ERBB2 and breast cancer: Despite many important findings that have been reported on the underlying mechanisms of resistance to trastuzumab [11] and lapatinib [10], a number of dilemmas remain [44, 45]: 1) It is unclear if resistance mechanisms for all erbB2-targeted therapies, such as trastuzumab and lapatinib, are similar; 2) There are no accurate methods to identify which breast cancer patients may benefit from, or be resistant to erbB2-targeted therapeutics selected; 3) We lack reliable biomarkers to predict the efficacy of trastuzumab and lapatinib against erbB2-positive breast cancer.