Serial topoisomerase II expression in primary breast cancer and response to neoadjuvant anthracycline-based chemotherapy

Objective: We analyzed the value of topoisomerase IIalpha ( Topo II) in predicting the clinical response to anthracycline-based neoadjuvant chemotherapy in breast cancers and the potential changes in Topo II after chemotherapy. In parallel, HER2, which is commonly coexpressed with Topo II, and p53, a modulator of chemotherapy activity, were also analyzed. Methods: Forty-one patients with primary breast cancer and treated with neoadjuvant anthracycline-based chemotherapy (FAC or FEC) were included for the present study. Topo II, HER2 and p53 expression were measured by immunohistochemistry in pre and post chemotherapy ( at the time of surgery), tumor specimens and the results were correlated with the clinical response. Results: Topo II was overexpressed in 16 of 41 (31%) tumors before treatment, and this overexpression was significantly associated with clinical response ( p = 0.03). HER2 and p53 were unrelated to response. Notably, Topo II overexpression, but not HER2 or p53, was lost in specimens after chemotherapy ( p = 0.01). Conclusion: The observed link between Topo II and the clinical response to neoadjuvant anthracycline-based chemotherapy, together with its after chemotherapy, implies that Topo II deserves further testing in a prospective setting as a predictive marker. Copyright (C) 2004 S. Karger AG, Basel.