Matrix metalloproteinases (MMPs) have been reported to be associated with invasive and metastatic behaviors of human malignant tumors. However, there is still limited knowledge about the role of matrix metalloproteinases-2 (MMP-2) in breast cancer. This study was designed with the aim to elucidate the possible relationship between the preoperative circulating MMP-2 and breast cancer. Fifty-seven consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation, and stored at -70 degrees C until assayed. The control group consisted of 12 patients with benign breast tumor (six with fibrocystic disease and six with fibroadenoma). Serum concentrations of MMP-2 were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor stage, age, estrogen receptor, lymph node status, and TNM staging were reviewed and recorded. The mean value of serum MMP-2 in patients with invasive breast cancer was 694.3+/-140.5 ng/ml and those of control group were 593.3+/-134.0 ng/ml and the difference was significant (P=0.026). Furthermore, there were significantly higher serum levels of MMP-2 in the patients with more advanced primary tumor staging (P=0.005), in the patients with more advanced lymph node status(P=0.011) and in the patients with more advanced TNM staging (P<0.001). In multivariate analysis, TNM staging (P<0.001) appeared as independent factor regarding the significant higher serum levels of MMP-2. Patients with more advanced TNM staging were shown to have higher serum MMP-2 levels. Thus preoperative serum MMP-2 levels might reflect the severity of invasive breast cancer and deserve further evaluation.