Document Detail


Tamoxifen resistance in breast cancer.
MedLine Citation:
PMID:  8397846     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tamoxifen (TAM) resistance is the underlying cause of treatment failure in many breast cancer patients receiving TAM. The mechanism(s) involved in TAM resistance are poorly understood. A variety of mechanisms have been proposed but only limited evidence exists to substantiate them. Studies have now shown that in many patients TAM resistance is not related to the down regulation or loss of estrogen receptors (ER). Variant ER have been identified, but their significance clinically remains to be proven. Since breast cancer cells secrete several estrogen-regulated growth factors and growth inhibitors that may have autocrine or paracrine activity, altered growth factor production is another possible mechanism for TAM resistance. Tissue-specific transcription activating factors that may alter how the signal induced by TAM binding to the receptor is interpreted by the cell also require further investigation. An increase in antiestrogen binding sites (AEBS), which could effectively partition TAM and reduce its concentration at the ER has also been proposed as a potential mechanism. Pharmacologic mechanisms, such as a shift in metabolism toward the accumulation of estrogenic metabolites, are supported by recent data demonstrating metabolite E and bisphenol in tumors from TAM-resistant patients. Furthermore, a decrease in tumor TAM accumulation and an altered metabolite profile have been reported in TAM-resistant breast tumors grown in nude mice. These and other studies suggest that TAM resistance may be multifactorial in nature, but definitive identification of mechanisms that are operative in clinical TAM resistance requires further study.
Authors:
V J Wiebe; C K Osborne; S A Fuqua; M W DeGregorio
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Critical reviews in oncology/hematology     Volume:  14     ISSN:  1040-8428     ISO Abbreviation:  Crit. Rev. Oncol. Hematol.     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-11-19     Completed Date:  1993-11-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8916049     Medline TA:  Crit Rev Oncol Hematol     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  173-88     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / drug therapy*
Drug Resistance
Female
Humans
Receptors, Estrogen / drug effects
Tamoxifen / adverse effects,  metabolism,  pharmacology*
Grant Support
ID/Acronym/Agency:
NCI P50 CA58183/CA/NCI NIH HHS; NCI R-01 CA 30251/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Estrogen; 10540-29-1/Tamoxifen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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