Topoisomerase II alpha as a marker predicting anthracyclines' activity in early breast cancer patients: Ready for the primetime?

Purpose: This manuscript reviews and discusses results from randomised clinical studies evaluating topoisomerase II alpha (topo II) as a marker predicting anthracyclines' activity in early breast cancer patients. Methods: A Medline search has led to the identification of six phase III clinical trials, in which topo II has been retrospectively evaluated as a marker predicting anthracyclines' activity in the adjuvant setting. Results: Rates of topo II gene aberrations, in particular gene deletion, seem to vary substantially between the studies. No extensive correlation has been found between topo II gene status and protein levels. Five of the six trials suggest that topo II gene amplification is associated with increased tumour sensitivity to anthracyclines. Two of the three studies evaluating topo II gene deletions suggest that topo II deleted tumours might also derive an increased benefit from anthracyclines. Conclusion: Current data suggest that topo II might become a predictive tool to identify patients candidate to receive anthracyclines in the adjuvant setting. ongoing studies will likely address some pending issues which, at present, prevent the use of this marker in daily practice. (C) 2008 Elsevier Ltd. All rights reserved.