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

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.

KEYWORDS: Androgen receptor, ErbB3 binding protein 1, HER2 positive breast cancer, Prognosis, Targeted therapy