c-erbB2 and topoisomerase II alpha protein expression independently predict poor survival in primary human breast cancer: a retrospective study

Introduction c-erbB2 ( also known as HER-2/neu) and topoisomerase II alpha are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIa protein influences the long-term outcome of patients with primary breast cancer. Methods In this study c-erbB2 and topoisomerase IIa protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. Results Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIa protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase II alpha overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIa was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIa showed the worst disease outcome ( P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIa or c-erbB2 overexpression. Conclusion The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIa in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer.