Trastuzumab has had an enormous impact on the clinical management of breast cancer: the survival of Her-2-positive metastatic breast cancer patients has improved significantly and tumor Her-2 status has been built into the decision-making tree for primary breast cancer patients. Several pioneering studies have shown that trastuzumab-combined chemotherapy elicits high levels of pathological complete response in the neoadjuvant setting. Currently, therefore, a more precise understanding of the mechanisms of therapeutic response is needed so that trastuzumab-based therapies can be optimized more individually. It might also be important to investigate, with greater depth, the interaction between the Her-axis and the hormone-axis. This short review describes and discusses these topics.