Microsomal Epoxide Hydrolase Expression as a Predictor of Tamoxifen Response in Primary Breast Cancer: A Retrospective Exploratory Study With Long-Term Follow-Up

Abstract

PURPOSE: It has been suggested that estrogen receptor–independent high-affinity binding sites for antiestrogens could limit their local bioavailability and response. Microsomal epoxide hydrolase (mEH) was recently shown to be a component of the antiestrogen binding site complex. We investigated whether mEH expression in primary breast tumors is related to disease outcome and to the efficacy of tamoxifen treatment. PATIENTS AND METHODS: Expression of mEH was semiquantitatively assessed by immunohistochemistry in sections prepared from archival paraffin blocks of primary breast cancers from 179 patients with a mean follow-up time of 81 months. RESULTS: Expression of mEH was correlated with poor disease outcome in all patients (P < .01; n = 179) and in patients receiving tamoxifen (P < .01; n = 78), but not in patients not treated with tamoxifen. Moreover, mEH was an independent prognostic factor by Cox regression analysis. CONCLUSION: The results of this first exploratory study suggest that mEH expression in primary breast cancer could be of predictive value for response to tamoxifen treatment and/or may be a novel independent prognostic factor for survival. The results are in agreement with the model that mEH participates in an estrogen receptor–independent tamoxifen- binding complex.