Perspectives on the soy-breast cancer relation

There has been considerable investigation of the potential for soy foods to reduce risk of breast cancer. Initial enthusiasm for this research was partially based on the historically low incidence rates of breast cancer and high soy food intake in Japan. There are several putative soybean chemopreventive agents, but most cancer research has focused on isoflavones. Isoflavones possess both hormonal and nonhormonal properties relevant to carcinogenesis. Recent epidemiologic analyses indicate that among Asians high soy intake is associated with an approximate one-third reduction in the risk of both pre- and postmenopausal breast cancer. However, several lines of evidence suggest that to derive maximum protection against breast cancer, soy must be consumed early in life. This evidence is consistent with the lack of significant effects noted in clinical studies that have evaluated the effects of isoflavone-containing products on breast cancer risk markers. Isoflavones may exert their putative protective effects by stimulating breast cell differentiation in a manner similar to that which is thought to occur during early pregnancy. Finally, the ability of the isoflavone genistein to stimulate the growth of mammary tumors in ovariectomized athymic nude mice implanted with estrogen-sensitive breast cancer cells has raised concern that soy foods, and especially isoflavone supplements, are contraindicated for patients with breast cancer and women at high risk of breast cancer. However, findings from clinical studies, in which breast biopsies have been taken or breast tissue density measured after isoflavone exposure, are reassuring and contrast with the proliferative effects of conventional combined hormone therapy, although understanding of the effect of soy and isoflavones on breast tissues remains imprecise. Am J Clin Nutr 2009; 89(suppl): 1673S-9S.