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Researchers Uncover Cause Of Tamoxifen Resistance

Posted by Chrissie Cole
Wednesday, November 12, 2008 10:37 PM EST
Category: Major Medical
Tags: FDA and Prescription Drugs, Tamoxifen, Nolvadex, AstraZeneca, Breast Cancer, Women's Health

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IMAGE SOURCE:© Wikimedia Commons / tamoxifen molecule /author: Benjah-bmm27


As many as 35 percent of women who take the drug tamoxifen to prevent the recurrence of breast cancer do not respond to the drug -- and scientists think they have figured out why.

Women who don’t benefit from tamoxifen, used to prevent breast cancer recurrence, may have low levels of a protein linked to improved survival, finds U.K. researchers.

About 45,000 cases of breast cancer are diagnosed in the UK each year and almost 12,500 die from the disease. Up to two-thirds of those women will be prescribed tamoxifen. Ideally, women take it for five years after their diagnosis.

Tamoxifen is given to up to 28,000 of the 45,000 women who develop breast cancer each year, to help prevent cancer recurrence after surgery to remove a tumor.

But in up to 35 percent of cases, or 9,000 women, the drug does not work properly and the disease returns.

Tamoxifen works by turning off a breast cancer gene ErbB2, through the protein PAX2, researchers said.

“Understanding how tamoxifen works and what happens when it fails to work as intended is critical to making better drugs,” Jason Carroll, from the Cancer Research UK Cambridge Research Institute said.

For the study, researchers used microarrays -- gene chips -- to scan millions of DNA sequences to examine what was happening in those genes known to play a key role in breast cancer.

For the drug to work effectively it must block a cancer gene called HER2, which it does by using a control switch hidden within the gene.

But, for this to happen a protein called Pax2 must keep the switch in the off position -- which fails for women who develop resistance to the drug, the researchers said.

Tamoxifen Citrate, sold under the brand name Nolvadex, is commonly used in conjunction with radiation to treat breast cancer. Nolvadex blocks some of the effects that the hormone estrogen has on the body. The Food & Drug Administration approved it for treatment of breast cancer in 1994. In October 1998, it was approved for use in women at high risk of developing breast cancer.

Larger studies are needed to replicate findings before they can be considered conclusive. Drug companies and researchers can then start developing treatments that target these proteins, said Carroll in a conference call.

The findings could be used to help researchers predict which patients are likely to respond to the drug and which are not.

“If we can identify the women who are not going to respond to tamoxifen, we can consider alternative therapies which will most likely be more effective for these women,” Carroll said.

The study is published in the November 12 online edition of Nature.


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