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Protein Cripples Tamoxifen

Breast Cancer Drug May Not Work in Certain Women

WebMD Health News

March 4, 2003 -- The cancer-fighting potential of the popular drug tamoxifen, used to prevent breast cancer in women, may be determined by a certain protein found in breast cancer tumors. A new study shows the effectiveness of tamoxifen may be significantly reduced if a woman has high levels of a protein known as AIB1.

The study, published in the March 5 issue of the Journal of the National Cancer Institute, suggests that women who have breast cancer tumors that produce high levels of this protein are resistant to the protective effects of tamoxifen, which is commonly prescribed to prevent breast cancer recurrence.

Researchers say if further studies confirm these results, screening for AIB1 might help determine which women would benefit most from tamoxifen and which would benefit from alternative treatments.

Previous studies have already indicated that certain types of breast cancers, known as estrogen receptor-positive or ER-positive cancers, depend on estrogen to grow and spread.

Some of these ER-positive cancers also produce high levels of AIB1 as well as another protein called HER-2, but until now it wasn't clear whether AIB1 expression alone or in combination with HER-2 was responsible for reducing the effectiveness of tamoxifen.

In this study, researchers measured levels of both proteins in 187 women who received tamoxifen after initial breast cancer treatment and 119 women who did not receive additional treatment.

They found that women who did not receive tamoxifen and had high AIB1 levels had longer disease-free survival and better health. But women who received tamoxifen and had high AIB1 levels had worse disease-free survival.

Researcher C. Kent Osborne, MD, director of the Breast Center at Baylor College of Medicine in Houston, says those findings suggest that these women were resistant to the drug.

"In fact, tamoxifen might have an adverse effect," says Osborne in a news release.

In addition, women who were treated with tamoxifen and had both high HER-2 and AIB1 expression had much worse disease-free survival rates that all other groups combined.

When levels of either protein are low, the tamoxifen problems don't occur, writes Osbourne.

Researchers say the results suggest that levels of AIB1 expression in a breast cancer tumor might be a strong predictor of tamoxifen resistance. They say this protein may also play a role in the tamoxifen resistance found in women with high HER-2 levels, but these findings need to be confirmed by additional research.

In an editorial that accompanies the study, V. Craig Jordan, PhD, DSc, of Northwestern University Medical School, points out that only 10% of the women in the study were negatively affected by the proteins. But he writes that it is important to find out whether tumors with high levels of these proteins may respond to another drug, such as Arimidex, which is currently being compared with tamoxifen in clinical trials.

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