BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study

Unni, Sudhir; Schauerhamer, Marisa B.; Deka, Rishi; Tyczynski, Jerzy E.; Fernandes, Ancilla W.; Stevens, Vanessa; Brixner, Diana I.; Stenehjem, David D.

doi:10.1186/s13048-016-0227-x

Cited by 10 publications

(7 citation statements)

References 15 publications

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“…The median age at diagnosis was lower than that in other regions: 52 vs 63 years; however, there was no statistically significant difference between BRCAm and BRCAw ( p -value = 0.13) [ 25 ]. There was a greater association of a family history of malignancy and a personal history of cancer with the BRCA mutant patients than in the wild-type patients ( p = 0.02 and p = 0.04, respectively), which has been reported earlier [ 26 ]. However, most cases of OC did not have a positive family history, as noted in earlier studies [ 5 ].…”

Section: Discussionsupporting

confidence: 72%

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

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 72%

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

et al. 2022

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“…EOC lacks significant symptoms in the early stage, leading to poor prognosis, so the biggest challenge of curing EOC is early diagnosis 2. Surgical and adjuvant therapies have limited function in improving the prognosis for advanced EOC, and there is growing evidence that targeted therapy for specific biological factors has greater value 3…”

Section: Introductionmentioning

confidence: 99%

<p><em>ITLN1</em> identified by comprehensive bioinformatic analysis as a hub candidate biological target in human epithelial ovarian cancer</p>

Liu

Liang

et al. 2019

CMAR

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Background Epithelial ovarian cancer (EOC) is a female malignant tumor. Bioinformatics has been widely utilized to analyze genes related to cancer progression. Targeted therapy for specific biological factors has become more valuable. Materials and methods Gene expression profiles of GSE18520 and GSE27651 were downloaded from Gene Expression Omnibus. We used the “limma” package to screen differentially expressed genes (DEGs) between EOC and normal ovarian tissue samples and then used Clusterprofiler to do functional and pathway enrichment analyses. We utilized Search Tool for the Retrieval of Interacting Genes Database to assess protein–protein interaction (PPI) information and the plug-in Molecular Complex Detection to screen hub modules of PPI network in Cytoscape, and then performed functional analysis on the genes in the hub module. Next, we utilized the Weighted Gene Expression Network Analysis package to establish a co-expression network. Validation of the key genes in databases and Gene Expression Profiling Interactive Analysis (GEPIA) were completed. Finally, we used quantitative real-time PCR to validate hub gene expression in clinical tissue samples. Results We analyzed the DEGs (96 samples of EOC tissue and 16 samples of normal ovarian tissue) for functional analysis, which showed that upregulated DEGs were strikingly enriched in phosphate ion binding and the downregulated DEGs were significantly enriched in glycosaminoglycan binding. In the PPI network, CDK1 was screened as the most relevant protein. In the co-expression network, one EOC-related module was identified. For survival analysis, database and clinical sample validation of genes in the turquoise module, we found that ITLN1 was positively correlated with EOC prognosis and had lower level in EOC than in normal tissues, which was consistent with the results predicted in GEPIA. Conclusion In this study, we exhibited the key genes and pathways involved in EOC and speculated that ITLN1 was a tumor suppressor which could be used as a potential biomarker for treating EOC, Gene Expression Omnibus, prognosis.

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“…Several studies have shown that cancers linked to BRCA mutations respond better to platinum-based chemotherapy and to PARP inhibitors and it is well established that BRCA mutation status can inform treatment. An observational study found that there were better survival rates in patients who tested for BRCA mutations and thus availed of therapies known to have better outcomes based on their genetic profiles [ 86 ]. Apart from improving treatment outcomes in patients who test for mutations after developing disease, hereditary screening for genetic BRCA mutations is a useful tool for the prevention of disease in patients with a known risk of developing certain malignancies.…”

Section: Introductionmentioning

confidence: 99%

BRCA mutations in the manifestation and treatment of ovarian cancer

Zhang

Xie

2017

Oncotarget

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BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin. Studies have established that ovarian tumors harboring BRCA mutations have distinct molecular and histo-pathological features that can be exploited for effective, targeted treatment. Deficiencies in DNA repair pathways that arise as a result of BRCA mutations make them hypersensitive to DNA-damaging treatments such as platinum chemotherapy and PARP inhibitors. Different combinations of treatment regimens which have the potential to greatly improve prognosis and disease outcomes are currently being evaluated. However, the issue of developing resistance to these treatments remains unresolved. This review emphasizes unique features of BRCA mutated OC and outlines the lay of the land in terms of diagnosis and treatment, while aiming to unravel the challenges that are part of its management.

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BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer – an observational cohort study

Cited by 10 publications

References 15 publications

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

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

<p><em>ITLN1</em> identified by comprehensive bioinformatic analysis as a hub candidate biological target in human epithelial ovarian cancer</p>

BRCA mutations in the manifestation and treatment of ovarian cancer

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