Selective estrogen receptor modulators in clinical practice: a safety overview

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• bazedoxifene
• fulvestrant
• lasofoxifene
• ospemifene
• raloxifene
• safety
• selective estrogen receptor modulator
• tamoxifen
• toremifene

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Erratum

Acknowledgements

Medical writing support was provided by Karen Dougherty, PhD and Lauren Cerruto, at Peloton Advantage, LLC, and was funded by Pfizer.

Declaration of interest

This manuscript was funded by Pfizer Inc. A Ellis and V Hendrick are employees of Pfizer Laboratories, Sandwich, Kent, UK and R Williams and B Komm are employees of Pfizer Inc. USA. Medical writing support, funded by Pfizer, was received from Karen Dougherty and Lauren Cerruto of Peloton Advantage LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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