The association between the preoperative serum levels of lipocalin-2 and matrix metalloproteinase-9 (MMP-9) and prognosis of breast cancer

Background: Although a number of experimental studies have suggested the role of lipocalin-2 (LCN2) and matrix metalloproteinase-9 (MMP-9) in breast cancer progression, limited numbers of epidemiological studies have examined the relationship between the levels of lipocalin-2 and MMP-9 and breast cancer survival. Methods: Preoperative serum levels of lipocalin-2 and MMP-9 were measured in 303 breast cancer patients and 74 healthy controls recruited between 2004 and 2007. We examined the association between lipocalin-2 and MMP-9 levels and disease-free survival (DFS) using Cox proportional hazard regression model. Results: The serum levels of lipocalin-2 and MMP-9 were not significantly different between patients and controls (P > 0.05). Elevated lipocalin-2 and MMP-9 levels were associated with reduced DFS of breast cancer (P-trend = 0.029 and P-trend = 0.063, respectively). When lipocalin-2 and MMP-9 levels were categorized based on the combined risk score, patients with higher levels of both lipocalin-2 and MMP-9 exhibited poor DFS compared to patients with lower levels (P-trend = 0.004). Furthermore, these effects were profound in patients with BMI less than 25 kg/m(2) (adjusted hazard ratio (aHR), 3.17; 95% confidence intervals (CI), 1.66-6.06, P-trend < 0.001) or lymph-node negative breast cancer (aHR, 5.36; 95% CI, 2.18-13.2, P-trend < 0.001). Conclusions: Our study suggests that the elevated levels of lipocalin-2 and MMP-9 are associated with reduced breast cancer survival, particularly in patients with lower BMI and lymph-node negative breast cancers.