Abstract
PURPOSE: Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4). METHODS: We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared. RESULTS: In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p = 0.006). CONCLUSIONS: TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.