PDF(Pubmed)
Abstract：
UNASSIGNED: Approximately 10% of breast cancer (BC) cases result from hereditary causes. Genetic testing has been widely implemented in BC care to determine hereditary cancer syndromes and personalized medicine. Thus, identification of individuals carrying germline pathogenic variants could be useful to provide appropriate prophylactic or screening measures for each BC subtype, however, there are few formal recommendations for genetic testing in this sense so far. In this study, we assessed rare germline variants in a specific group of genes in order to determine the association with human epidermal growth factor 2 enriched (HER2+) BC phenotype through a systematic review and meta-analysis comparing subtypes overexpressing HER2 with other clinically recognized subtypes of BC. This review was registered with PROSPERO (ID: CRD42023447571).
UNASSIGNED: We conducted an online literature search in PubMed (MEDLINE), Scopus, and EMBASE databases. We included original studies that investigated germline variants in HER2+ BC patients and selected the studies that reported only rare and/or pathogenic germline variants. We assessed the risk of bias and quality of the studies using the Joanna Briggs Institute Critical Appraisal checklists and the Modified Newcastle-Ottawa Scale for Genetic Studies, respectively. Considering hormone receptor and HER2 expression status, we compared gene-based risks initially in HR-HER2-, HR+HER2-, HR+HER2+, and HR-HER2+ groups, conducting separate meta-analyses using the random effects model for each comparison, and within them for each gene.
UNASSIGNED: Of the total 36 studies describing germline variants, 11 studies provided information on the prevalence of variants in the different clinically relevant BC subtypes and allowed comparisons. Germline variants within eight genes showed significant differences when meta-analyzed between the BC groups: BRCA1, BRCA2, TP53, ATM, CHEK2, PALB2, RAD51C, and BARD1. Notably, TP53, ATM, and CHEK2 germline variants were identified as predisposing factors for HER2+ subtypes, whereas BRCA1, BRCA2, PALB2, RAD51C, and BARD1 germline variants were associated with a predisposition to low HER2 expression. Main concerns about bias and quality assessment were the lack of confounding factors control; and comparability or outcome assessment, respectively.
UNASSIGNED: Our findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023447571.
UNASSIGNED: We conducted an online literature search in PubMed (MEDLINE), Scopus, and EMBASE databases. We included original studies that investigated germline variants in HER2+ BC patients and selected the studies that reported only rare and/or pathogenic germline variants. We assessed the risk of bias and quality of the studies using the Joanna Briggs Institute Critical Appraisal checklists and the Modified Newcastle-Ottawa Scale for Genetic Studies, respectively. Considering hormone receptor and HER2 expression status, we compared gene-based risks initially in HR-HER2-, HR+HER2-, HR+HER2+, and HR-HER2+ groups, conducting separate meta-analyses using the random effects model for each comparison, and within them for each gene.
UNASSIGNED: Of the total 36 studies describing germline variants, 11 studies provided information on the prevalence of variants in the different clinically relevant BC subtypes and allowed comparisons. Germline variants within eight genes showed significant differences when meta-analyzed between the BC groups: BRCA1, BRCA2, TP53, ATM, CHEK2, PALB2, RAD51C, and BARD1. Notably, TP53, ATM, and CHEK2 germline variants were identified as predisposing factors for HER2+ subtypes, whereas BRCA1, BRCA2, PALB2, RAD51C, and BARD1 germline variants were associated with a predisposition to low HER2 expression. Main concerns about bias and quality assessment were the lack of confounding factors control; and comparability or outcome assessment, respectively.
UNASSIGNED: Our findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023447571.
摘要：
■大约10％的乳腺癌（BC）病例是由遗传原因引起的。遗传检测已在BC护理中广泛实施，以确定遗传性癌症综合征和个性化医疗。因此，鉴定携带种系致病变异体的个体可用于为每种BC亚型提供适当的预防或筛查措施。然而,到目前为止，很少有正式的基因检测建议。在这项研究中,我们通过系统评价和荟萃分析,比较过表达HER2的亚型与其他临床公认的BC亚型,评估了一组特定基因中的罕见种系变异,以确定与富含人表皮生长因子2(HER2+)BC表型的相关性.这篇评论在PROSPERO注册(ID:CRD42023447571)。
■我们在PubMed（MEDLINE）进行了在线文献检索，Scopus,EMBASE数据库。我们纳入了研究HER2+BC患者种系变异的原始研究，并选择了仅报道罕见和/或致病性种系变异的研究。我们使用JoannaBriggs研究所关键评估清单和改良的Newcastle-Ottawa遗传研究量表评估了偏倚和研究质量的风险。分别。考虑到激素受体和HER2表达状态，我们比较了最初在HR-HER2-中基于基因的风险，HR+HER2-,HR+HER2+,和HR-HER2+组，对每个比较使用随机效应模型进行单独的荟萃分析，并在其中为每个基因。
■在总共36项描述种系变异的研究中，11项研究提供了有关不同临床相关BC亚型中变体患病率的信息，并进行了比较。8个基因内的种系变体在BC组之间进行meta分析时显示出显着差异：BRCA1，BRCA2，TP53，ATM，CHEK2,PALB2,RAD51C,和BARD1。值得注意的是,TP53,ATM,CHEK2种系变异体被鉴定为HER2+亚型的易感因素，而BRCA1，BRCA2，PALB2，RAD51C，和BARD1种系变异与低HER2表达倾向相关。对偏见和质量评估的主要关注是缺乏混杂因素控制；和可比性或结果评估，分别。
■我们的发现强调了种系变异与HER2蛋白和BC亚型差异表达之间的联系。
■https://www.crd.约克。AC.英国/PROSPERO,标识符CRD42023447571。
■我们在PubMed（MEDLINE）进行了在线文献检索，Scopus,EMBASE数据库。我们纳入了研究HER2+BC患者种系变异的原始研究，并选择了仅报道罕见和/或致病性种系变异的研究。我们使用JoannaBriggs研究所关键评估清单和改良的Newcastle-Ottawa遗传研究量表评估了偏倚和研究质量的风险。分别。考虑到激素受体和HER2表达状态，我们比较了最初在HR-HER2-中基于基因的风险，HR+HER2-,HR+HER2+,和HR-HER2+组，对每个比较使用随机效应模型进行单独的荟萃分析，并在其中为每个基因。
■在总共36项描述种系变异的研究中，11项研究提供了有关不同临床相关BC亚型中变体患病率的信息，并进行了比较。8个基因内的种系变体在BC组之间进行meta分析时显示出显着差异：BRCA1，BRCA2，TP53，ATM，CHEK2,PALB2,RAD51C,和BARD1。值得注意的是,TP53,ATM,CHEK2种系变异体被鉴定为HER2+亚型的易感因素，而BRCA1，BRCA2，PALB2，RAD51C，和BARD1种系变异与低HER2表达倾向相关。对偏见和质量评估的主要关注是缺乏混杂因素控制；和可比性或结果评估，分别。
■我们的发现强调了种系变异与HER2蛋白和BC亚型差异表达之间的联系。
■https://www.crd.约克。AC.英国/PROSPERO,标识符CRD42023447571。
