Introduction: c-erbB2 (also known as HER-2/neu) and topoisomerase IIalpha are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIalpha protein influences the long-term outcome of patients with primary breast cancer.
Methods: In this study c-erbB2 and topoisomerase IIalpha 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 IIalpha protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIalpha overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIalpha was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIalpha showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIalpha or c-erbB2 overexpression.
Conclusion: The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIalpha in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer.