Soybeans are recommended for breast cancer

Soybean intake is increasing in the U.S. diet, but primarily through the consumption of soy protein isolate in processed foods, soybean oil, and soy-based animal and fish feed. This web page is intended to examine the impact of consuming less highly processed soy foods on breast cancer risk. Such foods include tofu, edamame and tempeh. Most of the population studies concerning the consumption of soy foods have been performed in Asian populations. This raises some question as to how applicable the results might be to non-Asian populations since Asians are more likely to convert soy phytoestrogens to potentially protective metabolites in the gut than Caucasians (see the genistein and daidzein webpage).

Breast cancer-related effects of consuming soybeans

As shown in the brief summaries below, studies of the impact of consuming non-highly processed soy foods on breast cancer risk are somewhat contradictory, but generally have found a protective effect against breast cancer. Several studies have also found that high soy food intake during childhood or adolescence may reduce the risk of breast cancer in later life.

A case-control study designed to examine the association between childhood soy intake and breast cancer risk in U.S. women of Asian (Chinese, Japanese, and Filipino) descent found inverse associations with childhood soy intake in all three groups and women born both in Asia and the U.S. The authors concluded that early-life exposure to soy may influence breast cancer incidence.
A study designed to compare insulin-like growth factor-I (IGF-I) levels in Japanese women in Japan and Japanese and Caucasians in Hawaii with high and low soy intake found that average IGF-I levels were 11% lower among women in the highest tofu consumption category compared with the lowest, but the difference in IGF-I levels between tofu consumption levels was only significant among women in Japan. IGF-I is thought to be a link between diet and breast cancer risk since high circulating levels of IGF-I appears to increase cell proliferation and reduce apoptosis. The average IGF-I levels were 213 for Japanese in Japan, 257 for Japanese in Hawaii, and 255 ng/ml for Caucasians in Hawaii. Tofu intake was higher in Japan than among either Hawaiian groups.
A case-control study designed to investigate the association between isoflavone intake and breast cancer risk among Japanese, Japanese Brazilians and non-Japanese Brazilians found an inverse association between isoflavone intake and breast cancer risk for Brazilians, whether Japanese or non-Japanese, but only a non-significant inverse association limited to postmenopausal women in Japan.
A German case-control study of premenopausal breast cancer found that the highest vs. lowest intake quartiles of dietary daidzein and genistein resulted in significantly reduced breast cancer risk. This protective effect was found to be associated with hormone receptor-positive tumors. High intake of other isoflavonoids such as formononetin and biochanin A, as well as total isoflavonoids, were not associated with a decrease in breast cancer risk. No impact on risk was found for total phytoestrogen intake. The authors concluded that the dietary intake of daidzein and genistein may have an important role in reducing breast cancer risk despite relatively low levels of intake.
A U.S. and Canadian case-control study designed to examine the associations between diet and premenopausal bilateral breast cancer found that total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake each were found to be inversely associated with risk of premenopausal bilateral breast cancer. On the other hand, intake of carbohydrates and sweetened beverages were associated with increased risk. Reductions in risk were also observed for intakes of low-fat dairy products and tofu. The authors concluded that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.
An Australian study that measured urinary isoflavones, as well as serum and urinary sex steroids in postmenopausal women with recently diagnosed breast cancer (before surgery) and disease-free controls found that the breast cancer cases had lower 24-hour urinary daidzein compared to controls and somewhat lower urinary genistein excretion. Total testosterone was found to be higher in women with breast cancer compared with controls. The authors commented that the findings were in keeping with other observational data demonstrating a protective effect from phytoestrogens on breast cancer risk.
A large Japanese prospective study found no significant associations between consumption of soy foods (tofu, boiled soybeans, miso soup) and the risk of breast cancer, including for postmenopausal women as a group. The authors concluded that consumption of soy food has no protective effects against breast cancer.
A Japanese case–control study found high intake of soybean products to be associated with lower risk of breast cancer in premenopausal women. The authors concluded that they had found a statistically significant inverse association between tofu or isoflavone intake and risk of breast cancer among premenopausal women but not among postmenopausal women.
A Chinese study of 5,042 breast cancer survivors found that soy food intake was inversely associated with breast cancer-related death and recurrence. Risks of recurrence and death both were found to be approximately 30% lower for women with the highest fourth of soy protein consumption compared to the lowest quartile. The results held for both estrogen receptor positive (ER+) and estrogen receptor negative (ER-) breast cancer.
A Chinese case-control study found that both premenopausal and postmenopausal women in the highest quartile of total isoflavone intake had reduced risks of all receptor status subtypes of breast cancer. A stronger protective effect of high isoflavone intake was found for breast cancer tumors with concordant rather than discordant receptor status; i.e., those with ER+/PR+ or ER-/PR- status.
A large prospective study of ethnically Chinese women in Singapore found that breast cancer risk was significantly reduced in association with high soy intake for postmenopausal women (but not for premenopausal women). The protective effect was stronger in women with above median body mass index than in leaner women.
A large Chinese prospective study designed to investigate the impact of soy intake on risk of breast cancer found an inverse dose-response relationship for the intake of all the individual soy food items evaluated in the study, including tofu, fresh soybeans, dried beans, soy products, soy bean sprouts, and soy milk. The inverse association was stronger among pre-menopausal women. When adolescent soy consumption was considered, pre-menopausal women with the highest soy protein intake during both adolescence and adulthood had a more than 50% lower risk compared to women with the lowest soy intake in both periods.
A Korean case-control study comparing the diets of breast cancer patients with a healthy control group found that the breast cancer patients consumed significantly fewer eggs and a significantly lower quantity of bean curd (tofu), onion, garlic, green pepper, sweet pepper, kale, cucumber, seasoned bean sprouts, sesame leaf, zucchini, radish, mushroom, crown daisy, red pepper paste, bean paste, spicy bean paste, orange juice, grape juice, and tomato juice than the controls. On the other hand, the breast cancer patients consumed significantly greater quantities of cooked rice, noodles, deep fried chicken, satsuma mandarin, Korean melon, kimchi and coffee than the controls.
Another Korean case-control study designed to examine the relationship between fruit, vegetable, and soy intake and the risk of breast cancer found that, in premenopausal women, high tomato consumption was associated with lower breast cancer risk. In postmenopausal women, high grape, green pepper, and soybean consumption were each found to be associated with lower breast cancer risk.

