Pure oestrogen antagonists for the treatment of advanced breast cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72647
Title:
Pure oestrogen antagonists for the treatment of advanced breast cancer.
Authors:
Howell, Anthony ( 0000-0002-3879-5991 )
Abstract:
For 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.
Affiliation:
CRUK Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK. maria.parker@christie-tr.nwest.nhs.uk
Citation:
Pure oestrogen antagonists for the treatment of advanced breast cancer. 2006, 13 (3):689-706 Endocr. Relat. Cancer
Journal:
Endocrine-Related Cancer
Issue Date:
Sep-2006
URI:
http://hdl.handle.net/10541/72647
DOI:
10.1677/erc.1.00846
PubMed ID:
16954425
Type:
Article
Language:
en
ISSN:
1351-0088
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHowell, Anthony-
dc.date.accessioned2009-07-06T16:41:04Z-
dc.date.available2009-07-06T16:41:04Z-
dc.date.issued2006-09-
dc.identifier.citationPure oestrogen antagonists for the treatment of advanced breast cancer. 2006, 13 (3):689-706 Endocr. Relat. Canceren
dc.identifier.issn1351-0088-
dc.identifier.pmid16954425-
dc.identifier.doi10.1677/erc.1.00846-
dc.identifier.urihttp://hdl.handle.net/10541/72647-
dc.description.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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectCancer Stagingen
dc.subjectOestrogen Antagonistsen
dc.subjectOestrogen Receptorsen
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBreast Neoplasms-
dc.subject.meshEstradiol-
dc.subject.meshEstrogen Antagonists-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshNeoplasm Staging-
dc.subject.meshReceptors, Estrogen-
dc.subject.meshSignal Transduction-
dc.titlePure oestrogen antagonists for the treatment of advanced breast cancer.en
dc.typeArticleen
dc.contributor.departmentCRUK Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK. maria.parker@christie-tr.nwest.nhs.uken
dc.identifier.journalEndocrine-Related Canceren
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