We previously reported that the combination of chemotherapy with the anti-HER2 antibody trastuzumab produced a synergistic cytotoxic interaction in HER2-negative breast cancer cells endogenously overexpressing the HER3/HER4 ligand heregulin-β1 (HRGβ1) (Menendez et al, 2006). This evidence concerns the gene ERBB4 and breast carcinoma.