Examination of low ERBB2 protein expression in breast cancer tissue Journal Article
| Authors: | Fernandez, A. I.; Liu, M.; Bellizzi, A.; Brock, J.; Fadare, O.; Hanley, K.; Harigopal, M.; Jorns, J. M.; Kuba, M. G.; Ly, A.; Podoll, M.; Rabe, K.; Sanders, M. A.; Singh, K.; Snir, O. L.; Soong, T. R.; Wei, S.; Wen, H.; Wong, S.; Yoon, E.; Pusztai, L.; Reisenbichler, E.; Rimm, D. L. |
| Article Title: | Examination of low ERBB2 protein expression in breast cancer tissue |
| Abstract: | This study determines the suitability of the current standard ERBB2 immunohistochemistry assays to select patients with low ERBB2 positivity for treatment with trastuzumab deruxtecan. Key Points: Question: Do standard ERBB2 assays accurately separate 0 from 1+ as required by the companion diagnostic test being used in current clinical trials for trastuzumab deruxtecan? Findings: In this study of data from approximately 1400 laboratories around the world, less than 70% interrater agreement was found between ERBB2 scores of 0 and 1+ on 15 of 80 College of American Pathologists survey cases. A separate cohort suggests that this difference appears to be a function of pathologist reader discordance. Meaning: Use of the current ERBB2 assays as a companion diagnostic test for trastuzumab deruxtecan may result in misassignment of patients for treatment. 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. Objective: To determine the suitability of the current standard ERBB2 IHC assays to select patients with low ERBB2 positivity for treatment with T-DXd. Design 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. Results: 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+. Conclusions 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. |
| Journal Title: | JAMA Oncology |
| Volume: | 8 |
| Issue: | 4 |
| ISSN: | 2374-2437 |
| Publisher: | American Medical Association |
| Date Published: | 2022-04-01 |
| Language: | English |
| DOI: | 10.1001/jamaoncol.2021.7239 |
| PROVIDER: | EBSCOhost |
| PROVIDER: | cinahl |
| PMCID: | PMC8814969 |
| PUBMED: | 35113160 |
| DOI/URL: | |
| Notes: | Accession Number: 156475582 -- Entry Date: In Process -- Revision Date: 20220426 -- Publication Type: Article -- Journal Subset: Peer Reviewed; USA. -- Source: Cinahl |
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