ArticleBMC medicine2022
HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 3 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 3 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis.World journal of surgical oncology · 2024Pooled it
- Prognostic value of HER2-low status in breast cancer: a systematic review and meta-analysis.ESMO open · 2023Pooled it
- Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- HER2-Low Versus HER2-Zero Breast Cancer in the Neoadjuvant Setting: Pathological Complete Response and Exploratory Survival Outcomes in a Single-Center Cohort.Medicina (Kaunas, Lithuania) · 2026Article
- Clinicopathological characteristics across the HER2 expression spectrum in invasive breast carcinoma of no special type: a single-centre retrospective study.Diagnostic pathology · 2026Article
- Pathogenic germline variants associated with different HER2 expression among breast cancer patients.Discover oncology · 2026Article
- Molecular characteristics and prognosis of triple negative breast cancer stratified by HER2 status.Chinese medical journal · 2026Article
- Addressing the Challenges in the Identification of HER2-Low and Ultralow Breast Cancer in Asia: A Delphi Consensus.Advances in therapy · 2026Article
- Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- HER2-low status in breast cancer: clinicopathological factors and prognostic value.Archives of medical science : AMS · 2026Article
- Prognostic value of RecurIndex in differentiating HER2-low from HER2-negative early-stage breast cancer: a comprehensive clinicopathologic and molecular analysis in Chinese patients.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Article
- HER2-Low Breast Cancer at the Interface of Pathology and Technology: Toward Precision Management.Biomedicines · 2025Review
- Clinical characteristics and prognostic impact of HER2-ultralow breast cancer and tumor-infiltrating lymphocytes (TILs).BMC cancer · 2025Article
- Interplay Between MicroRNAs and Breast Cancer Therapies: Personalized Therapeutic Potential for HER2-Low Breast Cancer.Cancers · 2025Review
- Differences in Sentinel lymph node biopsy outcomes and prognosis between HER2-low and HER2-zero breast cancer.BMC cancer · 2025Article
- Advancing breast cancer research through real-world data from the Singapore Joint Breast Cancer Registry.ESMO real world data and digital oncology · 2025Article
- Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy.Medicina (Kaunas, Lithuania) · 2025Article
- A Comprehensive Review of Deep Learning Applications with Multi-Omics Data in Cancer Research.Genes · 2025Review
- Deciphering the role ofJournal of translational internal medicine · 2025Article
- Prognostic difference between early breast cancer patients with HER2 low and HER2 zero status.NPJ breast cancer · 2025Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact of low expression of HER2 on survival outcomes in HER2-negative non-metastatic breast cancer (BC).
methodsPatients with HER2-negative non-metastatic BC from 6 centres within the Asian Breast Cancer Cooperative Group (ABCCG) (n = 28,280) were analysed. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+ and in situ hybridization non-amplified (ISH-) and HER2-zero as IHC 0. Relapse-free survival (RFS) and overall survival (OS) by hormone receptor status and HER2 IHC 0, 1+ and 2+ ISH- status were the main outcomes. A combined TCGA-BRCA and METABRIC cohort (n = 1967) was also analysed to explore the association between HER2 expression, ERBB2 copy number variation (CNV) status and RFS.
resultsABCCG cohort median follow-up was 6.6 years; there were 12,260 (43.4%) HER2-low BC and 16,020 (56.6%) HER2-zero BC. The outcomes were better in HER2-low BC than in HER2-zero BC (RFS: centre-adjusted hazard ratio (HR) 0.88, 95% CI 0.82-0.93, P < 0.001; OS: centre-adjusted HR 0.82, 95% CI 0.76-0.89, P < 0.001). On multivariable analysis, HER2-low status was prognostic (RFS: HR 0.90, 95% CI 0.85-0.96, P = 0.002; OS: HR 0.86, 95% CI 0.79-0.93, P < 0.001). These differences remained significant in hormone receptor-positive tumours and for OS in hormone receptor-negative tumours. Superior outcomes were observed for HER2 IHC1+ BC versus HER2-zero BC (RFS: HR 0.89, 95% CI 0.83-0.96, P = 0.001; OS: HR 0.85, 95% CI 0.78-0.93, P = 0.001). No significant differences were seen between HER2 IHC2+ ISH- and HER2-zero BCs. In the TCGA-BRCA and METABRIC cohorts, ERBB2 CNV status was an independent RFS prognostic factor (neutral versus non-neutral HR 0.71, 95% CI 0.59-0.86, P < 0.001); no differences in RFS by ERBB2 mRNA expression levels were found.
conclusionsHER2-low BC had a superior prognosis compared to HER2-zero BC in the non-metastatic setting, though absolute differences were modest and driven by HER2 IHC 1+ BC. ERBB2 CNV merits further investigation in HER2-negative BC.
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