Novel Endocrine Therapies: Current Status and Future Directions.

Recent advances in endocrine therapy have led to the development of novel oral agents that target estrogen receptor signaling in estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer. This review outlines key findings from clinical trials of Food and Drug Administration (FDA)-approved selective estrogen receptor degraders (SERDS), including elacestrant and imlunestrant, the newly FDA-approved proteolysis-targeting chimera (PROTAC) vepdegestrant, as well as emerging oral SERDs, PROTACs, complete estrogen receptor antagonists, selective estrogen receptor covalent antagonists (SERCAs), and other targeted therapies. We explore their mechanisms, efficacy, tolerability, and potential to improve treatment options and outcomes in both metastatic and early-stage disease.