NASHVILLE, Tenn. -- Vanderbilt Cancer Center researchers have reported a discovery that could help overcome a major obstacle in treating breast cancer with tamoxifen -- the resistance that breast tumor cells commonly develop to this "anti-estrogen" drug.

Writing in the Jan. 6 issue of the Journal of the National Cancer Institute, the researchers report that overproduction of a certain growth factor, called TGF-beta, contributes to tamoxifen resistance. They also demonstrate that the immune system's "natural killer" activity is important for tamoxifen's anti-cancer effects.

Ultimately, both findings might be exploited to keep tumors dormant for longer periods using tamoxifen.

"At some point in the natural history of breast cancer, tumors become resistant to the anti-estrogen tamoxifen," said principal investigator Dr. Carlos L. Arteaga, professor of Medicine and associate professor of Cell Biology.

"The practical implication of this research is that, if we can sort out the mediators of this effect, perhaps we can design strategies to interfere with those mechanisms and markedly prolong the period of tamoxifen response or even reverse tamoxifen resistance."

Tamoxifen, a relatively well-tolerated therapy, has been a part of the arsenal against advanced breast cancer for more than two decades. More recently, it has been used as an additional therapy following surgery or other primary treatment for early stage breast cancer. Tamoxifen is also being studied as a "chemopreventive" to delay the onset of breast cancer in women at high risk of developing the disease.

The drug is called an anti-estrogen because it blocks the effects of the female hormone estrogen. Some breast cancer cells are sensitive to estrogen, which binds to estrogen receptors in these cells and stimulates them to proliferate and invade.

In patients with metastatic breast cancer, tumors typically become resistant to tamoxifen in about 12-18 months, Arteaga said.

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Contact: Cynthia Manley
cynthia.manley@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
6-Jan-1999