New Approaches for Hormone-Receptor Positive Metastatic Breast Cancer

Overcoming endocrine resistance remains critical to further enhancing the benefit of existing endocrine therapies in estrogen receptor (ER) positive metastatic breast cancer. Preclinical research has significantly improved our understanding of molecular mechanisms associated with endocrine resistance. In turn, clinical research is focusing on designing trials that combine endocrine therapies with targeted inhibitors of specific signalling pathways that have been implicated in endocrine resistance. To date, first line studies have largely been disappointing, with many phase III trials failing to demonstrate a significant delay in endocrine resistance by the addition of a given targeted therapy. In contrast, the more successful trials have been performed in selected populations with acquired endocrine resistance. Numerous therapeutic agents are currently being tested in combination with endocrine therapies based on varying levels of preclinical data to support their use. In this review we provide the most recent advances in ER+ breast cancer, giving emphasis to recently concluded or ongoing trials with the potential to change current clinical practice.