British Study Shows Possible Explanation For Tamoxifen Resistance In Some Breast Cancer Patients

Main Category: Breast Cancer
Article Date: 17 Nov 2008 - 8:00 PST

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British researchers have discovered a possible explanation for why some female breast cancer patients being treated with tamoxifen -- the most commonly used breast cancer drug -- are resistant to the treatment, increasing their risk that tumors will return, according to a study published in the journal Nature, Reuters/New York Times reports. According to Reuters/Times, most women are given tamoxifen for five years after breast cancer diagnosis to prevent recurrence of the disease. The drug works by blocking a hidden "switch" within a certain gene (Her2) and preventing estrogen from causing cell growth in breast cancer, "but how exactly this happened was unknown," Reuters/Times reports.

For the study, researchers used microarrays -- or gene chips -- to examine millions of DNA sequences and investigate what was occurring in genes that are known to play a central role in breast cancer. The researchers discovered that a protein called Pax2 is necessary to prevent the Her2 gene from activating (Reuters/New York Times, 11/13). The study, which involved 100 breast cancer patients, showed that the highest levels of Pax2 were associated with improved survival rates. However, tamoxifen-resistant tumors had higher levels of AIB-1, another molecule that competes with Pax2 for control of Her2. Researchers found that the winning molecule determines if Her2 is switched on or off, (BBC News reports. Lead researcher Jason Carroll of Cancer Research UK said the failed switch would not account for all cases of tamoxifen resistance but that he believes it will "account for quite a significant number." He also said that women who are resistant to tamoxifen should receive other drugs, such as Herceptin, or a group of medicines called aromatase inhibitors (BBC News, 11/13).

According to Carroll, the results of the study could guide the creation of new tests to determine if breast cancer patients will be resistant to tamoxifen and should be given other drugs to treat the disease. "More importantly, it gives us an idea of what we should be making drugs against," he said (Reuters/New York Times, 11/13). Carroll said a test for tamoxifen resistance based on the study could occur within five years, according to the AP/Yahoo! News (AP/Yahoo! News, 11/12). Alexis Willett, a physician with Breakthrough Breast Cancer, said the study is an "important step towards developing improved treatments for patients" and gives researchers a "better understanding of one of the ways resistance can occur." David Lane, Cancer Research UK's chief scientist, said that using tamoxifen to treat breast cancer patients has been a "huge success story." He added, "Understanding why it occasionally stops working is really important because it allows us to identify new targets for drug development and who will need such treatments" (BBC News, 11/13).

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