Tofu consumption, in particular, appears to be associated with reduced risk (see our tofu web page).

Additional comments

Soybeans should be avoided during radiation treatment because genistein has been shown to protect cells against cell death caused by radiation damage, raising the possibility that consuming soybeans will lessen the cytotoxic impact of radiation on breast cancer cells.

Edamame are immature soybeans, typically prepared by boiling them whole in their green pods. Tempeh is made by the controlled fermentation of cooked soybeans.

Soybeans have relatively high levels of phytic acid, which binds to some ingested minerals such as calcium, magnesium, iron, and zinc in the intestinal tract, and thereby reduces the amounts available in the body. This can be undesirable for people with a low intake of essential minerals (especially infants and young children).

Tags: Australian, Chinese, ER+, ER+/PR+, ER-, ER-/PR-, German, Japanese, Korean, PR-, beanCurd, calcium, chicken, coffee, daidzein, dairy, genistein, hotPeppers, insulinLikeGrowthFactor, iron, kale, kimchi, melon, mushrooms, onions, oranges, phytoestrogens, polyunsaturatedFat, radiationTreatment, radioprotective, sesame, soyProteinIsolate, soybeans, tofu, tomatoes

Selected studies

Soy Food Intake and Breast Cancer Survival Journal of the American Medical Association, December 2009

