scholarly journals Assessing Frequency and Clinical Outcomes of BRCA Mutated Ovarian Cancer in Saudi Women

2021 ◽  
Author(s):  
Naela Agha ◽  
Bader Alshamsan ◽  
Sharifa Al-Farsi ◽  
Heba Aly Ateya ◽  
Fahed A Almugbel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Saudi Arabia ◽  
Clinical Outcomes ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Research Center ◽  
Brca Mutations ◽  
Frequency Pattern ◽  
Saudi Women ◽  
King Faisal Specialist Hospital

Abstract Purpose: BRCA gene mutations (BRCAm) had 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 number and The addresses of the institution at which the work was performed: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 11211, Saudi Arabia.

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

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Naela Agha ◽  
Bader Alshamsan ◽  
Sharifa Al-Farsi ◽  
Heba Aly Ateya ◽  
Fahad A. Almugbel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Saudi Arabia ◽  
Clinical Outcomes ◽  
Gene Mutations ◽  
Patient Characteristics ◽  
Research Center ◽  
Frequency Pattern ◽  
Saudi Women ◽  
Platinum Sensitive ◽  
King Faisal Specialist Hospital

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.

scholarly journals Assessing Frequency and Clinical Outcomes of BRCA Mutated Ovarian Cancer in Saudi Women

2020 ◽  
Author(s):  
Naela Agha ◽  
Bader Alshamsan ◽  
Sharifa Al-Farsi ◽  
Heba Aly Ateya ◽  
Fahed A Almugbel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcomes ◽  
Brca1 Mutation ◽  
Objective Response ◽  
Disease Free Survival ◽  
Serous Carcinoma ◽  
Free Access ◽  
First Line ◽  
Brca Mutations ◽  
Saudi Women

Abstract Background: BRCA gene mutations (BRCAm) had 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.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. The objective response rate (ORR) of the first line and subsequent lines for BRCAm and BRCAw were evaluated using Response Evaluation Criteria in Solid Tumors Version 1. The disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier methods and compared by log-rank tests.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 majority were BRCA 1 (92%), and the most common deleterious germline BRCA1 mutation was c.1140dupG (39%), followed by c.5530del (13%) and c.5095C>T (8%). Most women (72%) had no family history of cancers, all had high-grade serous carcinoma, and 82% had advanced stage at presentation. Regardless of BRCA mutations, an optimal ORR to first-line treatment has been achieved although most cases relapsed after the first line of management (84%) and the majority were platinum-sensitive relapse (85%). The ORR was higher in BRCAm in subsequent lines compared to BRCAw type. BRCAm women experienced longer median DFS (25 vs 17 months, p = 0.02) and a higher five-year OS rate (90.9% vs 66.7%, p = 0.19) than BRCAw.Conclusion: The prevalence of BRCAm of OC was higher in Saudi women when compared with the regional and most of the international figures. The better clinical outcomes of BRCAm women is in concordance with the reported evidence. Further studies on BRCA mutations of OC, education, genetic counseling, and free access to genetic testing are highly recommended.

scholarly journals High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes

Radiology ◽  
2017 ◽  
Vol 285 (2) ◽  
pp. 472-481 ◽  
Author(s):  
Stephanie Nougaret ◽  
Yulia Lakhman ◽  
Mithat Gönen ◽  
Debra A. Goldman ◽  
Maura Miccò ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcomes ◽  
Brca Mutation ◽  
Ct Imaging ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Mutation Status

scholarly journals Factors influencing women’s decisions to getting tested for BRCA mutation

2018 ◽  
Vol 9 (3) ◽  
pp. 33 ◽  
Author(s):  
Suha Al-Oballi Kridli ◽  
Holly Austin
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Genetic Mutations ◽  
Inclusion Criteria ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Factors Influencing ◽  
Brca1 And Brca2 Mutations ◽  
Internal And External Factors

Ovarian cancer is the leading cause of death among gynecological cancers. There are many risk factors that can increase a woman’s susceptibility to breast and ovarian cancers, some of which are modifiable.  However, non-modifiable risks for breast and ovarian cancer include the presence of genetic mutations (BRCA) increase the risk of these diseases. The purpose of this review was to identify factors, reported in the literature, known to affect women’s decision to get genetic testing for BRCA1 and BRCA2 mutations for hereditary breast and ovarian cancer. A total of 31 studies that met the inclusion criteria were included in this review. Several internal and external factors, influencing women’s decision to getting tested for BRCA mutations, were identified and explained. Implications for clinical practice were provided.

scholarly journals Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 416 ◽  
Author(s):  
Ainhoa Madariaga ◽  
Stephanie Lheureux ◽  
Amit Oza
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Repair Process ◽  
Resistance Mechanisms ◽  
Tumour Suppressor Genes ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Damage Repair ◽  
Brca Mutation Carriers ◽  
Drug Efflux Pumps

