Oral Selective Estrogen Receptor Degraders (SERDs) in Breast Cancer: Advances, Challenges, and Current Status

Several endocrine therapies are currently available for the treatment of estrogen receptor (ER) positive breast cancer, but the clinical benefit of these agents is limited by endocrine therapy drug resistance. A common mechanism of endocrine therapy resistance is ESR1 mutations. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has activity against ESR1 mutant tumors but requires intramuscular injection and has poor bioavailability that precludes optimal drug dosing. This led to the development of second-generation SERDs which are potent and have improved oral bioavailability and pharmacokinetics. Several of these oral SERDs are now in phase III trials in both the early and advanced ER positive breast cancer settings. This review summarizes the background of oral SERD development, the current status and future perspectives.

Automated summary

The translated article discusses the limitations of current endocrine therapies for ER-positive breast cancer and the mechanisms of drug resistance, focusing on ESR1 mutations. It also provides an overview of the development and research progress of oral SERDs in improving treatment outcomes.