The present Chinese population study was designed to investigate the association between soy consumption and survival from breast cancer. Study participants included 5,042 women in the Shanghai Breast Cancer Survival Study aged 20 to 75 years and diagnosed during the period March 2002 to April 2006. The women were followed until June 2009. Personal interviews were undertaken approximately six months after diagnosis to collect participant information concerning cancer diagnosis and treatment, lifestyle factors (including diet) since cancer diagnosis, and disease progression. The information was reassessed at three follow-up interviews which took place at 18, 36, and 60 months. Linkage with the Shanghai Vital Statistics Registry database was used to obtain survival information for study participants lost to follow-up. In addition, medical records were reviewed to verify breast cancer diagnosis and treatment information. Cox regression analysis, with adjustment for known clinical predictors and other lifestyle factors, was used to estimate associations. Intake of soy food was treated as a time-dependent variable. During a median follow-up period of 3.9 years (range = 0.5 to 6.2 years), 444 deaths and 534 recurrences or breast cancer-related deaths occurred in the 5,033 survivors who had been surgically treated. Soy food intake, as measured by either soy protein or soy isoflavone intake, was found to be inversely associated with death and recurrence. The hazard ratio (HR) associated with the highest fourth of soy protein intake was 0.71 (95% confidence interval (CI) = 0.54 - 0.92) for total mortality and 0.68 (95% CI = 0.54 - 0.87) for recurrence compared to the lowest quartile of intake. Multivariate-adjusted four-year mortality was 10.3% and the recurrence rate was 11.2% for participants in the lowest quartile of soy protein consumption compared to 7.4% mortality and 8.0% recurrence for those in the highest quartiles of soy protein consumption. The inverse association was found among participants with both estrogen receptor positive (ER+) and estrogen receptor negative (ER-) tumors and among both users and nonusers of tamoxifen. The authors concluded that among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

Dietary isoflavone intake and breast cancer risk in case–control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians Breast Cancer Research and Treatment, July 2009

The present hospital-based case-control study was designed to investigate the association between isoflavone intake and breast cancer risk among Japanese, Japanese Brazilians and non-Japanese Brazilians. The study participants included a total of 850 matched pairs (390 Japanese, 81 Japanese Brazilians and 379 non-Japanese Brazilians) aged 20 to 74 years old. The cases had confirmed primary invasive breast cancer and were matched with controls from medical checkup examinees in Nagano, Japan and from cancer-free patients in São Paulo, Brazil. Study participants completed validated food frequency questionnaires. Odds ratios (ORs) were calculated using a conditional logistic regression model. A statistically significant inverse association between isoflavone intake and breast cancer risk was observed for Brazilians, whether Japanese or non-Japanese. In the case of Japanese women, a non-significant inverse association limited to postmenopausal women was found. In the three populations combined, breast cancer risk was found to decrease linearly from zero to moderate isoflavone intake levels and thereafter leveled off. Median isoflavone intake was divided into quintiles: 8.7, 23.1, 33.8, 45.7, and 71.3 mg/day. Compared to non-consumers, adjusted ORs (95% confidence interval) for consumers in increasing quintile intake categories were 0.69 (0.44–1.09), 0.54 (0.31–0.94), 0.45 (0.26–0.77), 0.34 (0.19–0.62), and 0.43 (0.24–0.76), respectively. The authors conclude that they found an overall inverse association between dietary isoflavone intake and risk of breast cancer and that their findings suggest a risk-reducing rather than risk-enhancing effect of isoflavones on breast cancer within the range achievable from dietary intake alone.

