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

VIRCHOWS ARCHIV(2020)

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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 (EBP1 high ) and 73 (52.1%) showed low/no expression of EBP1 (EBP1 low/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 EBP1 low/no group had poorer overall survival (OS) and disease-free survival (DFS) compared with other groups (AR − and EBP1 low/no , AR + and EBP1 high , and AR − and EBP1 high ). AR + and EBP1 low/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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Key words
HER2 positive breast cancer,ErbB3 binding protein 1,Androgen receptor,Prognosis,Targeted therapy
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