High preoperative serum TIMP-1 is a prognostic indicator for survival in breast carcinoma

The amount of the immunoreactive protein for the tissue inhibitor of the matrix metalloproteinase-1 (TIMP-1) was studied prospectively from the pretreatment sera of 71 breast carcinoma patients using an enzyme-linked immunoassay (ELISA). The study consisted of patients with a primary breast carcinoma diagnosed between 1988 and 1991. The median follow-up time was more than 10 years, and routine adjuvant treatment was not used in the primary treatment. High TIMP-1 (> 196 ng/ml) was found to correlate with a poor relapse-free survival (RFS) in primary node-negative breast carcinoma. After 10 years of the follow-up only 42% of the patients with a high preoperative serum TIMP-1-level were free of the relapse, whereas 82% of the patients with a low serum TIMP-1 enjoyed a long RFS-time (log rank p =0.009). High serum TIMP-1 also indicated poor RFS (p = 0.02) and overall survival (p = 0.05) in stage I breast carcinoma. In Kaplan-Meier analysis the RFS was 89% in patients with a low serum level of TIMP-1 compared to 52% in patients with a high serum concentration of TIMP-1. In conclusion, preoperative high serum TIMP-1 levels predict poor outcome in primary breast carcinoma. In multivariate analysis preoperative high serum TIMP-1 increases the risk of relapse 3.4-fold during the first 10 years of follow-up in primary node-negative breast carcinoma.