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dc.contributor.authorJohnston, SR
dc.contributor.authorMartin, L-A
dc.contributor.authorDowsett, M
dc.date.accessioned2018-07-11T13:49:33Z
dc.date.issued2005-01
dc.identifier.citationBreast cancer research and treatment, 2005, 93 Suppl 1 pp. S19 - S25
dc.identifier.issn0167-6806
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2039
dc.identifier.eissn1573-7217
dc.identifier.doi10.1007/s10549-005-9038-2
dc.description.abstractThe third-generation non-steroidal aromatase inhibitors (AIs) are challenging tamoxifen as treatments of choice for early and advanced breast cancer in postmenopausal women with estrogen receptor (ER)-positive disease. However, patients who initially respond to AIs eventually develop resistance to treatment and experience disease progression. To establish the optimal endocrine therapy following AI resistance, it is essential to understand the mechanisms that contribute to the loss of response. Data from in vitro models have suggested that acquired AI resistance is due to enhanced sensitization to low estrogen levels during long-term estrogen deprivation (LTED). Cross-talk between the ER and various growth-factor-receptor signaling pathways, including human epidermal growth factor receptor 2, and the insulin-like growth factor pathway, may also be implicated. Therefore, endocrine therapies that abolish estrogen signaling via removal of the ER could be effective in patients with AI-resistant disease. Fulvestrant ('Faslodex') is a new ER antagonist with no agonist effects that binds, blocks and degrades the ER. Due to its unique mode of action and lack of cross-resistance with existing treatments, fulvestrant is an effective therapeutic agent for use in sequential endocrine regimens. Fulvestrant has established efficacy in tamoxifen-resistant disease and there is a growing body of evidence demonstrating its efficacy in patients with AI-resistant disease. In preclinical models, MCF-7 cells undergoing LTED are refractory to tamoxifen but sensitive to fulvestrant, suggesting fulvestrant is a more appropriate choice following AI resistance. The steroidal AI, exemestane is also an option in non-steroidal AI-resistant disease. Clinical trials are underway to compare fulvestrant with exemestane as an appropriate therapy following the onset of AI resistance.
dc.formatPrint
dc.format.extentS19 - S25
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectNitriles
dc.subjectTriazoles
dc.subjectAndrostadienes
dc.subjectEstradiol
dc.subjectEstrogen Receptor Modulators
dc.subjectAntineoplastic Agents, Hormonal
dc.subjectAromatase Inhibitors
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectClinical Trials as Topic
dc.subjectFulvestrant
dc.subjectAnastrozole
dc.titleLife following aromatase inhibitors--where now for endocrine sequencing?
dc.typeJournal Article
rioxxterms.versionofrecord10.1007/s10549-005-9038-2
rioxxterms.licenseref.startdate2005-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBreast cancer research and treatment
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume93 Suppl 1
pubs.embargo.termsNot known
icr.researchteamEndocrine Therapy Resistanceen_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorJohnston, Stephenen
dc.contributor.icrauthorMartin, Lesley-Annen
dc.contributor.icrauthorDowsett, Mitchen


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