Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action.
Due to their favourable tolerability profiles, endocrine therapies have long been considered the treatment of choice for hormone-sensitive metastatic breast cancer. However, the oestrogen agonist effects of the available selective oestrogen receptor modulators, such as tamoxifen, and the development of cross-resistance between endocrine therapies with similar modes of action have led to the need for new treatments that act through different mechanisms. Fulvestrant ('Faslodex') is the first of a new type of endocrine treatment--an oestrogen receptor (ER) antagonist that downregulates the ER and has no agonist effects. This article provides an overview of the current understanding of ER signalling and illustrates the unique mode of action of fulvestrant. Preclinical and clinical study data are presented in support of the novel mechanism of action of this new type of ER antagonist.
Osborne
C K
CK
Department of Medicine, Baylor College of Medicine, Houston, TX, USA. kosborne@bcm.tmc.edu
Wakeling
A
A
Nicholson
R I
RI
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D000077267:Fulvestrant; D004958:Estradiol