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. 2022 Apr 1;8(4):1-4.
doi: 10.1001/jamaoncol.2021.7239.

Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue

Aileen I Fernandez  1 , Matthew Liu  1 , Andrew Bellizzi  2 , Jane Brock  3 , Oluwole Fadare  4 , Krisztina Hanley  5 , Malini Harigopal  1 , Julie M Jorns  6 , M Gabriela Kuba  7 , Amy Ly  8 , Mirna Podoll  9 , Kimmie Rabe  10 , Mary Ann Sanders  11 , Kamaljeet Singh  12 , Olivia L Snir  13 , T Rinda Soong  14 , Shi Wei  15 , Hannah Wen  7 , Serena Wong  1 , Esther Yoon  16 , Lajos Pusztai  17 , Emily Reisenbichler  1 , David L Rimm  1   17
Affiliations

Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue

Aileen I Fernandez et al. JAMA Oncol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Snir reported receiving personal fees from Diaceutics PLC outside the submitted work. Dr Wen reported receiving personal fees from AstraZeneca outside the submitted work. Dr Pusztai reported receiving clinical trial support from Seagen, grants from Bristol Myers Squibb, clinical trial support and consultation fees from AstraZeneca and Merck, and personal fees from Roche Genentech, Pfizer, Novartis, Biotheranostics, Athenex, Radius, and Clovis outside the submitted work. Dr Rimm reported receiving grants from Amgen, AstraZeneca, Cepheid, Konica/Minolta, Navigate Biopharma, and NextCure and personal fees from Bristol Myers Squibb, Cell Signaling Technology, Danaher, Merck, NanoString, Odonate, Paige.AI, Roche, and Sanofi outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Distribution of ERBB2 Immunohistochemistry (IHC) Scores in 170 Cases Read by 18 Pathologists/Readers of Whole Tissue Sections in the Yale Cohort
A, Each case (on the x-axis) is shown as the percentage of observers who called the case ERBB2 0 vs ERBB2 1+, 2+, or 3+. B, Each case (on the x-axis) is shown as the percentage of observers who called the case ERBB2 3+ vs ERBB2 0, 1+, or 2+.
See this image and copyright information in PMC

Comment in

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