New developments and future directions in systemic therapy.

Adjuvant systemic therapies for breast cancer have led to a significant reduction in the risk of relapse and improvement in overall survival. However, a substantial proportion of breast cancer patients still ultimately experience relapse with metastatic disease. Here we review recent progress in trials of systemic therapies, including endocrine therapy, chemotherapy and targeted therapies for breast cancer. A current challenge for translational research is to identify drivers of resistance that may be amenable to therapy, as well as potential compensatory mechanisms that might limit the effectiveness of novel therapies. Unfortunately, not all targeted agents entering clinical trials will show sufficient efficacy to be approved for use. We highlight key findings from trials of novel agents, and the need for further research to identify biomarkers of response to systemic therapies in breast cancer.