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HER2 intratumoral heterogeneity is independently associated with distal metastasis and overall survival in HER2-positive breast carcinomas

  • Preclinical study
  • Published:
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Abstract

Purpose

Human epidermal growth factor receptor 2 (HER2) intratumoral heterogeneity (ITH) occurs in a subset of breast cancers. Our recent study revealed it as an independent predictive factor for the response to anti-HER2 neoadjuvant therapy. In this study, we aimed to investigate its association with distal metastasis.

Methods

HER2 ITH was assessed using HER2 gene protein assay (GPA) on whole tissue sections of pretreatment biopsies from a cohort of 158 HER2-positive invasive breast carcinomas and correlated with patients’ clinical follow-up outcomes along with other clinicopathologic characteristics.

Results

Fifty-seven cases (36%) showed HER2 ITH including 19 with genetic, 8 with both genetic and non-genetic, and 30 with non-genetic ITH. Multivariate analysis demonstrated larger tumor size, positive resected lymph node(s), negative PR, and the presence of HER2 ITH were independently associated with distal metastasis. Additionally, multivariate analysis demonstrated larger tumor size and the presence of HER2 ITH were the only independent factors associated with decreased overall survival (death).

Conclusion

The presence of HER2 ITH is an independent factor associated with poor overall survival and increased distal metastasis in HER2-positive breast cancer patients.

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Author information

Author notes

  1. Tiansheng Shen and Hiroaki Nitta have contributed equally.

Authors and Affiliations

  1. Department of Pathology, Wexner Medical Center at The Ohio State University, 410 W. 10th Ave, Columbus, OH, 43210, USA

    Tiansheng Shen, Anil V. Parwani & Zaibo Li

  2. Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ, 85755, USA

    Hiroaki Nitta

  3. Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH, 43210, USA

    Lai Wei

Authors
  1. Tiansheng Shen
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  2. Hiroaki Nitta
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  3. Lai Wei
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  4. Anil V. Parwani
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  5. Zaibo Li
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Contributions

Study design: All. Data collection: TS, HN, AVP, ZL. Data analysis: TS, HN, ZL. Statistical oversight: LW. Manuscript preparation: TS, HN, ZL. Manuscript revision: TS, HN, AVP, ZL. Manuscript approval: All.

Corresponding author

Correspondence to Zaibo Li.

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Conflict of interest

H. Nitta is an employee of Roche Tissue Diagnostics. T. Shen, L. Wei, A. Parwani and Z. Li have no financial relationship to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Research involving human and animal rights

This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual patients included in the study.

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Shen, T., Nitta, H., Wei, L. et al. HER2 intratumoral heterogeneity is independently associated with distal metastasis and overall survival in HER2-positive breast carcinomas. Breast Cancer Res Treat 181, 519–527 (2020). https://doi.org/10.1007/s10549-020-05650-1

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  • DOI: https://doi.org/10.1007/s10549-020-05650-1

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