Selective estrogen receptor modulators in clinical practice: a safety overview.
BACKGROUND
Selective estrogen receptor (ER) modulators (SERMs) are a class of nonsteroidal compounds that interact with ERs, each with a distinct tissue-specific profile. Depending upon the degree of ER agonism/antagonism at the target tissue, SERMs show efficacy for various indications including osteoporosis, dyspareunia, and breast cancer, and are associated with safety risks.


METHODS
This review describes the safety profile of SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, lasofoxifene, and ospemifene) and fulvestrant (a pure ER antagonist) from Phase III trials, long-term extension studies, and active comparator studies. Tamoxifen, a first-generation SERM, is indicated for breast cancer prevention and treatment but is associated with serious safety concerns including endometrial cancer, venous thromboembolic events (VTE), and stroke. Toremifene, raloxifene, bazedoxifene, lasofoxifene, and ospemifene present generally improved, though distinctly different, safety profiles compared with tamoxifen, especially with endometrial cancer and stroke. However, the risk of VTE remains a concern for most SERMs.


CONCLUSIONS
Each SERM presents a unique risk/benefit profile based on varying indications and tissue-specific ER agonist and antagonist effects, making careful patient selection and ongoing patient monitoring crucial aspects of treatment. Future research may focus on identifying new SERMs for endocrine-resistant and endocrine-responsive cancers and post-menopausal symptoms.
Pfizer Laboratories , IPC 004, Ramsgate Road, Sandwich, Kent, CT13 9NJ , UK +44 1304 646911 ; +44 1304 649103 ; amanda.ellis@pfizer.com.
Amanda J
AJ
Ellis
Vicky M
VM
Hendrick
Robert
R
Williams
Barry S
BS
Komm
D001943:Breast Neoplasms / Q000188:drug therapy; D016903:Drug Monitoring; D004414:Dyspareunia / Q000188:drug therapy; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D018579:Patient Selection; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*
D004965:Estrogen Antagonists; D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators
bazedoxifene; fulvestrant; lasofoxifene; ospemifene; raloxifene; safety; selective estrogen receptor modulator; tamoxifen; toremifene