Background: (Metastatic) breast cancer is a heterogeneous entity in which every disease subtype requires an individualized systemic treatment approach. Methods: We reviewed the currently available data regarding systemic therapy of breast cancer and present a review of historical and current treatment approaches, with the publications cited covering a time span from 1896 to the last ASCO 2015. Results: Systemic therapy of metastatic breast cancer may include chemotherapy, endocrine therapy, and targeted therapies (e.g. antibody-based approaches). Based on the patient's breast cancer subtype, these agents may be employed alone or in combination. Therefore, characterization of the phenotype of the disease is necessary and may include biopsy of the metastatic site. Novel therapeutic approaches include immunologic therapies as well as PARP, PI3K and CDK 4/6 inhibitors, which are currently under investigation in clinical trials. Conclusion: Systemic therapy of metastatic breast cancer requires complex and individualized treatment approaches that are best offered in an interdisciplinary setting.

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