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

Naela Agha,Bader Alshamsan,Amgad Shahin Mohamed,Ayman Omar,Hany Salem,Fahad A Almugbel,Tusneem Elhassan,Hazem Abdullah Alotaibi,Heba Aly Ateya,Hanan Alharthy,Hamed Alhusaini,Sharifa Al-Farsi

doi:10.1186/s12885-021-09123-6

Abstract

PurposeBRCA 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.MethodsThis 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).ResultSixty-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.ConclusionThe 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 registrationTrial 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.

Highlights

In high-income countries, ovarian cancer (OC) is the second most commonly diagnosed gynecological malignancy and the most common cause of death from it [1]
Poly ADP-ribose polymerase enzyme (PARP) inhibitors induce the synthetic lethality of cells with homologous recombination defect (HRD), which occurs when there is a simultaneous mutation in two genes leading to cell death; no cell death occurs when the mutation is found in only one gene [12]
A retrospective study was conducted on all patients diagnosed with primary ovarian, fallopian tube, or peritoneal carcinoma who were tested for BRCAmutations and followed up at the King Abdullah Oncology Centre at the King Faisal Specialist Hospital and Research Center (KFSH&RC) between January 2016 and December 2017

Summary

Introduction

In high-income countries, ovarian cancer (OC) is the second most commonly diagnosed gynecological malignancy and the most common cause of death from it [1]. Evidence showed improvement in objective response rate (ORR) and progression-free survival (PFS) in heavily treated patients, predominantly in those with either germline or somatic BRCAmutations as HRD occurs in germline BRCAmutations, somatic BRCAmutations, and BRCApromotor hypermethylation cases [14]. This benefit has recently been proven to involve women with advanced high-grade serous OC after response to platinum-based chemotherapy (PBC) regardless of BRCA status [15]. The standard therapy for advanced epithelial OC is PBC following primary debulking surgery (PDS)

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