Germline mutations in Black patients with ovarian, fallopian tube and primary peritoneal carcinomas

Somasegar, Sahana; Weiss, Arielle S.; Norquist, Barbara M.; Khasnavis, Nithisha; Radke, Marc R.; Manhardt, Enna; Pennil, Christopher C.; Pennington, Kathryn P.; Eckert, Mark A.; Chryplewicz, Agnieszka; Lengyel, Ernst; Swisher, Elizabeth M.

doi:10.1016/j.ygyno.2021.08.017

Cited by 7 publications

(11 citation statements)

References 22 publications

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“…Among these included articles, 50 studies 6,7,9–12,18–61 evaluated the relationship between patients with BRCAms and the clinical features of ovarian cancer, and 22 studies 6,7,9,11,12,21,28,32,38–40,44,45,48,49,52,53,58–60,62,63 evaluated the relationship between patients with BRCAms and surgical outcomes. Also, 48 studies ,6–12,18,21,26–30,32–41,44–49,52–54,57–71 evaluated the relationship between BRCAms and the prognosis of ovarian cancer. The quality assessment showed that the NOS score of each study was not less than 7, indicating that the methodological quality was generally good.…”

Section: Resultsmentioning

confidence: 99%

“…Among these included articles, 50 studies 6,7,9-12,18-61 evaluated the relationship between patients with BRCAms and the clinical features of ovarian cancer, and 22 studies 6,7,9,11,12,21,28,32,[38][39][40]44,45,48,49,52,53,[58][59][60]62,63 evaluated the relationship between patients with BRCAms and surgical outcomes. Also, 48 studies , [6][7][8][9][10][11][12]18,21,[26][27][28][29][30][32][33][34][35][36][37][38][39][40][41][44][45][46][47]…”

Section: Discussionmentioning

confidence: 99%

“…Twenty-two studies 6,7,9,11,12,21,28,32,[38][39][40]44,45,48,49,52,53,[58][59][60]62,63 provided a comparison of surgical outcomes between BRCAm carriers and noncarriers. Satisfactory tumor cell reduction was determined according to the size of residual tumor lesions during tumor reduction, the diameter of the tumors measured <1 cm was satisfactory, and a diameter >1 cm was unsatisfactory.…”

Section: The Association Between the Presence Of Brcams And Surgical ...mentioning

confidence: 99%

“…Thirty-three studies [6][7][8][9][10][11][12]18,[27][28][29][32][33][34][35][36][37][38][39][40][41][46][47][48]52,54,57,60,63,65,66,68,69 provided OS data of patients with BRCA1/BRCA2 mutations. Heterogeneity was observed among the 33 studies (I 2 = 50.3%); therefore, a random effects model was used.…”

Section: Meta-analysis Of Brca1/brca2 Mutationsmentioning

confidence: 99%

“…The analysis revealed a significant OS advantage in ovarian cancer patients with BRCA1/2 mutations (HR = 0.65; 95% CI: 0.59, 0.73; p < 0.001) (Figure 3a). Twenty-three studies [6][7][8]11,12,18,21,32,[35][36][37][38]40,44,46,49,[52][53][54]60,63,65,68 provided data with respect to patients' PFS. A random effects model was used because of significant heterogeneity (I 2 = 54.8%).…”

Section: Meta-analysis Of Brca1/brca2 Mutationsmentioning

confidence: 99%

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Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis

