Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: a systematic review and meta-analysis.

BACKGROUND Breast cancer (BC) is a leading cause of cancer-related death in females worldwide. Previous studies have demonstrated that matrix metalloproteinases (MMPs) play key roles in metastasis and are associated with survival in various cancers. The prognostic values of MMP2 and MMP9 expression in BC have been investigated, but the results remain controversial. Thus, we performed the present meta-analysis to investigate the associations between MMP2/9 expressions in tumor cells with clinicopathologic features and survival outcome in BC patients. METHODS Eligible studies were searched in PubMed, Web of Science, EMBASE, CNKI and Wanfang databases. The associations of MMP2/9 overexpression in tumor cells with overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) were assessed by hazard ratio (HR) and 95% confidence interval (CI). The associations of MMP2/9 overexpression with clinicopathological features were investigated by calculating odds ratio (OR) and 95% CI. Subgroup analysis, sensitivity analysis, meta-regression, and analysis for publication bias were performed. RESULTS A total of 41 studies comprising 6517 patients with primary BC were finally included. MMP2 overexpression was associated with an unfavorable OS (HR = 1.60, 95% CI 1.33 -1.94, P < 0.001) while MMP9 overexpression predicted a shorter OS (HR = 1.52, 95% CI 1.30 -1.77, P < 0.001). MMP2 overexpression conferred a higher risk to distant metastasis (OR = 2.69, 95% CI 1.35-5.39, P = 0.005) and MMP9 overexpression correlated with lymph node metastasis (OR = 2.90, 95% CI 1.86 - 4.53, P < 0.001). Moreover, MMP2 and MMP9 overexpression were both associated with higher clinical stage and histological grade in BC patients. MMP9 overexpression was more frequent in patients with larger tumor sizes. CONCLUSIONS Tumoral MMP2 and MMP9 are promising markers for predicting the prognosis in patients with BC.