Isoflavone genistein may negate effect of common breast cancer drug

CHAMPAIGN, Ill. — Isoflavone-enhanced dietary supplements containing genistein may negate the tumor-fighting effects of tamoxifen, a commonly prescribed medication for women battling estrogen-dependent breast cancer, according to new findings appearing in the May 1 issue of the journal Cancer Research.

The research was led by William G. Helferich, a professor of food science and human nutrition at the University of Illinois at Urbana-Champaign.

In a pre-clinical study, researchers divided 66 mice, with their ovaries removed, into six groups to monitor the effects of estrogen and various amounts of tamoxifen and genistein, an estrogen-like component found in legume plants. Estrogen and tamoxifen implants were put into the mice, and estrogen-dependent breast cancer cells were injected. Before adding genistein to the diet, the tamoxifen had stopped tumor growth. The addition of genistein resulted in enhanced growth of estrogen-dependent tumors and increases in estrogen-responsive gene markers.

Blood concentrations of genistein in these mice were similar to those levels that people can get by consuming isoflavone-rich dietary supplements, Helferich said.

"Previous studies in rodents have suggested that exposure to genistein early in life may prevent or delay breast cancer," Helferich said. However, in a series of studies published last year, Helferich's laboratory demonstrated that various dietary products containing genistein can stimulate the growth of estrogen-dependent human breast tumors implanted into adult mice.

"This new study takes our previous findings a step further," Helferich said. "These results raise concern about consuming dietary isoflavone supplements in conjunction with tamoxifen in postmenopausal women who have estrogen-dependent breast cancer."

"This study also applies to women who are self-medicating with dietary estrogenic supplements by showing the supplements could negate the protective benefit of tamoxifen," he added.

Postmenopausal women with estrogen-dependent breast cancer often face an emotional roller coaster. Physicians prescribe tamoxifen to suppress the tumors and recommend against the use of hormone-replacement therapy (HRT). While tamoxifen stops estrogen from stimulating breast cancer cells, it also can cause menopausal symptoms. Unknown to their physicians, some women turn to over-the-counter products containing isoflavones as an alternative to HRT to treat their menopausal symptoms.

Genistein often is identified as one of several desired isoflavones in soy products, including soy-enhanced drinks and dietary supplements. Dietary isoflavones also can be found in both subterranean and red clover supplements.

Isoflavones in soy are believed to be responsible for anti-cancer effects observed in numerous human and animal studies. For example, in Asia, where cancer rates are low, people often consume diets rich in soy products that contain about 20 to 30 milligrams of isoflavones a day, Helferich said. However, many isoflavone-enhanced drinks and supplements now available in the United States may contain 30 to 150 milligrams per serving, and two or more servings a day are recommended on the labels, he added.

Other researchers contributing to the study were Young H. Ju, Kimberly F. Allred and Clinton D. Allred, all of the department of food science and human nutrition at Illinois, and Daniel R. Doerge of the National Center for Toxicological Research in Jefferson, Ark.

The National Institutes of Health funded the research through a grant to Helferich.

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