Role of Epstein-Barr Virus in Breast Cancer: Correlation with Clinical Outcome and Survival Analysis

Yi-Chiung Hsu; Ming-Han Tsai; Guani Wu; Chien-Liang Liu; Yuan-Ching Chang; Hung-Bun Lam; Pei-Yu Su; Chun-Fan Lung; Po-Sheng Yang

doi:10.7150/jca.93631

Role of Epstein-Barr Virus in Breast Cancer: Correlation with Clinical Outcome and Survival Analysis

J Cancer. 2024 Mar 4;15(8):2403-2411. doi: 10.7150/jca.93631. eCollection 2024.

Authors

Yi-Chiung Hsu^{1

2}, Ming-Han Tsai³, Guani Wu⁴, Chien-Liang Liu⁵, Yuan-Ching Chang⁵, Hung-Bun Lam⁵, Pei-Yu Su³, Chun-Fan Lung¹, Po-Sheng Yang^{5

6}

Affiliations

¹ Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan.
² Center for Astronautical Physics and Engineering, National Central University, Taoyuan, Taiwan.
³ Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
⁴ Department of Statistics & Data Science, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Department of General Surgery, MacKay Memorial Hospital, Taipei, Taiwan.
⁶ Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.

Abstract

Background: Breast cancer is the most prevalent cancer among women worldwide. The potential involvement of Epstein-Barr virus (EBV) in breast cancer pathogenesis has been a subject of debate, but its correlation with clinical outcomes remains uncertain. Methods: In this study, we collected 276 pathologically confirmed breast cancer tissue samples from the tissue bank of MacKay Memorial Hospital and the National Health Research Institutes in Taiwan. DNA was extracted from frozen tissue using The QIAamp DNA Mini Kit. The Taqman quantitative PCR method was employed to assess the EBV copy number per cell in these samples, using NAMALWA cells as a reference. We performed statistical analyses, including 2 × 2 contingency tables, Cox regression analysis, and Kaplan-Meier survival curves, to explore the association between clinicopathologic factors and survival outcomes in breast cancer patients. We analyzed both relapse survival, which reflects the period patients remain free from cancer recurrence post-treatment, and overall survival, which encompasses all-cause mortality. Results: Our results revealed a significant association between EBV status and relapse survival (hazard ratio: 2.75, 95% CI: 1.30, 5.86; p = 0.008) in breast cancer patients. However, no significant association was found in overall survival outcomes. Additionally, we observed significant associations between ER status and tumor histologic grade with both overall and relapse survival. Patients with EBV-positive tumors exhibited higher recurrence rates compared to those with EBV-negative tumors. Furthermore, we noted significant correlations between EBV status and HER-2 (p = 0.0005) and histological grade (p = 0.02) in our cohort of breast cancer patients. Conclusions: The presence of EBV in breast cancer tumors appears to exert an impact on patient outcomes, particularly concerning recurrence rates. Our findings highlight the significance of considering EBV status as a potential prognostic marker in breast cancer patients. Nonetheless, further research is essential to elucidate the underlying molecular mechanisms and develop novel therapeutic approaches.

Keywords: Epstein-Barr virus; Taqman qPCR; breast cancer; recurrence; survival.