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

Teesha Downton; Fiona Zhou; Davendra Segara; Rinath Jeselsohn; Elgene Lim

doi:10.2147/DDDT.S380925

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

Drug Des Devel Ther. 2022 Sep 2:16:2933-2948. doi: 10.2147/DDDT.S380925. eCollection 2022.

Authors

Teesha Downton^{1

2}, Fiona Zhou^{1

2}, Davendra Segara¹, Rinath Jeselsohn^#³, Elgene Lim^#^{1

2}

Affiliations

¹ Garvan Institute of Medical Research, Sydney, NSW, Australia.
² School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
³ Dana-Farber Cancer Institute, Boston, MA, USA.

^# Contributed equally.

Abstract

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.

Keywords: breast cancer; estrogen receptor; selective estrogen receptor degraders.

Publication types

Review

MeSH terms

Breast
Breast Neoplasms* / pathology
Estrogen Receptor alpha / genetics
Female
Humans
Mouth Neoplasms*
Receptors, Estrogen
Selective Estrogen Receptor Modulators / pharmacology
Selective Estrogen Receptor Modulators / therapeutic use

Substances

Estrogen Receptor alpha
Receptors, Estrogen
Selective Estrogen Receptor Modulators

Grants and funding

EL is supported by the National Breast Cancer Foundation Endowed Chair (EC17-02) and Love Your Sister foundation. RJ receives funding from the National Institute of Health/ National Cancer Institute (R01CA237414-01) and the Claudia Adams Barr Program.