The role of topoisomerase IIalpha and HER-2 in predicting sensitivity to anthracyclines in breast cancer patients.

Human epidermal growth factor receptor-2 (HER-2) and topoisomerase IIalpha (topo IIalpha) co-inhabit chromosome 17. In the search for predictive biomarkers to refine clinical prescription of cytotoxic agents, both HER-2 and topo IIalpha are under exploration for their potential role in identifying individuals with early breast cancer who may benefit from anthracycline therapy. Whilst recent meta-analyses support a predictive role for HER-2 amplification, it remains unclear whether HER-2 is the critical biomarker or whether it is a surrogate marker for topo IIalpha alteration, a known drug target of anthracyclines. The major limitation in considering HER-2 as a single marker is heterogeneity within the subgroups of HER-2 positive and HER-2 negative disease. For topo IIalpha, current data is inconclusive. Issues plaguing this field are technical variability in marker definition, complex regulation pathway of topo IIalpha and lack of prospective, adequately powered studies. With current evidence, neither HER-2 nor topo IIalpha gene status can be considered clinically valuable markers for anthracycline benefit. This paper will focus on issues relating to reliable detection and predictive analyses of HER-2 and topo IIalpha, and highlight potential developments in improving individualized approach to anthracycline use in early breast cancer patients.