Developing themes in targeted therapies for hormone receptor–positive breast cancer

Abstract Breast cancer is the most common malignancy in women, with the majority classified as hormone receptor–positive (HR+) and HER2 receptor–negative (HER2−). After the approval of the CDK4/6 inhibitors, palbociclib, ribociclib and abemaciclib for advanced HR+/HER2− breast cancer, combinations of endocrine therapy (ET) and CDK4/6 inhibitors are becoming routine practice. However, drug resistance remains an important issue. To overcome this, multiple targeted therapies are in development, and several approaches are in clinical trial in combination with ET, including drugs that inhibit CDK7, FGFR, AURKA, HDAC and the PI3K–AKT–mTOR pathway. Triple combinations of investigational drugs with ET and CDK4/6 inhibitors are also being trialled.