Selective Estrogen Receptor Degraders (SERDs)

Update on the most recent clinical evidence on selective estrogen receptor degraders (SERDs) in the treatment of hormone receptor (HR)-positive (HR +), human epidermal growth factor receptor 2 (HER2)-negative (HER2-) breast cancer.

Despite effective endocrine therapies, resistance commonly develops during treatment of HR + breast cancer and mutations in ESR1 account for a large proportion of resistance mechanisms. After demonstration of the superior efficacy of fulvestrant in ESR1-mutated tumors, recent advances allowed the development of a novel class of orally bioavailable selective estrogen receptor degraders (SERDs), which are beginning to revolutionize the field. The first approved oral SERD, elacestrant, is currently used in the second-line treatment of HR + /HER2- metastatic breast cancer, and a number of other oral SERDs are undergoing clinical evaluation in both the metastatic and early-stage settings.

SERDs are a rapidly developing class of antiestrogens that show activity in treatment of tumors harboring ESR1 mutations associated with resistance to earlier generations of endocrine therapy, but knowledge gaps remain, and further research is necessary to better define their optimal use.