Wang

Ren

et al. 2022

J of Obstet and Gynaecol

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Aim This meta‐analysis was conducted to evaluate the impact of BRCA mutations on survival outcomes of ovarian cancer patients and assess whether the BRCA status was an independent predictor of complete cytoreduction. Methods We searched the PubMed, Cochrane, EMBASE, Scopus, Web of Science, and Google Scholar databases for studies that evaluated the associations among BRCA mutations, ovarian cancer survival and surgical cytoreduction before August 2021 based on specific inclusion and exclusion criteria. Results We identified 61 articles that compared the clinical features, survival outcomes, and optimal surgical cytoreduction rates between BRCA‐positive patients and BRCA‐negative patients. The results showed that BRCA mutation carriers were diagnosed with ovarian cancer at a younger age than the age at which nonmutation carriers were diagnosed. In addition, BRCA mutation carriers were more likely to be in the International Federation of Gynecology and Obstetrics (FIGO) stage III‐IV, and the pathological grade was commonly grade 3. The pathological type of BRCA mutation carriers was more likely to be high‐grade serous carcinoma. Patients with BRCA mutations had higher response rates to platinum‐based chemotherapy than the noncarriers. However, patients in both groups had equivalent rates of surgical cytoreduction, and BRCA‐positive patients had longer overall survival (OS) time (HR = 0.65; 95% confidence interval [CI]: 0.59, 0.73; p < 0.001) and longer progression‐free survival (PFS) (HR = 0.72; 95% CI: 0.63, 0.82; p < 0.001). Conclusion BRCA mutations appear to be associated with improved OS and PFS in patients with ovarian cancer. However, we did not find any difference in the surgical resection rate between participants in the two groups.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: The Association Between the Presence Of Brcams And Surgical ...mentioning

confidence: 99%

Section: Meta-analysis Of Brca1/brca2 Mutationsmentioning

confidence: 99%

Section: Meta-analysis Of Brca1/brca2 Mutationsmentioning

confidence: 99%

See 3 more Smart Citations

Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis

Wang

Ren

et al. 2022

J of Obstet and Gynaecol

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BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer

Richau,

Scherer,

Matta

et al. 2024

Cancer Medicine

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BackgroundApproximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high‐grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss‐of‐function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression‐free survival and overall survival.MethodsThe study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2.ResultsA total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression‐free survival.ConclusionFrequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non‐functional or non‐functional somatic variants, while eight 14.2% presented likely non‐functional or non‐functional somatic variants in BRCA1 or BRCA2.

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Prevalence and clinical implications of germline mutations among Jordanian patients with ovarian cancer. The Jordanian exploratory cancer genetics (Jo‐ECAG) ovarian study

Abdel‐Razeq

Al-Azzam

Elemian

et al. 2022

Molec Gen & Gen Med

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Background Ovarian cancer is one of the most common gynecological malignancies. Due to the absence of effective screening methods, ovarian cancer is usually diagnosed at late stages. Patients with pathogenic and likely‐pathogenic germline variants (PGVs) in BRCA1 or BRCA2 harbor elevated risk of developing both ovarian and breast cancers. Identifying PGVs may help in both cancer prevention and active disease treatment. Worldwide prevalence of PGVs varies and the matter is poorly addressed among Arab patients. Methods Patients with epithelial ovarian, fallopian tube or primary peritoneal cancers were offered the universal 20 or 84‐multi‐gene panel testing as per standard guidelines. Cascade family screening was also offered to all first and second‐degree relatives of PGV positive patients. Genetic testing was done at a referral lab using a next generation sequencing (NGS)‐based platform. Results During the study period, 152 patients, median age (range): 50 (18–79) years old, were tested. The majority ( n = 100, 65.8%) had high‐grade serous carcinoma, and 106 patients (69.7%) had metastatic disease at presentation. In total, 38 (25.0%) had PGVs, while 47 (30.9%) others had variants of uncertain significance (VUS). PGVs were mostly in BRCA1 ( n = 21, 13.8%) and in BRCA2 ( n = 12, 7.9%), while 6 (3.9%) others had PGVs in non‐ BRCA1/2 genes . PGV rates were significantly higher among 15 patients with a positive family history of ovarian cancer (60.0%, p = .022) and among 52 patients with a positive family history of breast cancer (40.4%, p = .017). Conclusions PGVs are common among Jordanian women with ovarian cancer, and mostly occur in BRCA1/2 . Given its clinical impact on disease prevention and precision therapy, universal testing should be routinely offered.

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Germline mutations in Black patients with ovarian, fallopian tube and primary peritoneal carcinomas

Cited by 7 publications

References 22 publications

Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis

Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis

BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer

Prevalence and clinical implications of germline mutations among Jordanian patients with ovarian cancer. The Jordanian exploratory cancer genetics (Jo‐ECAG) ovarian study

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