Molecularly targeted therapy and immunotherapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer

The advent of targeted therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2(-) aBC) provides a novel therapeutic approach other than endocrine therapy. One targeted signaling pathway and three immune-checkpoints have been demonstrated to be in association with tumor proliferation and growth in HR+/HER2(-) aBC. A number of phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathway inhibitors demonstrate clinical activity against this tumor subtype. The CDK4/6 inhibitors as a single agent or in combination with endocrine therapy have produced promising tumor response with acceptable toxicity in patients with HR+/HER2(-) aBC. Programmed death 1/programmed death ligand 1 (PD1/PD-L1) and cytotoxic T lymphocyte antigen-4 inhibitors can also produce an antitumor immune response, which provides a proof-of-principle for the initial utilization of immunotherapy in breast cancer. The aim of the present review was to discuss the mechanisms of action, clinical efficacy and safety profiles of all the targeted biological therapies and immunotherapies that have been approved or are currently under evaluation for HR+/HER2(-) aBC.