Vascular effects of aromatase inhibitors: data from clinical trials.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76575
Title:
Vascular effects of aromatase inhibitors: data from clinical trials.
Authors:
Howell, Anthony ( 0000-0002-3879-5991 ) ; Cuzick, Jack
Abstract:
Aromatase inhibitors (AIs) are becoming the endocrine treatment of first choice for postmenopausal women with hormone receptor-positive breast cancer and are under investigation for use in breast cancer prevention. AIs reduce circulating estrogen to barely detectable concentrations. It is possible that such a low concentration will be deleterious to the vascular system since estrogen receptors are known to be in the cell walls of blood vessels and estrogen is thought to be important in maintaining blood vessel integrity. Because most women who present with primary breast cancer are cured by surgery and systemic therapy and the major cause of female death is vascular disease, it is particularly important to investigate the vascular side effects of AIs in current breast cancer adjuvant and prevention trials. In order to set the vascular toxicities of AIs reported in the current adjuvant trials into context, here we compare them with the toxicities seen during treatment with hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs). Clinical trial evidence indicates that HRT increases risk of coronary heart disease (CHD) whereas SERMs and AIs (to date) appear to be neutral. Cerebrovascular disease and venous thromboembotic events are increased by HRT and SERMs but appear to be unaffected by treatment with AIs. Cognitive function is also considered here since it may also have a vascular component and is potentially a serious potential side effect/benefit of AIs. Recent studies indicate that HRT has a small detrimental effect on cognitive function and is associated with a doubling of the incidence of dementia. A comprehensive study of the SERM, raloxifene, on cognitive function showed no significant effect. There are no definitive reported studies investigating tamoxifen and none for AIs on cognitive function, although there is one in progress in the context of the IBIS II prevention trial which compares anastrozole to placebo in women at high risk. At present concerns about deleterious vascular side effects are confined to HRT and SERMs. However, we have few long-term data using AIs for the treatment and prevention of breast cancer.
Affiliation:
CRUK Department of Medical Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. anthony.howell@christie-tr.nwest.nhs.uk
Citation:
Vascular effects of aromatase inhibitors: data from clinical trials. 2005, 95 (1-5):143-9 J. Steroid Biochem. Mol. Biol.
Journal:
The Journal of Steroid Biochemistry and Molecular Biology
Issue Date:
May-2005
URI:
http://hdl.handle.net/10541/76575
DOI:
10.1016/j.jsbmb.2005.04.005
PubMed ID:
15936188
Type:
Article
Language:
en
ISSN:
0960-0760
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHowell, Anthony-
dc.contributor.authorCuzick, Jack-
dc.date.accessioned2009-08-06T15:21:46Z-
dc.date.available2009-08-06T15:21:46Z-
dc.date.issued2005-05-
dc.identifier.citationVascular effects of aromatase inhibitors: data from clinical trials. 2005, 95 (1-5):143-9 J. Steroid Biochem. Mol. Biol.en
dc.identifier.issn0960-0760-
dc.identifier.pmid15936188-
dc.identifier.doi10.1016/j.jsbmb.2005.04.005-
dc.identifier.urihttp://hdl.handle.net/10541/76575-
dc.description.abstractAromatase inhibitors (AIs) are becoming the endocrine treatment of first choice for postmenopausal women with hormone receptor-positive breast cancer and are under investigation for use in breast cancer prevention. AIs reduce circulating estrogen to barely detectable concentrations. It is possible that such a low concentration will be deleterious to the vascular system since estrogen receptors are known to be in the cell walls of blood vessels and estrogen is thought to be important in maintaining blood vessel integrity. Because most women who present with primary breast cancer are cured by surgery and systemic therapy and the major cause of female death is vascular disease, it is particularly important to investigate the vascular side effects of AIs in current breast cancer adjuvant and prevention trials. In order to set the vascular toxicities of AIs reported in the current adjuvant trials into context, here we compare them with the toxicities seen during treatment with hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs). Clinical trial evidence indicates that HRT increases risk of coronary heart disease (CHD) whereas SERMs and AIs (to date) appear to be neutral. Cerebrovascular disease and venous thromboembotic events are increased by HRT and SERMs but appear to be unaffected by treatment with AIs. Cognitive function is also considered here since it may also have a vascular component and is potentially a serious potential side effect/benefit of AIs. Recent studies indicate that HRT has a small detrimental effect on cognitive function and is associated with a doubling of the incidence of dementia. A comprehensive study of the SERM, raloxifene, on cognitive function showed no significant effect. There are no definitive reported studies investigating tamoxifen and none for AIs on cognitive function, although there is one in progress in the context of the IBIS II prevention trial which compares anastrozole to placebo in women at high risk. At present concerns about deleterious vascular side effects are confined to HRT and SERMs. However, we have few long-term data using AIs for the treatment and prevention of breast cancer.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subject.meshAntineoplastic Agents, Hormonal-
dc.subject.meshAromatase Inhibitors-
dc.subject.meshBreast Neoplasms-
dc.subject.meshClinical Trials as Topic-
dc.subject.meshFemale-
dc.subject.meshHormone Replacement Therapy-
dc.subject.meshHumans-
dc.subject.meshLipid Metabolism-
dc.subject.meshSelective Estrogen Receptor Modulators-
dc.subject.meshVascular Diseases-
dc.titleVascular effects of aromatase inhibitors: data from clinical trials.en
dc.typeArticleen
dc.contributor.departmentCRUK Department of Medical Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. anthony.howell@christie-tr.nwest.nhs.uken
dc.identifier.journalThe Journal of Steroid Biochemistry and Molecular Biologyen
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