WASHINGTON (AP) - Tamoxifen, a drug that fights breast cancer by blocking the action of the hormone estrogen, eventually loses its effectiveness and then actually may help the cancer grow, researchers say.
In a study to be published Friday in the journal Science, scientists at Duke University Medical Center said they have found that the reaction of breast cells to tamoxifen changes over time until the drug starts to behave like the hormone it is supposed to block.
Estrogen has been shown to promote the growth of about half of breast cancers. Tamoxifen blocks this action by preventing estrogen from linking up to a receptor on the surface of cells.
But clinical experience has shown that after two to five years, the anti-estrogen effect of tamoxifen fades, often allowing estrogen-sensitive cancers to start growing again. Researchers have been puzzled about why this tamoxifen resistance occurs.
Now researchers at Duke may have the answer.
Dr. John D. Norris, first author of the study, said that an analysis of the tamoxifen action showed that, over time, the drug causes the estrogen receptor on cells to change and form a pocket-like structure that allows other proteins to bind there. The action of these proteins somehow changes the cell's reaction to tamoxifen. The drug converts from an anti-estrogen effect to a pro-estrogen effect.
''The cells learn how to recognize that new receptor shape as estrogen,'' said Norris. ''We're not sure why.''
Norris said the research shows that tamoxifen resistance can be reversed using peptides that block the pocket-like structures on the cell receptor. This causes tamoxifen to once again have an anti-estrogen effect.
He said the new understanding could also help researchers find a new anti-estrogen drug that does not produce the cell receptor reshaping that is caused by tamoxifen.
Estrogen is a double-edged sword in the health of women. While its presence has been shown to promote breast and uterine cancer, the hormone also has been shown to be protective against osteoporosis and heart disease.
Tamoxifen is a widely used drug for breast cancer because it blocks the cancer-promoting action of estrogen in breast tissue, while having a beneficial estrogen-like effect in the bones.