BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breas...BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.展开更多
Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of Califor...Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.展开更多
目的:评估BRCA1/2基因突变状态与卵巢癌患者临床特征的相关性及对预后的影响。方法:选取2017年11月—2022年6月在兰州大学第一医院进行治疗的51例接受BRCA1/2基因检测的卵巢癌患者作为研究对象,根据检测结果分为BRCA1/2突变组(30例)和BR...目的:评估BRCA1/2基因突变状态与卵巢癌患者临床特征的相关性及对预后的影响。方法:选取2017年11月—2022年6月在兰州大学第一医院进行治疗的51例接受BRCA1/2基因检测的卵巢癌患者作为研究对象,根据检测结果分为BRCA1/2突变组(30例)和BRCA1/2正常组(21例)。比较2组患者的临床基线资料、临床病理特征和预后,分析影响BRCA1/2基因突变的卵巢癌患者预后的相关因素。结果:BRCA1/2突变组与BRCA1/2正常组相比,发病年龄、体质量指数(body mass index,BMI)、恶性肿瘤家族史、治疗前糖类抗原125(carbohydrate antigen 125,CA125)及人附睾蛋白4(human epididymis protein 4,HE4)差异均无统计学意义(均P>0.05)。BRCA1/2突变组与BRCA1/2正常组肿瘤分期及淋巴结转移情况比较,差异有统计学意义(P<0.05)。多因素Cox回归分析显示BRCA1/2基因突变不是卵巢癌生存率及无进展生存期的独立预后因素(HR=0.752,95%CI:0.394~1.435,P=0.329)。结论:BRCA1/2基因突变是决定卵巢癌患者临床治疗的重要因素,与肿瘤分期及淋巴结转移情况显著相关,但仍不能确定BRCA1/2基因突变是卵巢癌的独立危险因素。展开更多
文摘BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.
基金supported by a grant from the Nantong City Science and Technology Bureau Project(no.:HS2020005).
文摘Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.
文摘目的:评估BRCA1/2基因突变状态与卵巢癌患者临床特征的相关性及对预后的影响。方法:选取2017年11月—2022年6月在兰州大学第一医院进行治疗的51例接受BRCA1/2基因检测的卵巢癌患者作为研究对象,根据检测结果分为BRCA1/2突变组(30例)和BRCA1/2正常组(21例)。比较2组患者的临床基线资料、临床病理特征和预后,分析影响BRCA1/2基因突变的卵巢癌患者预后的相关因素。结果:BRCA1/2突变组与BRCA1/2正常组相比,发病年龄、体质量指数(body mass index,BMI)、恶性肿瘤家族史、治疗前糖类抗原125(carbohydrate antigen 125,CA125)及人附睾蛋白4(human epididymis protein 4,HE4)差异均无统计学意义(均P>0.05)。BRCA1/2突变组与BRCA1/2正常组肿瘤分期及淋巴结转移情况比较,差异有统计学意义(P<0.05)。多因素Cox回归分析显示BRCA1/2基因突变不是卵巢癌生存率及无进展生存期的独立预后因素(HR=0.752,95%CI:0.394~1.435,P=0.329)。结论:BRCA1/2基因突变是决定卵巢癌患者临床治疗的重要因素,与肿瘤分期及淋巴结转移情况显著相关,但仍不能确定BRCA1/2基因突变是卵巢癌的独立危险因素。
