Pure oestrogen antagonists for the treatment of advanced breast cancer.
AffiliationCRUK Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK. firstname.lastname@example.org
MetadataShow full item record
AbstractFor more than 30 years, tamoxifen has been the drug of choice in treating patients with oestrogen receptor (ER)-positive breast tumours. However, research has endeavoured to develop agents that match and improve the clinical efficacy of tamoxifen, but lack its partial agonist effects. The first 'pure' oestrogen antagonist was developed in 1987; from this, an even more potent derivative was developed for clinical use, known as fulvestrant (ICI 182,780, 'Faslodex'). Mechanistic studies have shown that fulvestrant possesses high ER-binding affinity and has multiple effects on ER signalling: it blocks dimerisation and nuclear localisation of the ER, reduces cellular levels of ER and blocks ER-mediated gene transcription. Unlike anti-oestrogens chemically related to tamoxifen, fulvestrant also helps circumvent resistance to tamoxifen. There are extensive data to support the lack of partial agonist effects of fulvestrant and, importantly, its lack of cross-resistance with tamoxifen. In phase III studies in patients with locally advanced or metastatic breast cancer, fulvestrant was at least as effective as anastrozole in patients with tamoxifen-resistant tumours, was effective in the first-line setting and was also well tolerated. These data are supported by experience from the compassionate use of fulvestrant in more heavily pretreated patients. Further studies are now underway to determine the best strategy for sequencing oestrogen endocrine therapies and to optimise dosing regimens offulvestrant. At present, and for the foreseeable future, fulvestrant is the only oestrogen antagonist with no agonistic effects licensed for the treatment of advanced breast cancer in postmenopausal women. Other similar oestrogen antagonists are undergoing research and development, with a few currently being evaluated in phase II trials.
CitationPure oestrogen antagonists for the treatment of advanced breast cancer. 2006, 13 (3):689-706 Endocr. Relat. Cancer
- The use of selective estrogen receptor modulators and selective estrogen receptor down-regulators in breast cancer.
- Authors: Howell SJ, Johnston SR, Howell A
- Issue date: 2004 Mar
- Selective oestrogen receptor modulators/new antioestrogens: a clinical perspective.
- Authors: Robertson JF
- Issue date: 2004 Dec
- Preliminary experience with pure antiestrogens.
- Authors: Howell A
- Issue date: 2001 Dec
- Anti-oestrogens but not oestrogen deprivation promote cellular invasion in intercellular adhesion-deficient breast cancer cells.
- Authors: Borley AC, Hiscox S, Gee J, Smith C, Shaw V, Barrett-Lee P, Nicholson RI
- Issue date: 2008
- Preclinical and clinical experience with fulvestrant (Faslodex) in postmenopausal women with hormone receptor-positive advanced breast cancer.
- Authors: Bundred N
- Issue date: 2005