High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.

scholarly journals Gynecologic Cancers: Emerging Novel Strategies for Targeting DNA Repair Deficiency

2016 ◽  
pp. e259-e268 ◽  
Author(s):  
Rebecca S. Kristeleit ◽  
Rowan E. Miller ◽  
Elise C. Kohn
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Inhibitor Therapy ◽  
Molecular Therapy ◽  
Parp Inhibition ◽  
Gynecologic Cancers ◽  
Brca Mutations ◽  
Individual Gene

The presence of a BRCA mutation, somatic or germline, is now established as a standard of care for selecting patients with ovarian cancer for treatment with a PARP inhibitor. During the clinical development of the PARP inhibitor class of agents, a subset of women without BRCA mutations were shown to respond to these drugs (termed “ BRCAness”). It was hypothesized that other genetic abnormalities causing a homologous recombinant deficiency (HRD) were sensitizing the BRCA wild-type cancers to PARP inhibition. The molecular basis for these other causes of HRD are being defined. They include individual gene defects (e.g., RAD51 mutation, CHEK2 mutation), homozygous somatic loss, and whole genome properties such as genomic scarring. Testing this knowledge is possible when selecting patients to receive molecular therapy targeting DNA repair, not only for patients with ovarian cancer but also endometrial and cervical cancers. The validity of HRD assays and multiple gene sequencing panels to select a broader population of patients for treatment with PARP inhibitor therapy is under evaluation. Other non-HRD targets for exploiting DNA repair defects in gynecologic cancers include mismatch repair (MMR), checkpoint signaling, and nonhomologous end-joining (NHEJ) DNA repair. This article describes recent evidence supporting strategies in addition to BRCA mutation for selecting patients for treatment with PARP inhibitor therapy. Additionally, the challenges and opportunities of exploiting DNA repair pathways other than homologous recombination for molecular therapy in gynecologic cancers is discussed.

Somatic versus germline BRCA mutations screening in ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13100-e13100
Author(s):  
Hugo SM Nunes ◽  
Patricia Machado ◽  
Sofia Fragoso ◽  
Sidonia Santos ◽  
Fernanda Silva ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Somatic Mutations ◽  
Brca Mutation ◽  
Point Mutations ◽  
Parp Inhibitors ◽  
Brca Mutations ◽  
Alu Element ◽  
Brca1 Carriers ◽  
Large Rearrangements ◽  
Clinic Medical

e13100 Background: ovarian cancer (OC) with germinal or somatic BRCA mutations responds better to platinum and to PARP-inhibitors. There is great enthusiasm about BRCA somatic screening. Our aim was to analyse the correlation between BRCA somatic and germline mutational profile. Methods: a cohort of 23 pts was obtained by cross-linking OC pts from the South Portuguese Cancer Registry, between 2009-2014 and BRCA mutation carriers identified in our Clinic. Medical records were reviewed: demographic and clinico-pathologic data obtained. Germinal screening: pts were pre-screened for the BRCA2 Portuguese founder mutation (PFM), analysed for BRCA point mutations (different screening methodologies were used in diagnostic timeline: initially CSGE, then CSCE and finally NGS) and for large rearrangements by MLPA. Somatic screening: DNA was extracted from 5 sections of 10µm of FFPE tissue and analysed for BRCA1/2 genes by NGS. Results: clinico-pathological features of the 23 pts revealed mainly high-grade serous histology (96%). Mean age at diagnosis was 54 years old (33-76); BRCA2 were older than BRCA1 carriers (62 vs 51). Most pts presented at advanced stage (70% stages III-IV; 30% stage I-II). Seventeen were BRCA1 carriers and 6 were BRCA2 (5 of those PFM, a large insertion of an Alu element). Somatic correlation: 8 pts (5 BRCA1, 3PFM) were already analysed and 100% correlation was observed for all point mutations. One additional BRCA2 somatic mutation was detected (with a variant allele frequency of 53% whereas 2 others were < 7%); interestingly exclusive somatic mutations were only observed in PFM carriers (known not to be NGS detectable). The remaining 15 pts are under analysis. Conclusions: it was expected that the PFM and other large rearrangements would not be detected with NGS. A specific somatic screening for the PFM may be possible but other rearrangements are found by MLPA in our population (10% of all BRCA mutations). Preliminary data adds to the evidence that NGS OC somatic screening will identify all germinal point mutations and an indeterminate number of additional pts with exclusive somatic mutations. An ideal correlation needs integration of differenttechniques that may increase complexity, time and cost.

