High preoperative plasma TIMP-1 is prognostic for early relapse in primary breast carcinoma

Abstract

TIMP-1 is a natural inhibitor of extracellular matrix degrading enzymes called matrix metalloproteinases. In addition to its capacity to inhibit matrix degradation, TIMP-1 has been shown to promote cell growth and inhibit apoptosis. The expression of TIMP-1 in tumor tissue, as well as in circulating blood, has therefore been shown to associate with worsened survival in several malignancies. In our study, a prospective series of 213 patients with primary breast carcinoma was assessed. Circulating pre- and postoperative TIMP-1 levels were assayed using enzyme-linked immunosorbent assay analysis. It was shown that high preoperative plasma TIMP-1 was a powerful predictor of systemic early relapse in breast carcinoma, with HR 8.1 (95% CI 1.8–37.6) (p = 0.007) as a log-transformed continuous variable in Cox regression univariate analysis. It was shown to be independent of, and superior to, nodal status as a prognostic variable in multivariate analysis, and not associated with any known prognostic clinicopathological parameters. Kaplan-Meier analysis showed that the patients belonging to the highest quartile of circulating TIMP-1 levels had a worsened recurrence-free survival of 79% compared to 94% RFS among patients in the lower quartiles (p = 0.016). The postoperative levels of circulating plasma TIMP-1 were not found to be prognostic for relapse. In conclusion, preoperative plasma TIMP-1 was found to be a powerful prognostic factor for early systemic relapse in primary breast carcinoma. © 2008 Wiley-Liss, Inc.