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STUDY: Tamoxifen makes breast cancer more likely to be aggressive


WASHINGTON (AP) _ Tamoxifen is a powerful drug that lowers the overall risk of tumors recurring in breast cancer patients. But a new study shows that if a new cancer does develop it is five times as likely to be of an aggressive type.

Researchers at the Fred Hutchinson Cancer Research Center in Seattle report that they found clear evidence that tamoxifen significantly lowers the risk of new disease, but the study also demonstrates the need to find drugs that are effective against tumors resistant to tamoxifen.

``Half of the women who take tamoxifen develop resistance, but this resistance is not understood,'' said Dr. Christopher Li of the Hutchinson Center. He said the new study, appearing Wednesday in the Journal of the National Cancer Institute, is consistent with a theory that tamoxifen supports the growth of breast tumors that are not sensitive to estrogen, the female hormone.

This is important, said Li, because tamoxifen and other drugs work against tumors sensitive to estrogen, but ``there are no drugs that target estrogen-negative tumors.''

The study, he said, emphasizes the need for finding such drugs.

Dr. Sandra Swain of the National Cancer Institute said Li's study had ``noteworthy limitations'' and was inconsistent, in some respects, with other tamoxifen studies.

``The use of tamoxifen should not be changed based on this study,'' Swain said in an interview. ``Tamoxifen has clearly increased survival for thousands of women who have used it.''

Li agreed, but insisted that his study gives more insight into the effect of tamoxifen resistance among some breast cancer patients.

Estrogen, the female hormone, encourages the growth of some breast cancer cells. Tamoxifen interferes with this action of estrogen by attaching itself to the molecule, or receptor, on a cancer cell surface that is also used by estrogen. This, in effect, blocks the estrogen effect on the cancer cells. Cancer cells without an estrogen receptor are not affected by tamoxifen.

In the study, Li and his colleagues reviewed the medical history of almost 9,000 breast cancer patients. About half of the patients took tamoxifen as a follow-up to their primary treatment, such as surgery, radiation or both. The other half did not take tamoxifen.

After eight years, the researchers found that 89 of the tamoxifen users developed cancer in the breast previously unaffected, while such tumors were found in 100 who did not use tamoxifen.

Tamoxifen users had about a 10 percent overall reduced risk of developing tumors in the unaffected breast, the study showed.

However, among the non-tamoxifen users who developed second tumors, only 4 percent developed the more aggressive estrogen-negative cancer. Among the tamoxifen users, 27 percent of the second tumors were estrogen-negative. Li said that a statistical adjustment for the data shows that tamoxifen users were 4.9 times more likely to get the more aggressive breast cancer in the second breast than were the non-tamoxifen users.

Li said the conclusions need to be verified by other researchers, but he emphasized that despite the finding, tamoxifen is still a powerful drug for generally lowering the risk of breast cancer recurrence.

Other studies have shown that women who used tamoxifen for five years or more had a 47 percent reduction of recurrence. Li's study did not include the duration of tamoxifen use.

``I do not believe this study should change the clinical practice in regards to tamoxifen,'' he said. ``Tamoxifen does reduce the risk of a new cancer and it does improve the chances of survival.''
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