Abstract 1753: High expression of the microtubule destabilizing protein stathmin is prognostic for worse outcome in breast cancer

Abstract

Abstract INTRODUCTION: Taxanes are microtubule targeting agents (MTAs) and potent cytotoxic molecules recognized as highly effective chemotherapeutic agents. In large randomized clinical trials, taxane-based chemotherapies provided benefits in overall and disease-free survival, but they are accompanied by significant adverse effects. Thus the clinical utility of taxane therapy would be enhanced if there were companion diagnostic tests so that only the taxane-sensitive patients (about half of breast cancers) could be treated with this drug. Accumulating evidence indicates that microtubule associated proteins (MAPs) may be responsible for tumor cell resistance to taxanes. Here we use a large retrospective cohort to measure expression levels of stathmin, a microtubule destabilizing protein, and to determine prognostic value, as a first step toward development of a companion diagnostic. METHODS: Stathmin expression was measured in a large retrospective breast cancer cohort (n= 645) with 20 year follow-up using tissue microarray technology (TMA) in two-fold redundancy and quantitative immunofluorescence (AQUA). Patient stathmin expression levels were correlated with clinical, pathological, and disease free survival variables. RESULTS: Stathmin expression exhibited nonparametric distribution with high correlation (R= 0.70) between redundant TMA cores. Prognostic evaluation of the cohort using univariate analysis indicated an inverse correlation between high stathmin expression and overall survival (HR = 1.30, 95% confidence interval [CI] = 1.02-1.65; p< 0.028). Kaplan Meier survival analysis showed 10-year survival of 54% for patients with high stathmin expression versus a 65% survival rate for low expressers (log rank, P<.0058). Multivariate analysis indicated that high stathmin expression, nodal status, HER2 expression, and tumor size are independent predictors of survival. CONCLUSIONS: Stathmin expression in breast tumor tissue functions as a prognostic factor where high expression is associated with worse outcome. Since stathmin expression is useful in predicting survival, it may serve as marker to accurately select patients for current taxane-based or other anti-microtubule therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1753.