Soy and Breast Cancer.

Protection May Vary by Dose and Age

Soy foods, rich in plant estrogens, have been embraced by American women seeking relief from menopause without the breast cancer risk associated with synthetic hormones. Because Asian women consume diets but have a low incidence of breast cancer, it been suggested that soy prevents cancer, perhaps by reducing estrogen levels. Asian women living in Asia have serum estrogen levels as much as 40% lower than U.S. women and demonstrate a fivefold lower risk of developing breast cancer.

The link between soy and cancer prevention is far from conclusive, though, as Kerrie B. Bouker and Leena Hilakivi-Clarke of Georgetown University's Lombardi Cancer Center in Washington, DC, demonstrate with their summary of research on soy's effects on the breast [EHP 108:701-708]. The researchers suggest that for postmenopausal women in the United States, soy may actually have estrogenic effects.

Soy's assumed anticancer potential is associated with its rich supply of phytoestrogens, particularly genistein. A number of in vitro studies have shown genistein to suppress estrogenic activity, possibly by inhibiting estrogen-metabolizing enzymes. Animal experiments and studies with human breast cancer cells have demonstrated genistein's capacity to repress cell growth. Yet in vivo and in vitro models have also shown genistein to be estrogenic. Genistein is structurally similar to steroidal estrogens and binds to estrogen receptors, Like estrogen, it also helps build bone density, improves lipid profiles, and may reduce the risk of heart disease.

The paradox of genistein's estrogenic and antiestrogenic properties may be related to dose. Studies show that doses higher than can be achieved only by consuming soy-based foods provide protection against breast cancer similar to the drug tamoxifen. At doses achievable by consuming foods high in soy, genistein stimulates the growth of human breast cancer cells. However, a study of postmenopausal American women given 38 grams of soy protein isolate daily for 5 months (the amount they would get in a high-soy diet) showed no changes.

Genistein's effect also may depend on a woman's age during exposure. Rat studies show that in utero exposure to genistein but not to soy increases the risk of breast cancer. Another vulnerable stage for genistein exposure appears to be the years following menopause; animal studies with ovariectomized mice (a model of postmenopause) suggest that genistein increases breast cancer risk. However, no increase in risk is seen in animals exposed during their reproductive stage, and rats exposed to genistein before puberty show low breast cancer risk.

Asian women, however, eat a soy-based diet throughout pregnancy without raising their daughters' risk. Bouker and Hilakivi-Clarke speculate that Asian women's protection stems from their lifelong exposure. They also suggest that other components of soy such as saponins and phytic acids may temper genistein's estrogenic effects in humans.

The researchers theorize that genistein's varying effects may be a function of women's estrogen levels. When levels are low, as before puberty, genistein may act as an estrogen. Animal and human studies suggest that estrogen exposure before puberty paradoxically reduces breast cancer risk. The researchers also suggest that the phytoestrogen promotes the proliferation of mammary cells in women of all ages, but that because older women may already have malignant cells in their breasts, they're more likely to develop cancer.

In light of evidence suggesting that genistein may promote cancer, Bouker and Hilakivi-Clarke call for more studies of its effects. They believe explanations for the phytoestrogen's dual nature are close at hand.