Tamoxifen, a drug used to treat breast cancer, can be extremely helpful to some women but have no effect, or even a harmful effect, on others. Doctors prescribe tamoxifen for women who have estrogen-receptor-positive cancer, meaning that the cancer growth is controlled by the hormone estrogen, which is the case in about two thirds of all breast cancer tumors. Tamoxifen can inhibit the growth of these kinds of tumors in about half the cases but in the other half seems to do nothing. Doctors from the Baylor College of Medicine in Texas studied the differences in estrogen-receptor-positive tumors in order to find out if there is a way to make tamoxifen more effective.

What the researchers wanted to know: Why does tamoxifen shrink certain types of estrogen-receptor-positive breast cancers and not others?

What they did: Previously, the authors had reported that patients who have high levels of HER2/neu, a growth hormone, and AIB1, a compound that works with estrogen, have higher rates of relapse after taking tamoxifen. In this current study, they looked at how cancer cells that have a lot of these two compounds interact with tamoxifen. The doctors grew tumors with high levels of HER2/neu and AIB1 in mice. The tumors were removed and treated with tamoxifen or with tamoxifen plus another cancer drug called gefitinib.

What they found: The scientists found that, used alone, tamoxifen actually stimulated growth in cancer cells with high levels of HER2/neu and AIB1. However, when the scientists treated those cells with gefitinib, the drug let tamoxifen inhibit the growth of tumors the way it's supposed to. A breast cancer specialist from the University of Michigan who wrote an accompanying editorial about the project compared tamoxifen to Dr. Jekyll and Mr. Hyde—in some cases, shrinking tumors and saving lives; in others, making the tumors grow bigger.

What it means to you: This research was done on mice, so human trials and approval of this therapy have yet to take place, but this could make tamoxifen much more useful against a common type of breast cancer.

Caveats: There's no guarantee that what works on mice will work in people. Also, the doctors used only one type of cancer cell in their experiment when, in reality, cancer is made of many different types of cells, which respond differently to drugs.

Find out more: Information about different drugs, including tamoxifen and gefitinib, cataloged under its brand name, Iressa, is available through the Food and Drug Administration's Center for Drug Evaluation and Research. More about how tamoxifen and estrogen affect the growth of breast cancer can be found on a variety of websites. A good, concise explanation comes from the National Cancer Institute.

Read the article: Shou, J., Massarweh, S., Osborne, C.K., Wakeling, A.E., Ali, S., Weiss, H. and R. Schiff. "Mechanisms of Tamoxifen Resistance: Increased Estrogen Receptor-HER2/neu Cross-Talk in ER/HER2-Positive Breast Cancer." Journal of the National Cancer Institute. June 16, 2004, Vol. 96, No. 12, pp. 926–935.

Abstract online: http://jncicancerspectrum.oupjournals.org

An editorial accompanying the article by Daniel F. Hayes is also available in this issue of the magazine or free online at http://jncicancerspectrum.oupjournals.org.