Soy and Human Health

• The Astonishing Functional Food: Soy Protein and Soy Constituents
• Soy Protein and Coronary Heart Disease
• Soy and Digestive Tract Health
• Soy Foods in Chronic Renal Disease
• How Can Soy Help Diabetes?
• Soy Protein Enhances Energy, Stamina and Sport Performance
• Soy and Cancers
• Soy and Breast Cancer
• Soy and Menopausal Symptoms
• Soy and Pre-Menstrual Syndromes
• Soy and Bone Health
• Losing Weight Healthily with Soy
• Soy and Urological Cancer
• Soy Lecithin and Human Health
• Clinical Abstracts on Soy
• Soy Clinical Reviews in Reputable Medical Journals: 1995-2002

Soy and Breast Cancer

According to the United States National Cancer Institute, women who live to be 90 years old have a 1 in 8 risk of being diagnosed with breast cancer. Breast cancer is expected to be the most frequently diagnosed non-skin malignancy in U.S. women, second to lung cancer.

For all ages of women, white women are more likely to develop breast cancer than African-American women, although under age 50 African-American women have higher incidence rates than white women (American Cancer Society, 2000).

There are many risk factors of breast cancer of which increases with age and is higher in women with: a family/personal history of breast cancer; early menarche; late menopause; recent use of postmenopausal estrogens or oral contraceptives; atypical cell growth; first live birth at a late age or no children; and higher education and socioeconomic status. Other possible risk factors include weight gain, physical inactivity, high fat intake, alcohol consumption, pesticide/chemical exposure, and induced abortion.

Soy contains a variety of anti-cancer agents including protease inhibitors, phytate, phytosterols, saponins, and the isoflavones, as well as other possible anticarcinogens such as phenolic acids, lecithin and omega-3 fatty acids. Of these, the isoflavones are currently the most intensively researched soy phytochemical with respect to breast cancer. In addition, certain protease inhibitors, such as the Bowman-Birk inhibitor (BBI) found in soy, have been shown to prevent and suppress malignant transformation in vitro and carcinogenesis in animal models without toxicity.

North American Menopause Society’s Consensus Opinion on The Role of Isoflavones in Menopausal Health agreed that, epidemiologic, in vitro, and in vivo studies have shown both protective and stimulatory effects of soy and soy isoflavones on breast cancer (North American Menopause Society, 2000).

Soy isoflavones have been shown to be anticarcinogenic in several ways. First, they are very similar in structure to estrogen and are able to bind estrogen receptors (ER), though they exhibit only a weak estrogenic ?effect, only 1/100th to 1/1000th that of estradiol as regards binding to ER- However, preferential binding to a more recently discovered second receptor, suggest that nonsteroidal estrogens may exert their actions through ER- distinct pathways separate from classic steroidal estrogens. Isoflavones may work by binding estrogen receptors and blocking the harmful effects of the more potent form of estrogen, thus functioning as an overall antiestrogen.

A variety of other non-hormonal anti-cancer mechanisms have also been proposed. Genistein has been shown to inhibit growth of both human and rodent cancer cell lines in vivo and in vitro and one proposed mechanism is through its inhibition of certain enzymes that stimulate cancer cell growth such as protein tyrosine kinases. Genistein also induces differentiation of some malignant cells into benign cells, possibly interfering with carcinogenesis, and inhibits angiogenesis (the formation of new blood vessels) thus reducing the blood supply to growing tumors. Genistein also works as an antioxidant, preventing cell damage from free radicals and may also inhibit cancer cell growth by inducing changes in signaling pathways of transforming growth factor (TGF-1). The presence of isoflavones in soy may be why the incidence of breast cancer in Japan and China is one-fifth of that in Western women. The average intake of soy protein in Southeast Asia ranges from 10-50g per day in contrast to 1-3g per day consumed by Americans. Asian women consume 20-80 mg of isoflavones per day compared to women in the U.S. whose intake is less than 5mg per day.

One clinical trial currently underway at Northwestern University in Chicago involves 200 premenopausal women, some of which will consume 40g of soy protein isolate per day for 4 months after first spending a lead-in period of one year consuming a high-fiber, low-fat diet.

