saudi Arabian ovarian cancer cohort by Agha et al [ 49 ], was present in one subject with ovarian cancer, with each patient carrying a different variant (3 in BRCA1 , 1 in APC , 1 in TP53 , see Supplementary Table 3). We note a similar overall incidence of BRCA1 mutation in association with ovarian cancer between this study and that of Agha et al (60% vs. 77%), although our ovarian cancer patient pool is small.…”

The Histopathological Patterns of Ovarian Neoplasms in Different Age Groups: A Retrospective Study in a Tertiary Care Center

“…Some studies, such as the one done by George and Shaw have found an association between serous ovarian cancer and BRCA gene mutation [ 22 ]. According to a recent study done by Agha et al, BRCA mutation was found in 41% of Saudi women diagnosed with ovarian cancer [ 23 ]. While assessing the frequency of BRCA mutation was not within the scope of this study, we hypothesize that the increase in the prevalence of ovarian malignancy in Saudi for the past 10 years could possibly be attributed to the high prevalence of BRCA mutation.…”