DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

The α isoform of Topoisomerase II α (Topo IIα) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo II α expression level and chemosensitivity of target cancer cells. To verify this effect in vivo , we selected 125 patients presenting with T 2 >3 cm and T 3 N 0–1 M 0 breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo II α . Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3–6.4, P =0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41–7.93, P =0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58–9.25, P =0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43–7.86, P =0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/ neu . Our clinical results confirm in vitro data on the relationship between Topo II α expression and tumour chemosensitivity and thus may have important practical implications.