ArticleClinical chemistry2021
Quantification of Human Epidermal Growth Factor Receptor 2 by Immunopeptide Enrichment and Targeted Mass Spectrometry in Formalin-Fixed Paraffin-Embedded and Frozen Breast Cancer Tissues.
Article in Clinical chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Trastuzumab Deruxtecan for HER2-Low Metastatic Breast Cancer: Practical Considerations for Medical Oncologists and Pathologists in Australia.Asia-Pacific journal of clinical oncology · 2026Review
- Advances in Targeted Therapy for Human Epidermal Growth Factor Receptor 2-Low Tumors: From Trastuzumab to Antibody-Drug Conjugates.World journal of oncology · 2026Review
- Bridging practice and precision: a quantitative HER2 protein assay ready for clinical use in guiding trastuzumab deruxtecan therapy.Frontiers in oncology · 2026Article
- BE screen reveals METTL3 S2 dephosphorylation sensitizes gastric cancer cells to oxaliplatin by interfering METTL3-eIF3H interaction.Science advances · 2025Article
- Novel treatment approaches utilizing antibody-drug conjugates in breast cancer.NPJ breast cancer · 2025Review
- Exploring the heterogeneity of HER2 gene status and expression in non-positive breast cancer patients: insights from immunohistochemistry and fluorescence in situ hybridization.Diagnostic pathology · 2025Article
- Breaking the dichotomy of HER2: highlighting the flaws of simplifying variables.Frontiers in oncology · 2025Article
- Data-Independent Acquisition: A Milestone and Prospect in Clinical Mass Spectrometry-Based Proteomics.Molecular & cellular proteomics : MCP · 2024Review
- Immunohistochemical assessment of HER2 low breast cancer: interobserver reproducibility and correlation with digital image analysis.Breast cancer research and treatment · 2024Article
- Kinase inhibitor pulldown assay (KiP) for clinical proteomics.Clinical proteomics · 2024Article
- Article
- Antibody-Drug Conjugates in Breast Cancer: A Comprehensive Review of How to Selectively Deliver Payloads.Breast cancer (Dove Medical Press) · 2024Review
- High inter-laboratory variability in the assessment of HER2-low breast cancer: a national registry study on 50,714 Danish patients.Breast cancer research : BCR · 2023Article
- Clinical Proteomics for Solid Organ Tissues.Molecular & cellular proteomics : MCP · 2023Article
- The Breast Cancer Proteome and Precision Oncology.Cold Spring Harbor perspectives in medicine · 2023Review
- Article
- Deciphering Phenotypes from Protein Biomarkers for Translational Research with PIPER.Journal of proteome research · 2023Article
- Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety.Cancer discovery · 2023Article
- HER2-Low Breast Cancer: Current Landscape and Future Prospects.Breast cancer (Dove Medical Press) · 2023Review
- A multiplexed assay for quantifying immunomodulatory proteins supports correlative studies in immunotherapy clinical trials.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundConventional HER2-targeting therapies improve outcomes for patients with HER2-positive breast cancer (BC), defined as tumors showing HER2 protein overexpression by immunohistochemistry and/or ERBB2 gene amplification determined by in situ hybridization (ISH). Emerging HER2-targeting compounds show benefit in some patients with neither HER2 protein overexpression nor ERBB2 gene amplification, creating a need for new assays to select HER2-low tumors for treatment with these compounds. We evaluated the analytical performance of a targeted mass spectrometry-based assay for quantifying HER2 protein in formalin-fixed paraffin-embedded (FFPE) and frozen BC biopsies.
methodsWe used immunoaffinity-enrichment coupled to multiple reaction monitoring-mass spectrometry (immuno-MRM-MS) to quantify HER2 protein (as peptide GLQSLPTHDPSPLQR) in 96 frozen and 119 FFPE BC biopsies. We characterized linearity, lower limit of quantification (LLOQ), and intra- and inter-day variation of the assay in frozen and FFPE tissue matrices. We determined concordance between HER2 immuno-MRM-MS and predicate immunohistochemistry and ISH assays and examined the benefit of multiplexing the assay to include proteins expressed in tumor subcompartments (e.g., stroma, adipose, lymphocytes, epithelium) to account for tissue heterogeneity.
resultsHER2 immuno-MRM-MS assay linearity was ≥103, assay coefficient of variation was 7.8% (FFPE) and 5.9% (frozen) for spiked-in analyte, and 7.7% (FFPE) and 7.9% (frozen) for endogenous measurements. Immuno-MRM-MS-based HER2 measurements strongly correlated with predicate assay HER2 determinations, and concordance was improved by normalizing to glyceraldehyde-3-phosphate dehydrogenase. HER2 was quantified above the LLOQ in all tumors.
conclusionsImmuno-MRM-MS can be used to quantify HER2 in FFPE and frozen BC biopsies, even at low HER2 expression levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.