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HER2 testing in breast cancers: comparison of assays and interpretation using ASCO/CAP 2013 and 2018 guidelines

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Abstract

Purpose

HER2 overexpression and gene amplification are routinely tested by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. In addition, HER2 mRNA expression is also tested by the Oncotype DX assay. Discordance between laboratories among the different assays remains a problem. To improve the routine HER2 reporting, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) updated their guidelines in 2018. Our study will compare concordance of HER2 status by IHC and FISH using ASCO/CAP 2013 and 2018 guidelines with Oncotype DX.

Methods

We retrospectively reviewed 657 estrogen receptor positive primary breast cancer cases with available Oncotype DX tests between 2011 and 2018. Medical records were reviewed for HER2 results by IHC, FISH, and Oncotype DX. The HER2 results by different assays and between 2013 and 2018 guidelines were compared.

Results

Of the 657 cases, 280 were tested by IHC, FISH, and Oncotype DX. HER2-equivocal cases by IHC 2013 guidelines were all negative (67/67, 100%) by FISH 2018 guidelines and by Oncotype DX. HER2-equivocal cases by FISH 2013 guidelines were all negative (16/16, 100%) by FISH 2018 guidelines, while 15/16 (93.8%) negative and 1/16 (6.2%) equivocal by Oncotype DX. The HER2-equivocal and HER2-negative groups were similar in age, gender, histology, grade, and Ki67 score.

Conclusions

HER2 concordance was highest between Oncotype DX (99.6%) and FISH per 2018 guidelines. This suggests that the ASCO/CAP 2018 guidelines improved the accurate stratification of HER2-equivocal cases.

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Data availability

The datasets generated during the current study are not publicly available due to individual privacy but are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Dawn Chalaire from the Department of Scientific Publications, at The University of Texas MD Anderson Cancer Center for her assistance in editing this document and Kim-Anh Vu from the Department of Pathology for her help with graphic images.

Funding

This work was supported in part by the NIH/NCI Cancer Center Support Grant (P30 CA016672) used for the Biostatistics Resource Group.

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Author notes

  1. Lauren E. McLemore

    Present address: Department of Pathology, University of Colorado, Denver, CO, USA

  2. Lauren E. McLemore and Constance T. Albarracin contributed equally to this work and share co-first authorship.

Authors and Affiliations

  1. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 085, G1.3617B, Houston, TX, 77030, USA

    Lauren E. McLemore, Constance T. Albarracin, Yun Wu, Isaiah Yim, Kevin Lin, Nour Sneige & Hui Chen

  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Stephen K. Gruschkus & Roland L. Bassett Jr

  3. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA

    Sagar Dhamne

  4. Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Isabelle Bedrosian

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Contributions

HC and CTA conceived the study. LM, CTA, NS, HC were involved in the design of the study. SD, IY, KL and HC were involved in the acquisition of data. CTA and HC were involved in study supervision. LM, CTA, SKG, RLB, YW and HC were involved in the analysis and interpretation of data. LM, CTA, HC and NS drafted the manuscript. All authors critically reviewed and approved the manuscript before submission.

Corresponding author

Correspondence to Hui Chen.

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All authors declare they have no conflicts of interest.

Ethical approval

This project was approved by the Institutional Review Board of the M.D. Anderson Cancer (PA18-0796).

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McLemore, L.E., Albarracin, C.T., Gruschkus, S.K. et al. HER2 testing in breast cancers: comparison of assays and interpretation using ASCO/CAP 2013 and 2018 guidelines. Breast Cancer Res Treat 187, 95–104 (2021). https://doi.org/10.1007/s10549-021-06208-5

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