Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2004 Mar;90 Suppl 1(Suppl 1):S2-6.
doi: 10.1038/sj.bjc.6601629.

Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action

C K Osborne  1 , A Wakeling, R I Nicholson
Affiliations
Review

Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action

C K Osborne et al. Br J Cancer. 2004 Mar.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Cellular distribution and activity of the ER. The known mechanisms of fulvestrant intervention in ER signalling are indicated with an asterisk. EGFR=epidermal growth factor receptor; ERE=oestrogen response element; ER=oestrogen receptor.
Figure 2
Figure 2
Structure of 17β-oestradiol, fulvestrant, tamoxifen and raloxifene.
Figure 3
Figure 3
Mechanism of action of fulvestrant at the level of transcriptional regulation. ERE=oestrogen response element; ER=oestrogen receptor; F=fulvestrant.
Figure 4
Figure 4
Mean (A) ER and (B) PgR levels after a single i.m. injection of 50, 125, or 250 mg fulvestrant, 20 mg tamoxifen, or placebo. Reproduced with the permission of Cancer Research (Robertson et al, 2001).
See this image and copyright information in PMC

References

    1. Addo S, Yates RA, Laight A (2002) A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers. Br J Cancer 87: 1354–1359 - PMC - PubMed
    1. Arun B, Anthony M, Dunn B (2002) The search for the ideal SERM. Expert Opin Pharmacother 3: 681–691 - PubMed
    1. ATAC Trialists' Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359: 2131–2139 - PubMed
    1. Beato M (1989) Gene regulation by steroid hormones. Cell 56: 335–344 - PubMed
    1. Bundred NJ, Anderson E, Nicholson RI, Dowsett M, Dixon M, Robertson JF (2002) Fulvestrant, an estrogen receptor downregulator, reduces cell turnover index more effectively than tamoxifen. Anticancer Res 22: 2317–2319 - PubMed