{"entity":{"id":"paper-fernandez-jama-oncol","kind":"paper","name":"Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue","aka":[],"tldr":"Paper cited by one bottleneck page and 17 idea pages, indexed on Europe PMC as PubMed record 35113160 and published in JAMA Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Trastuzumab deruxtecan (T-DXd) has shown efficacy in patients with breast cancer with ERBB2 immunohistochemistry (IHC) scores of 1+ or 2+ but not 0 as read in central pathology laboratories. The drug is currently being tested in large randomized clinical trials with registration intent for this patient population.\n\nObjective: To determine the suitability of the current standard ERBB2 IHC assays to select patients with low ERBB2 positivity for treatment with T-DXd.\n\nDesign and setting: Assessment of data from College of American Pathologists surveys and assessment of analytic data from a Yale University-based study of concordance of 18 pathologists reading 170 breast cancer biopsies.\n\nResults: The total survey data set included scores over 2 years from 1391 to 1452 laboratories of 40 ERBB2 cores from each laboratory (20 cores twice a year for a total of 80). College of American Pathologists surveys show that 19% of cases read by the laboratories generate results with less than or equal to 70% concordance for IHC ERBB2 score 0 vs 1+. When 18 pathologists read the scanned slides from a selected set of breast cancer biopsies using a 4-point scale, there was only 26% concordance between 0 and 1+ compared with 58% concordance between 2+ and 3+.\n\nConclusions and relevance: In this study using a current standard ERBB2 IHC assay, the scoring accuracy for ERBB2 IHC in the low range (0 and 1+) was poor. This inaccuracy in the real world could lead to misassignment of many patients for treatment with T-DXd.\n\nIndexed on Europe PMC as PubMed record 35113160 (DOI 10.1001/jamaoncol.2021.7239). Matched by DOI alone: one bottleneck page and 17 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2022","url":"https://doi.org/10.1001/jamaoncol.2021.7239"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35113160/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35113160"}],"tags":["europepmc-ingest"],"related":["b-biomarker-validation","idea-tr2-prospective-retrospective-path","idea-tr2-hrd-functional-standard","idea-moon-biomarker-validation-utility","idea-tr2-label-assay-concordance","idea-tr2-biomarker-evidence-grading","idea-tr2-cutpoint-lock","idea-tr2-positivity-rate-surveillance","idea-tr2-pdl1-digital-calibration","idea-tr2-biomarker-cwe","idea-tr2-biomarker-study-registry","idea-tr2-biomarker-negative-arms","idea-tr2-bicr-discordance-public","idea-tr2-preanalytics-in-report","idea-tr2-cdx-mutual-recognition","idea-tr2-spatial-biomarker-standards","idea-tr2-marker-stratified-default","idea-tr2-ai-cdx-change-control"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2022,"doi":"10.1001/jamaoncol.2021.7239","pmid":"35113160","authors":"Fernandez AI, Liu M, Bellizzi A, et al.","paperType":"rct","findings":[],"whatItMeans":"One bottleneck page and 17 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-fernandez-jama-oncol/","neighbours":{"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"idea":[{"id":"idea-tr2-prospective-retrospective-path","kind":"idea","name":"A formal regulatory route for validating a biomarker on archived trial samples","route":"/ideas/idea-tr2-prospective-retrospective-path/"},{"id":"idea-tr2-hrd-functional-standard","kind":"idea","name":"A functional test for homologous recombination deficiency validated across laboratories","route":"/ideas/idea-tr2-hrd-functional-standard/"},{"id":"idea-moon-biomarker-validation-utility","kind":"idea","name":"A public biomarker validation utility with pre-diagnostic biobanks and blinded testing","route":"/ideas/idea-moon-biomarker-validation-utility/"},{"id":"idea-tr2-label-assay-concordance","kind":"idea","name":"Drug labels must state which biomarker assays were validated and how they compare","route":"/ideas/idea-tr2-label-assay-concordance/"},{"id":"idea-tr2-biomarker-evidence-grading","kind":"idea","name":"Label every biomarker claim with an evidence phase, like drugs","route":"/ideas/idea-tr2-biomarker-evidence-grading/"},{"id":"idea-tr2-cutpoint-lock","kind":"idea","name":"Lock the biomarker cut-off before phase 3, and publish it","route":"/ideas/idea-tr2-cutpoint-lock/"},{"id":"idea-tr2-positivity-rate-surveillance","kind":"idea","name":"Monitor biomarker positivity rates across labs in real time to catch assay drift","route":"/ideas/idea-tr2-positivity-rate-surveillance/"},{"id":"idea-tr2-pdl1-digital-calibration","kind":"idea","name":"One digital PD-L1 scale that maps across all the competing assays","route":"/ideas/idea-tr2-pdl1-digital-calibration/"},{"id":"idea-tr2-biomarker-cwe","kind":"idea","name":"Pay for new biomarker tests only while evidence of clinical utility is being collected","route":"/ideas/idea-tr2-biomarker-cwe/"},{"id":"idea-tr2-biomarker-study-registry","kind":"idea","name":"Pre-register biomarker validation studies the way trials are registered","route":"/ideas/idea-tr2-biomarker-study-registry/"},{"id":"idea-tr2-bicr-discordance-public","kind":"idea","name":"Publish the disagreement between trial doctors and independent reviewers for every trial","route":"/ideas/idea-tr2-bicr-discordance-public/"},{"id":"idea-tr2-biomarker-negative-arms","kind":"idea","name":"Randomised trials to test whether biomarker-negative patients really do not benefit","route":"/ideas/idea-tr2-biomarker-negative-arms/"},{"id":"idea-tr2-preanalytics-in-report","kind":"idea","name":"Record how long tissue waited before fixation in every pathology report","route":"/ideas/idea-tr2-preanalytics-in-report/"},{"id":"idea-tr2-cdx-mutual-recognition","kind":"idea","name":"Regulators recognise each other's companion diagnostic approvals","route":"/ideas/idea-tr2-cdx-mutual-recognition/"},{"id":"idea-tr2-spatial-biomarker-standards","kind":"idea","name":"Standards for spatial and multiplex tissue biomarkers before they reach the clinic","route":"/ideas/idea-tr2-spatial-biomarker-standards/"},{"id":"idea-tr2-marker-stratified-default","kind":"idea","name":"Test the drug in biomarker-negative patients too, so the biomarker can be validated","route":"/ideas/idea-tr2-marker-stratified-default/"},{"id":"idea-tr2-ai-cdx-change-control","kind":"idea","name":"Version control and locked reference sets for AI algorithms used as companion diagnostics","route":"/ideas/idea-tr2-ai-cdx-change-control/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}]}}