The second study run by our group was based on the same series of patients evaluated in the first study, but, this time, both HER-2 and topo II a genes were evaluated by fluorescence in-situ hybridization (FISH), which allows the detection of gene aberrations. The main findings of the second study were quite consistent with the pre-clinical data suggesting that only HER-2 amplified/topo II a amplified tumours show great sensitivity to anthracyclines while the efficacy of these same agents in HER-2 amplified/topo II a non-amplified tumors is comparable to the efficacy of other drugs or regimens like CMF.