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Old 06-15-2004, 11:07 PM   #1
christine
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Study Investigates Breast Cancer Resistance to Tamoxifen and Possible Way
to Reverse It

Sarah L. Zielinski
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute

A new study has found a possible mechanism for tamoxifen resistance in
breast cancer and provides evidence that another cancer drugĂ‚Â*gefitinib
(Iressa)Ă‚Â*may be able to restore tamoxifen’s anticancer activity. The study
appears in the June 16 issue of the Journal of the National Cancer Institute.

Although adjuvant tamoxifen can reduce the risk of death for women with
invasive breast cancer by about 15% over 10 to 15 years many women do not
receive any benefit from the drug. Even among patients most likely to
benefit from tamoxifenĂ‚Â*those with tumors that express the drug’s target
the estrogen receptor (ER)Ă‚Â*only 40% to 50% actually benefit. Studies have
shown that patients with ER-positive tumors that express high levels of
HER2/neu and the ER coactivator AIB1 often develop tamoxifen resistance
but the mechanism of the resistance has not been identified.

To find this mechanism Rachel Schiff Ph.D. of the Baylor College of
Medicine in Houston and colleagues studied molecular interactions in
breast cancer cells that expressed high levels of both HER2 and AIB1. They
found that in these cells tamoxifen acted like an estrogen agonist and
stimulated tumor growth. However when the breast cancer cells were treated
with the receptor tyrosine kinase inhibitor gefitinib tamoxifen once again
acted as an estrogen antagonist and tumor growth was blocked.

"Our data imply that monotherapy with growth factor pathway inhibitors like
gefitinib may have little or only modest benefits on ER-positive
HER2-overexpressing breast cancer but the results do provide a strong
rationale for combining tamoxifen with gefitinib or other EGFR/HER2 pathway
inhibitors to overcome ... resistance in such tumors. Clinical trials of
this new strategy are under way " the authors write.

In an editorial Daniel F. Hayes M.D. of the University of Michigan
Health System in Ann Arbor reviews tamoxifen’s potential for both harm and
good in breast cancer patients. "It is imperative that we now take
advantage of the advances in understanding of the biology of these ...
systems to efficiently select optimal treatment and even further reduce
mortality of patients with breast cancer " he writes adding that "[t]hese
steps can only be taken by conducting well-designed clinical trials."

###

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