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Researchers Study Which Breast Cancer Patients are Most Likely to Benefit from Tamoxifen (dateline June 28, 2003)

While the drug tamoxifen can be very effective at helping to treat breast cancer, researchers know that tamoxifen does not work well in all patients. Previous research has shown that women with certain types of breast cancer, specifically those that are not estrogen sensitive, do not typically benefit from tamoxifen. Now, researchers have uncovered more information about tamoxifen. In a recently published study, Baylor College researchers report that certain proteins seem to "deactivate" the positive effect of tamoxifen in some women whose cancers are estrogen sensitive. The research may lead to more effective treatments that target these proteins.

Tamoxifen is a drug taken orally in pill form. For over twenty years, physicians have prescribed tamoxifen to help treat patients with advanced breast cancer. More recently, tamoxifen has been used as to treat early stage breast cancer after surgery. Tamoxifen has been shown to help prevent the original breast cancer from returning after breast surgery while also hindering the development of new cancers in the opposite breast.

Approximately 80% of women who are diagnosed with breast cancer have estrogen-receptor positive breast cancers (also called estrogen sensitive cancers). That is, their breast cancer cells contain estrogen receptors. Tamoxifen fights estrogen sensitive cancers particularly well because the drug binds to the estrogen receptors, preventing estrogen from reaching the cancer cells. Because these cancer cells depend on estrogen for survival, a lack of estrogen starves them. While tamoxifen works well in estrogen-receptor positive breast cancers, it is typically less beneficial in women with estrogen-receptor negative breast cancers (i.e., cancers that do not contain estrogen receptors). Researchers have been focused on trying to discover why this is the case. For the meantime, women with estrogen-receptor negative breast cancer do not typically receive tamoxifen.

Yet tamoxifen does not work well in all women with estrogen-receptor positive breast cancers either. To determine whether certain levels of proteins present within breast cancer cells can affect the performance of tamoxifen, Dr. C. Kent Osborne and colleagues from Baylor College of Medicine studied breast cancer tumors of 316 women who all had been diagnosed with estrogen-receptor positive breast cancers. In particular, they searched for two proteins, HER2 and AIB1 (also called SRC-3).

Researchers have previously found that women whose breast cancers contain an overabundance of HER2 proteins tend to have aggressive diseases. This research has led to the development of a promising drug, Herceptin, to help treat cancers that contain too many HER2 proteins. Some research has shown that cancers with high levels of HER2 may be resistant to tamoxifen, but data are mixed.

When Dr. Osborne and colleagues analyzed the breast cancer tumors in their study, they found that those cancers with high levels of both HER2 and the AIB1 proteins tended to respond poorly to treatment with tamoxifen, suggesting that the proteins interfere with the drug’s activity. In fact, women who had high AIB1 levels and did not receive tamoxifen fared better (survived for longer periods of time and remained cancer free for longer intervals) than those women with high AIB1 levels who took tamoxifen.

The research suggests that determining AIB1 levels in breast cancer patients is important in predicting which patients will respond well to tamoxifen and which patients need not take the drug. Furthermore, medicines that specifically target the AIB1 protein could be an important advance in breast cancer treatment, similar to the drug Herceptin that targets the HER2 protein. Future studies of the AIB1 and HER2 proteins will help researchers better understand their roles and how they might figure into the development of new treatments.

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