P4-09-26: Prognostic Significance of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) in Breast Cancer.

Abstract Background: Despite advances of systemic treatment in breast cancer guided by hormonal status and HER2 amplification, new prognostic and predictive factors are still warranted to optimize treatments among these patients. Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), a physiologic inhibitor of Matrix Metalloproteinases (MMPs), can act in both pro- and anti-tumoral effects. The prognostic significance of TIMP-1 in breast cancer is still controversial. This study aims to determine the prognostic significance of TIMP-1 in breast cancer. Material and Methods: One-hundred and seventy-six primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1. Immunohistochemical analysis was independently reviewed by two pathologists. Results: At the optimized cut-off point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.6 (p = 0.039), but without significant differences in overall survival (HR 1.29, p = 0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.2, p = 0.35), high expression was associated with shorter overall survival (HR 1.73, p = 0.027). In multivariate analysis, when considering stage, histologic grade, hormonal and HER2 status, TIMP-1 RNA levels remained independently prognostic for early relapse (HR 1.68, p = 0.04). Discussion: Elevated TIMP-1 RNA levels are independently prognostic for early recurrence, whereas protein overexpression of TIMP-1 is correlated with short overall survival in primary breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-26.