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Life sciences · Journal article
Expert Opinion on Drug Metabolism & Toxicology · October 23, 2026
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Introduction Oral selective estrogen receptor degraders (SERDs) have transformed the treatment landscape for patients with hormone receptor-positive, HER2-negative metastatic breast cancer harboring ESR1 mutations. As their use expands, understanding their pharmacokinetic properties, safety profiles, and drug–drug interaction (DDI) potential is essential, particularly in patients with hepatic impairment, comorbidities, and polypharmacy.Areas covered This review summarizes current evidence on the pharmacokinetics, metabolism, safety, dose modification strategies, and clinically relevant DDIs of the two FDA-approved oral SERDs, elacestrant and imlunestrant. Practical considerations regarding CYP3A4-mediated interactions, transporter-related DDIs, hepatic and renal impairment, and concomitant medication management are discussed.Expert opinion Oral SERDs demonstrate favorable safety profiles and substantially lower DDI burdens than CDK4/6 inhibitors, facilitating their integration into routine clinical practice. Elacestrant is more susceptible to CYP3A4-mediated interactions, whereas imlunestrant exhibits a lower interaction burden owing to its multiple metabolic pathways. Careful assessment of concomitant medications and hepatic function remains essential to optimize treatment efficacy and minimize toxicity. As clinical experience grows, a deeper understanding of the pharmacological characteristics of oral SERDs will further support individualized endocrine therapy for metastatic breast cancer.