| Background and Objectives:Triple-negative breast cancer is considered to be a special subgroup of breast cancer that has aggressive behaviors, high rate of visceral metastasis and poor outcome. Patients with triple-negative breast cancer do not benefit from endocrine therapy or trastuzumab therapy, and chemotherapy is currently the mainstay of systemic therapeutic strategy for them. It's worthy to study the mechanism of development and metastasis of triple-negative breast cancer, and the research would become theoretical basis of therapeutic strategy for patients with this disease. Recently, CXC chemokine receptor 4 (CXCR4) has been shown to play important roles in the development and metastasis of breast cancer cells, and blockage of CXCR4 signal pathway can inhibit the growth, proliferation and metastasis of cancer cells. High-expression of CXCR4 in cancer specimens can predict poor outcome for patients with breast cancer. In the present study, immunohistochemistry (IHC) was used to detect the expression level of CXCR4 in triple-negative breast cancer, Her-2 overexpression breast cancer and also luminal breast cancer. We aimed to find out the difference of CXCR4 expression level among breast cancer subgroups, analyze the correlation between CXCR4 expression level and clinicopathological features and clinical outcome in triple-negative breast cancer patients, investigate the roles of CXCR4 in the development and metastasis of triple-negative breast cancer and the prognostic value of CXCR4 for patients with this disease.Materials and Methods: 61 patients with triple-negative breast cancer were prospectively accrued and analyzed, while 52 patients with Her-2 overexpression breast cancer and 40 patients with luminal breast cancer were evaluated for comparison. CXCR4 expression levels were detected in 153 archival breast cancer samples by immunohistochemistry. All data were analyzed with SPSS 17.0 software. The comparison of CXCR4 expression levels among the three breast cancer subtypes, the correlation between CXCR4 expression level and clinicopathological characteristics were performed by chi-square test and Fisher's exact test. Disease-free survival (DFS) and Overall survival (OS) were reported in groups with high and low level of CXCR4 expression, by using the Kaplan–Meier survival analyses and log-rank test. Univariate and multivariate Cox analyses were applied to quantify the impact of CXCR4 expression on patient survival. Statistically significance was defined as P≤0.05.Results:①The rate of CXCR4 high-expression in triple-negative breast cancer, Her-2 overexpression breast cancer and luminal breast cancer was 75.4%, 48.1%, 35.0%, respectively, the difference was statistically significant. (χ~2 = 17.761, P<0.001).②In triple-negative cohort, CXCR4 expression level correlated with menstrual status, tumor size, tumor stage and histological grade (P<0.05). Moreover, node-positive tumors had higher rate of CXCR4 high-expression compared with node-negative tumors (P=0.085), patients with metastatic disease had higher rate of CXCR4 high-expression than those who remained disease free (P=0.115), but neither of them was statistically significant. However, CXCR4 expression level had no correlation with age or family history of cancer.③In triple-negative cohort, patients with CXCR4 high-expression tumors had significantly lower 2, 3, 5-year DFS rates compared with CXCR4 low-expression groups (χ~2=4.226,P=0.040), and patients with CXCR4 high-expression tumors had a 4.446-fold (95% CI=1.042-18.979; P=0.044) increase in relative risk of cancer recurrence compared with patients with CXCR4 low-expression tumors.④In triple-negative cohort, patients with CXCR4 high-expression tumors had significantly lower 2, 3, 5-year OS rates compared with CXCR4 low-expression groups (χ~2=4.012,P=0.045), while patients with CXCR4 high-expression tumors had a 3.803-fold (95% CI=0.892-16.204; P=0.071) increase in relative risk of cancer-relative death compared with patients with CXCR4 low-expression tumors.5 In Her-2 overexpression cohort and luminal cohort, there was no difference of DFS or OS between patients with CXCR4 high-expression tumors and patients with CXCR4 low-expression tumors. (P>0.05).Conclusion:①The expression of CXCR4 was detected in cytoplasm of breast cancer cells. Triple-negative breast cancer had higher rate of CXCR4 high-expression in the primary tumors compared with Her-2 overexpression breast cancer and luminal breast cancer.②In triple-negative cohort, CXCR4 expression level correlated with tumor size, tumor stage and histological grade. CXCR4 high-expression predicted poor outcome for patients with triple-negative breast cancer.③There was no correlation between CXCR4 expression level and DFS or OS of patients with Her-2 overexpression breast cancer or luminal breast cancer. |
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