One recent study evaluated the effect of a soy product in combination with tamoxifen against mammary tumorigenesis in female rats. Tamoxifen reduced mammary tumors 29%, soy protein isolate (SPI) reduced mammary tumors 37%, and the combination of tamoxifen and SPI led to a 62% reduction in tumors. Authors note these finding suggest a human trial is warranted.

Many, but not all, of the epidemiological studies, which have specifically examined soy consumption and later incidence of breast cancer have shown that soy intake can be protective. In one study done in Singapore on 200 Singapore Chinese women with breast cancer and 420 matched controls, a decreased risk of breast cancer was associated with high intakes of soy products in premenopausal but not postmenopausal women.

A more recent case-control study done at the University of Southern California, Los Angeles, interviewed 597 Asian-American women with previous incidence of breast cancer and 966 controls. Risk of breast cancer decreased with increasing frequency of tofu consumption (but not with fried tofu) in both pre- and postmenopausal women.

In a new meta-analysis of 7 epidemiologic studies (5 case-control studies of Asian women living in Asian countries; 2 cohort studies of Asian-American women living in the US), a modest reduction of breast cancer was observed among all reports for the highest level of soy consumption compared with the lowest (OR=0.83, 95% CI=0.73-0.95). The protective association was in pre-menopausal women (OR=0.74, 95% CI=0.62-0.87). Although there was no apparent benefit among post-menopausal women (OR=0.94, 95% CI=0.79-1.12), it was noted that post-menopausal women who consumed greater amounts of soy, did not appear to be at increased risk of breast cancer.

An intake of soyfoods early in life may be important for its protective effect. In a case-control study of Chinese females involving 1,459 breast cancer cases and 1,556 age-matched It appears that genistein can act as both an estrogen and an antiproliferative agent. According to a recent review of genistein and breast cancer, these effects may be both dose and tissue dependent. In a recent review of animal studies published between 1990 and 1997, 16 of 17 studies (94%) showed that soy was protective, and five of these were in breast cancer models.

One of the most controversial topics of soy and breast cancer research is whether high concentrations of isoflavones may be contraindicated for post-menopausal women, who have a relatively low level of circulating estrogen. Hsieh et al (1998) found that dietary genistein stimulated the growth of MCF-7 (ER+ breast cancer) cells implanted subcutaneously into the skin of ovariectomized mice. In another study just published by this research group, soy protein isolate containing increasing concentrations of genistein (15, 150, or 300 ppm) stimulated growth of estrogen-dependent breast tumors in vivo in a dose-dependent manner in athymic (Allred et al., 2001). There are concerns, however, about extrapolating data from the athymic, ovariectomized nude mouse model to pre- or post-menopausal women.

Little data exists regarding the effects on the normal human breast, but two studies have raised some concerns. The first examined the effect of soy on the proliferation rate of premenopausal normal breast epithelium and found a significant increase after 14 days of soy supplementation of 60g/day containing 45mg isoflavones (McMichael-Phillips et al., 1998). However, this was a very short study and there are other events, such as pregnancy and breast-feeding, which cause mammary cell proliferation and are linked to a reduction, not an increase, in breast cancer risk. Furthermore, in a follow-up study by Hargreaves et al. (1999) that included all subjects (n=84), no effects on cell proliferation were found. A study by Petrakis et al (1996) also suggested that soy has an estrogenic effect on the breast. In 24 pre- and post-menopausal women consumed 38g/day of soy protein isolate (containing 38 mg of genistein) an increase in nipple aspirate fluid (NAF) was found in the pre-menopausal women; a minimal increase or no response was found in postmenopausal women. Also of concern was the appearance of hyperplasic epithelial cells in the NAF of 30% of the women, which has been found to be indicative of a modest increased risk of breast cancer. Although the study concluded that the prolonged daily consumption of soy protein isolate appeared to have a stimulatory effect on the premenopausal female breast, this was a poorly designed study with a number of design flaws, including lack of a control group.