Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO Subscriptions PDA Services My JCO Customer Service

Originally published as JCO Early Release 10.1200/JCO.2007.11.3886 on September 24 2007

Journal of Clinical Oncology, Vol 25, No 36 (December 20), 2007: pp. 5815-5824
© 2007 American Society of Clinical Oncology.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jordan, V. C.
Right arrow Articles by O'Malley, B. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jordan, V. C.
Right arrow Articles by O'Malley, B. W.

BIOLOGY OF NEOPLASIA

Selective Estrogen-Receptor Modulators and Antihormonal Resistance in Breast Cancer

V. Craig Jordan, Bert W. O'Malley

From the Fox Chase Cancer Center, Philadelphia, PA; and Baylor College of Medicine, Houston, TX

Address reprint requests to V. Craig Jordan, OBE, PhD, DSc, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111-2497; e-mail: v.craig.jordan{at}fccc.edu

Selective estrogen-receptor (ER) modulators (SERMs) are synthetic nonsteroidal compounds that switch on and switch off target sites throughout the body. Tamoxifen, the pioneering SERM, blocks estrogen action by binding to the ER in breast cancers. Tamoxifen has been used ubiquitously in clinical practice during the last 30 years for the treatment of breast cancer and is currently available to reduce the risk of breast cancer in high-risk women. Raloxifene maintains bone density (estrogen-like effect) in postmenopausal osteoporotic women, but at the same time reduces the incidence of breast cancer in both high- and low-risk (osteoporotic) postmenopausal women. Unlike tamoxifen, raloxifene does not increase the incidence of endometrial cancer. Clearly, the simple ER model of estrogen action can no longer be used to explain SERM action at different sites around the body. Instead, a new model has evolved on the basis of the discovery of protein partners that modulate estrogen action at distinct target sites. Coactivators are the principal players that assemble a complex of functional proteins around the ligand ER complex to initiate transcription of a target gene at its promoter site. A promiscuous SERM ER complex creates a stimulatory signal in growth factor receptor–rich breast or endometrial cancer cells. These events cause drug-resistant, SERM-stimulated growth. The sometimes surprising pharmacology of SERMs has resulted in a growing interest in the development of new selective medicines for other members of the nuclear receptor superfamily. This will allow the precise treatment of diseases that was previously considered impossible.

published online ahead of print at www.jco.org on September 24, 2007.

Supported by the Department of Defense Breast Program under award number BC050277 Center of Excellence, SPORE in Breast Cancer CA 89018, R01 GM067156, FCCC Core Grant, NIH P30 CA006927, the Avon Foundation, and the Weg Fund of Fox Chase Cancer Center (V.J.C.); and National Institute of Health grants from the National Institute of Child Health and Human Development and National Institute of Diabetes and Digestive and Kidney Diseases, and Nuclear Receptor Signaling Atlas (B.W.O.).

Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.




This article has been cited by other articles:


Home page
JCOHome page
V. C. Jordan
The 38th David A. Karnofsky Lecture: The Paradoxical Actions of Estrogen in Breast Cancer--Survival or Death?
J. Clin. Oncol., June 20, 2008; 26(18): 3073 - 3082.
[Abstract] [Full Text] [PDF]



About
JCO
 Editorial
Roster
 Advertising
Information
 Librarians &
Institutions
 Rights &
Permissions
 Site Map

Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online