Especially for diseases that are not curable such as metastatic breast cancer (MBC), the maintenance of quality of life is one of the main aims of treatments. Adverse events are well-known side effects of any cytostatic treatment and impact the patients' quality of life. Therefore, new treatment options are developed that should stop or at least slow down metastatic spread of cancer without causing negative side effects in terms of high-grade adverse events. For patients with hormone-receptor positive and HER2 positive MBC the combination of HER2-targeted therapy with endocrine therapy has already been proven to be an effective and in many cases valuable alternative to the combination of HER2-targeted therapy with chemotherapy. The high relevance of HER2-neu-targeted/endocrine treatment combinations derives from the fact that potential chemotherapy-related toxicity can be avoided, which in turn positively affects quality of life.The combination of dual HER2-targeted therapy with trastuzumab and pertuzumab plus endocrine therapy might offer a better treatment option in patients with HER2 positive and hormone-receptor positive MBC. However, this combination has not been evaluated and compared to the combination of dual HER2-targeted plus chemotherapy in a prospective randomized phase III clinical trial.