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The expression and prognostic role of EBP1 and relationship with AR in HER2+ breast cancer

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Abstract

Human epidermal growth factor receptor (HER)-2 positive (HER2+) breast cancer (BC) has a poor survival rate and is more aggressive in nature. HER2-targeting agents could be beneficial for patients with HER2+ BC. In addition, targeted therapy and chemotherapy have been successfully used. However, a few patients are resistant to treatment. ErbB3 binding protein 1 (EBP1) binds to HER3 and inhibits the proliferation and invasive potential of tumor cells. However, its role in HER2+ BC has not been demonstrated. In this study, we aimed to analyze the relationship between androgen receptor (AR) and EBP1 expression in HER2+ BC. A total of 282 cases (140 cases of HER2+ invasive BC and 142 HER2-negative invasive BC) were included in this study. We performed immunohistochemistry (IHC) to analyze the expression of AR and EBP1; thereafter, we evaluated the relationship between these two biomarkers and estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki67 expression, and other clinicopathological parameters. Of the HER2+ cases, 67 (47.9%) showed high expression of EBP1 (EBP1high) and 73 (52.1%) showed low/no expression of EBP1 (EBP1low/no). EBP1 expression was correlated with AR expression, histological grade, and lymphatic metastasis (p < 0.001, < 0.001, and 0.013, respectively). Kaplan–Meier analysis revealed that AR+ and EBP1low/no group had poorer overall survival (OS) and disease-free survival (DFS) compared with other groups (AR− and EBP1low/no, AR+ and EBP1high, and AR− and EBP1high). AR+ and EBP1low/no expression were independent prognostic factors for OS and DFS in HER2+ BC. This study showed the clinicopathological role of EBP1 and AR in HER2+ BC. Targeting EBP1 may be an effective treatment strategy for patients with AR+ HER2+ BC.

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Funding

This work was funded by the National Natural Science Foundation of China (grant number: 81470119) and the Tianjin Municipal Science and the Technology Commission Research Fund (grant number: 15JCYBJC27800).

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Authors and Affiliations

  1. Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Jing Liu, Cong Xu, Danni Xu, Lu Cao, Huiqin Xue, Qingxiang Meng & Yun Niu

  2. National Clinical Research Center for Cancer,Tianjin Medical University Cancer Institute and Hospital, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, China

    Jing Liu, Cong Xu, Danni Xu, Lu Cao, Huiqin Xue, Qingxiang Meng & Yun Niu

  3. Key Laboratory of Cancer Prevention and Therapy,Tianjin, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, Tianjin, China

    Jing Liu, Cong Xu, Danni Xu, Lu Cao, Huiqin Xue, Qingxiang Meng & Yun Niu

  4. Tianjin’s Clinical Research Center for Cancer, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, China

    Jing Liu, Cong Xu, Danni Xu, Lu Cao, Huiqin Xue, Qingxiang Meng & Yun Niu

  5. Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, China

    Jing Liu, Cong Xu, Danni Xu, Lu Cao, Huiqin Xue, Qingxiang Meng & Yun Niu

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  1. Jing Liu
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  2. Cong Xu
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Contributions

Yun Niu contributed to the design of the study and re-evaluate the cases; Jing Liu contributed significantly to the analysis of the results and wrote the manuscript; Danni Xu and Cong Xu performed the data analyses and provided writing assistance; Lu Cao, Huiqin Xue and Qingxiang Meng helped performed the analysis with constructive discussions. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yun Niu.

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The study protocol was approved by the Human Ethical Committee of Tianjin Medical University Cancer Institute and Hospital and has been performed in accordance with the Declaration of Helsinki (1964) and its later amendments.

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The authors declare that they have no conflict of interest.

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Informed consent was obtained from all patients before their surgery and before examination of the specimens.

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Liu, J., Xu, C., Xu, D. et al. The expression and prognostic role of EBP1 and relationship with AR in HER2+ breast cancer. Virchows Arch 477, 279–289 (2020). https://doi.org/10.1007/s00428-020-02773-0

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