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HER2 intratumoral heterogeneity is independently associated with incomplete response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma

  • Preclinical study
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Abstract

Purpose

Anti-HER2 neoadjuvant chemotherapy has been widely used in HER2-positive breast cancer patients; however, pathologic complete response (pCR) is achieved in only 40–50% of patients. The aim of this study was to investigate the association of HER2 intratumoral heterogeneity (ITH) with response to anti-HER2 neoadjuvant chemotherapy.

Methods

Assessment of HER2 ITH was performed on whole tissue sections of pre-treatment samples from a cohort of 64 invasive breast carcinoma cases originally considered positive for HER2 and treated with anti-HER2 neoadjuvant chemotherapy. Both HER2 gene signal and protein expression were simultaneously evaluated by means of a single-slide dual assay, designated as a HER2 gene-protein assay (GPA). HER2 GPA was carried out as well on surgical resection tissues from 25 cases with incomplete therapeutic response.

Results

Nineteen of 64 cases (30%) showed HER2 ITH. Significantly more cases with HER2 ITH were found in the incomplete response group (56%, 14/25) than in the pCR group (13%, 5/39). Patients without ITH detectable by GPA had a 76% pCR outcome (34/45), as compared to 26% (5/19) for those with detectable ITH. Multivariate analysis demonstrated HER2 ITH, progesterone receptor positivity, and relatively low HER2/chromosome 17 centromere ratio to be significantly associated with incomplete response.

Conclusions

HER2 ITH analyses conducted with GPA method revealed that HER2 ITH is an independent factor predicting incomplete response to anti-HER2 neoadjuvant chemotherapy.

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Funding

This study is partly supported by The Ohio State University FAME program.

Author information

Author notes

  1. Yanjun Hou and Hiroaki Nitta contributed equally to this work.

Authors and Affiliations

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

    Yanjun Hou, Anil V. Parwani & Zaibo Li

  2. Ventana Medical Systems, Inc., 1910 E. Innovation Park Drive, Tucson, AZ, 85755, USA

    Hiroaki Nitta, Peter M. Banks & Bryce Portier

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

    Lai Wei

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  1. Yanjun Hou
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Contributions

Study design: All. Data collection: YH, HN, PB, BP, ZL. Data analysis: YH, HN, ZL. Statistical oversight: LW. Manuscript preparation: YH, HN, ZL. Manuscript revision: HN, PMB, ZL, BP. Manuscript approval: All.

Corresponding author

Correspondence to Zaibo Li.

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Conflict of interest

Y. Hou, L. Wei, A. Parwani, and Z. Li have no financial relationship to disclose. H. Nitta, B. Portier, and P.M. Banks are employees of Ventana Medical Systems, Inc.

Ethical approval

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

Informed consent

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

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Hou, Y., Nitta, H., Wei, L. et al. HER2 intratumoral heterogeneity is independently associated with incomplete response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma. Breast Cancer Res Treat 166, 447–457 (2017). https://doi.org/10.1007/s10549-017-4453-8

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  • DOI: https://doi.org/10.1007/s10549-017-4453-8

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