Comparison of risk-reducing surgery in women with BRCA and non-BRCA ovarian cancer susceptibility genes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1547-1547
Author(s):  
Zachary Phillip Schwartz ◽  
Mae Zakhour ◽  
Andrew John Li ◽  
Christine S. Walsh ◽  
Bj Rimel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Susceptibility Genes ◽  
Brca Mutations ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
History Of ◽  
Risk Reducing

1547 Background: Risk reducing gynecologic surgery (RRSO) is standard of care for women with BRCA mutations. The optimal management for women with non-BRCA ovarian cancer susceptibility mutations remains unclear. We sought to characterize the practice patterns for these women at our two institutions. Methods: Women with germline ovarian cancer susceptibility genes who had a RRSO were identified from 1/2000-1/2019 in an IRB approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. Continuous variables were analyzed with Kruskal-Wallis and categorical variables analyzed with chi square and t-tests. Results: 152 BRCA1, 95 BRCA2, and 63 Non-BRCA mutation carriers were identified—50 Lynch (22 MLH1, 13 MSH2, 13 MSH6, 2 PMS2) and 13 Other (6 BRIP1, 2 RAD51C, 5 RAD51D). There was no difference between age at testing, age at RRSO, and interval between testing and RRSO between groups. Genetic counseling was higher in Non-BRCA patients. Family history of ovarian cancer was more common in women with BRCA1 and Other germline mutations compared to BRCA2 and Lynch. Family and personal history of breast cancer was high in all groups except Lynch carriers. Prophylactic mastectomy was seen mostly in BRCA mutation carriers. Concomitant hysterectomy was performed in the majority of women (BRCA1 59%, BRCA2 57%, and Other 62%), with the highest frequency in Lynch carriers (86%, p<.01). Occult cancer was only seen in BRCA mutation carriers: BRCA1 (7%), BRCA2 (2%), Lynch (0%), Other (0%). Conclusions: In this cohort, women with Non-BRCA mutations are managed similarly to women with BRCA mutations. We observed no occult cancers in Non-BRCA patients. The optimal role of surgery as a risk reducing strategy in this group requires further study. [Table: see text]

Real-world treatment patterns of maintenance therapy in platinum-sensitive recurrent epithelial ovarian cancer: Are some patients missing out?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18042-e18042
Author(s):  
Haley Moss ◽  
Angeles Alvarez Secord ◽  
Jessica Perhanidis ◽  
Carol Hawkes
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Active Surveillance ◽  
Real World ◽  
Brca Mutation ◽  
Treatment Patterns ◽  
World Population ◽  
Brca Mutations ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

e18042 Background: The clinical utility of maintenance therapy (MT) for patients with platinum-sensitive recurrent ovarian cancer (PSROC) has been validated in several clinical trials. We assessed real world treatment patterns using a US nationwide electronic health record database. Methods: A retrospective study of patients with PSROC between March 2017 and July 2019 was conducted using the Flatiron Health database. This longitudinal, demographically and geographically diverse de-identified database covers > 2.2 million oncology patients in > 280 cancer clinics. Patients were excluded if second or third line (2L or 3L) platinum-based chemotherapy (PBT) regimens included less than four or more than eight cycles of platinum. Information regarding somatic or germline BRCA mutations and homologous recombination deficiency (HRD) were obtained. Results: 2292 patients with PSROC were identified (had 2L or 3L treatment); 1214 of these received PBT at recurrence; 610 completed the PBT for recurrence on or after March 2017; 351 received 4–8 cycles of PBT; 225 patients had ≥2 months of active surveillance or were receiving MT of PARPi or bevacizumab (B) and were included in this analysis. 183 patients (80%) had BRCA testing and 14 patients (6%) had HRD testing. 46 (20%) had a germline or somatic BRCA mutations (t BRCA), 134 (59%) had a wildtype wt BRCA gene, and 48 (21%) were unknown. Of patients with tBRCA, 63% received a PARP inhibitor (PARPi), 17% received B, 20% received active surveillance. Of patients with wt BRCA, 40% received a PARPi, 24% received B, and 37% received active surveillance. Olaparib was the most commonly used PARPi among tBRCA patients (26%), while niraparib was most commonly used among wt BRCA patients (21%). MT was more common in younger patients, those with a better performance status and with a BRCA mutation. MT use trend increased by 21% during the study period. As PARPi use increased, the use of active surveillance as a post-platinum regimen decreased during the later time periods (Table). Conclusions: In this real world population, the majority of patients with PSROC are receiving maintenance therapy. While genetic testing is improving, universal testing of all patients with ovarian cancer remains the goal. The results provide insight into the shifting treatment patterns for patients with ovarian cancer. [Table: see text]

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