The use of the antibody trastuzumab to inhibit human epidermal growth factor receptor 2 (erbB2), which is present on specific types of breast cancer, is a paradigm shift in cancer therapy, as it provides a more specific and less toxic approach to treat breast cancer compared to chemotherapy. However, many patients with erbB2 positive breast cancer show no response to trastuzumab or they acquire resistance to trastuzamab treatment with one year. Recently, it has been shown that increased expression of two other surface receptors, human epidermal growth factor receptor 3 (erbB3) and insulin-like growth factor receptor (IGF-1R), is associated with the development of trastuzamab resistance. ErbB3 and IGF-1R form a complex with erbB2, which blocks trastuzamab activity and allows breast cancer cells to survive and proliferate. We propose to develop new antibodies that target erbB3 and IGF- 1R as a promising strategy to treat erbB2-positive trastuzumab sensitive and resistant breast cancer.