SynthesisFrontiers in oncology2024
Germline rare variants in HER2-positive breast cancer predisposition: a systematic review and meta-analysis.
Synthesis in Frontiers in oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Article
- Breast Cancer: Epidemiology, Molecular Classification, Diagnostics and Evolving Treatment Paradigms.Molecules (Basel, Switzerland) · 2026Review
- Ipsilateral Breast Carcinoma Recurrence: True Recurrence or New Primary? A Clinicopathologic and Molecular Study.The American journal of surgical pathology · 2025Article
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Authors and funding
10 authors.
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Abstract
Introduction: 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). Methods: 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. Results: 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: Discussion: Our findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023447571.
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