Pharmacological insights on novel oral selective estrogen receptor degraders in breast cancer

Abstract

The therapeutic landscape of estrogen receptor (ER)-positive breast cancer includes endocrine treatments with aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), and selective estrogen receptor degraders (SERDs). Fulvestrant is the first approved SERD with proven efficacy and good tolerability in clinical practice. However, drug resistance, low receptor affinity, and parental administration stimulated the search for new oral SERDs opening a new therapeutic era in ER + breast cancer. Elacestrant is an orally bioavailable SERD that has been recently approved by the FDA for postmenopausal women with ER+, human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Other molecules of the same class currently tested in clinical trials are amcenestrant, giredestrant, camizestrant, and imlunestrant. The current review article offers a detailed pharmacological perspective of this emerging drug class, which may help with their possible future clinical applications.

Keywords: Breast cancer; Drug-drug interactions; Pharmacodynamics; Pharmacokinetics; SERDs.