Docetaxel is a major drug in the treatment of metastatic breast cancer. In HER2 negative tumor, the first line treatment is based on docetaxel containing regimen: docetaxel alone, docetaxel + anthracycline or docetaxel + capecitabine. The efficacy of docetaxel in combination with trastuzumab has been demonstrated in first line metastatic breast cancer overexpressing erbB2 receptor. The response rate (RR) and the time to progression (TTP) observed were even higher than those obtained with paclitaxel +trastuzumab. Docetaxel is more and more used in first line metastatic setting, becoming the first Taxane used in this setting.As trastuzumab may raise safety/tolerability concerns, and as its interest in trastuzumab refractory patients may be limited, there is a need to find new drugs to combine with docetaxel in breast cancer, and to address the specific interaction/safety profile of this combination.The association of lapatinib and docetaxel will be the key combination in metastatic breast cancer development for GSK.The conclusion of a phase I trial EGF 10021 trial conducted in the US which assessed the combination of lapatinib and docetaxel showed that the acceptable optimal tolerated regimen (OTR) of docetaxel (75 mg/m²) was obtained in combination with lapatinib 1250 mg with systematic growth factor support.Data from an ongoing EGF100161 phase I study evaluating the OTR of lapatinib + docetaxel + trastuzumab shows that the association of lapatinib 1250 mg with docetaxel 75mg/m² is haematological toxic and has recently been amended to evaluate lapatinib 1250 mg with docetaxel 75 mg/m² with systematic growth factor support.A phase I/II EORTC study evaluating docetaxel plus lapatinib in neoadjuvant breast cancer patients has just started. The phase I part of this study will evaluate several lapatinib and docetaxel dose levels before conducting phase II.