Childhood Soy Intake and Breast Cancer Risk in Asian American Women Cancer Epidemiology Biomarkers & Prevention, April 2009

The present population-based case-control study was designed to investigate the association between childhood soy intake and breast cancer risk in U.S. women of Asian descent. Breast cancer rates are substantially higher in the U.S. than in Asia. When Asian women migrate to the U.S., their breast cancer rates rise over several generations and finally approach that of U.S. Caucasians. One explanation is that modifiable factors such as diet may be important. The study included women aged 20-55 years of Chinese, Japanese, and Filipino descent, living in San Francisco-Oakland, Los Angeles or Oahu (Hawaii). The 597 breast cancer cases and 966 controls were interviewed about adolescent and adult diet and cultural practices. For participants with mothers living in the U.S. (39% of participants), 99 mothers of cases and 156 mothers of controls were interviewed about their daughter's childhood diets and exposures. Comparing the highest with the lowest thirds, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were found to be 0.40 (95% CI = 0.18 - 0.83; Ptrend = 0.03), 0.80 (0.59-1.08; 0.12), and 0.76 (0.56-1.02; 0.04), respectively. Inverse associations with childhood intake were found in all three groups, all three study sites, and women born both in Asia and the U.S. Adjustment for measures of westernization lowered the associations with adolescent and adult soy intake but did not change the inverse relationship with childhood soy intake. The authors conclude that soy may be a hormonally related, early-life exposure that influences breast cancer incidence.

Dietary intake of isoflavones and breast cancer risk by estrogen and progesterone receptor status Breast Cancer Research and Treatment, February 2009

The current Chinese case-control study was designed to examine the association between dietary isoflavone intake and breast cancer risk by estrogen receptor (ER) and progesterone receptor (PR) status. The study, which was conducted in southeast China during 2004–2005, included 756 incident breast cancer cases and 1,009 age-matched healthy controls recruited from outpatient breast clinics. Isoflavone intake was assessed using face-to-face interviews with a validated food-frequency questionnaire. Tumor ER and PR status was obtained from pathologic reports. Women in the highest quartile of total isoflavone intake were found to have reduced risks of all receptor status subtypes of breast cancer with a dose-response relationship compared to women in the lowest intake quartiles. The adjusted ORs (95% CIs) were 0.39 (CI = 0.27–0.58) for ER+, 0.32 (CI = 0.21–0.49) for ER−, 0.43 (CI = 0.29–0.64) for PR+, and 0.30 (CI = 0.19–0.45) for PR− (P for trend <0.001). These inverse associations persisted in both premenopausal and postmenopausal women after stratification. A stronger protective effect of high isoflavone intake was seen for breast cancer tumors with concordant rather than discordant receptor status; i.e., those with ER+/PR+ (OR 0.39, 0.26–0.59) or ER−/PR− (OR 0.28, 0.17–0.44) status. The authors comment that the finding that isoflavones protect against all tumor subtypes of breast cancer have biological plausibility since they are supported by evidence from experimental studies.

Soy intake and breast cancer risk in Singapore Chinese Health Study British Journal of Cancer, July 2008

The current prospective study investigated the effects of soy isoflavone intake on breast cancer risk in 35,303 Singapore Chinese women enrolled during the period April 1993 to December 1998 in the Singapore Chinese Health Study. Each subject was administered personally a validated semiquantitative food frequency questionnaire covering 165 food and beverage items at recruitment into the study. As of year-end 2005, 629 women had developed breast cancer. Using Cox regression analysis and adjusting for age at interview, year of interview, education, dialect group, family history of breast cancer, age when periods became regular, number of children, menopausal status, body mass index, omega-3 fatty acid intake, and other covariates, breast cancer risk was found to be significantly reduced in association with high soy intake. Relative to women with below median soy consumption (<10.6 mg isoflavone per 1000 Kcal), women with above median consumption had a significant 18% risk reduction (relative risk (RR) = 0.82, 95% confidence interval (CI) = 0.70–0.97). The inverse association was found in postmenopausal women (RR = 0.74, 95% CI = 0.61–0.90), but not in premenopausal women (RR = 1.04, 95% CI = 0.77–1. 40). Among postmenopausal women, the soy-breast cancer relation was stronger in those above median body mass index (RR=0.67, 95% CI=0.51–0.88) than in leaner women (RR=0.83, 95% CI=0.62–1.11). Duration of follow-up was also important: the protective effect of soy consumption was found to be twice as large among women with at least 10 years of follow up compared to those with fewer years of follow up. Neither estrogen nor progesterone receptor status of the tumors materially affected the association. The authors conclude that approximately 10 mg of isoflavones per day, obtainable in a standard serving of tofu, may have lasting beneficial effects against breast cancer development.

Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study Cancer Causes and Control, October 2007

The present Japanese population-based, prospective study was designed to evaluate the association between the incidence of breast cancer and soy food consumption. The authors analyzed data from the Japan Collaborative Cohort (JACC) Study. During the period 1988 - 1990, 30,454 women aged 40 to 79 years completed a questionnaire on diet and other lifestyle features. During a mean follow-up period of 7.6 years, 145 new cases of breast cancer were detected. No significant associations were found between the risk of breast cancer and consumption of tofu, boiled soybeans, and miso soup. The multivariate hazard ratios (HRs) (95% CI) in the highest category of consumption were 1.14 (CI = 0.74 - 1.77) for tofu, 0.77 (CI = 0.47-1.27) for boiled soybeans and 1.01 (CI = 0.65-1.56) for miso soup. Restricting the analysis to postmenopausal women, there were also no significant associations between soy foods and the risk of breast cancer. The authors conclude that consumption of soy food has no protective effects against breast cancer.

Comparisons of food intake between breast cancer patients and controls in Korean women Nutrition Research and Practice, September 2007

The current case-control study was designed to compare the diets of a group of Korean breast cancer patients with a healthy control group. The cases included 97 women with newly confirmed diagnoses of breast cancer at the inpatient or outpatient clinic of Yeouido St. Mary’s Hospital in Seoul, and excluded women with any history of liver diseases, diabetes mellitus, respiratory disorders and cardiovascular diseases. The 97-person control group also excluded women with known malignant, hormonal, gynecological or endocrine diseases. Intake of nutrients in 117 food items were estimated in the breast cancer patients and age-matched healthy controls using a quantitative food frequency questionnaire administered by a trained dietitian. The questionnaire also included general information (age, sex and marital status), age at menarche, and pregnancy history. It was found that the average caloric intake of the breast cancer patients and the healthy controls did not differ significantly. However, the breast cancer patients consumed significantly less fat and antioxidant nutrients such as vitamin A, retinol, beta-carotene, vitamin C and vitamin E than did the controls. Consumption of eggs (p<0.01), legumes (p<0.05), vegetables (p<0.05), seasonings (p<0.001), and oils and fats (p<0.01) was significantly lower in the breast cancer patients. However, the level of energy from fat is relatively low in Korean patients compared to their Western counterparts, and fat consumption may not be an independent risk factor at this level of intake. With respect to particular foods, in addition to eggs, the breast cancer patients consumed a significantly lower quantity of bean curd (tofu), onion, garlic, green pepper, sweet pepper, kale, cucumber, seasoned bean sprouts, sesame leaf, zucchini, radish, mushroom, crown daisy, red pepper paste, bean paste, spicy bean paste, orange juice, grape juice, and tomato juice than the controls. On the other hand, the breast cancer patients consumed significantly greater quantities of cooked rice, noodles, deep fried chicken, satsuma mandarin, Korean melon, kimchi and coffee than the controls. The authors conclude that since the breast cancer patients consumed less soy and vegetables, they had a lower intake than the controls of rich sources of antioxidant nutrients, phytosterols, fiber and non-nutritional components that may reduce the risk of cancer. In addition, the breast cancer patients in this study consumed lower quantities of red pepper paste, bean paste and spicy bean paste, causing their intake of pepper flavonols (which may have a protective effect on breast cancer risk) to be lower than that of the controls.

Fruits, vegetables, soy foods and breast cancer in pre- and postmenopausal Korean women: a case-control study International Journal for Vitamin and Nutrition Research, March 2007

The present Korean case-control study was designed to examine the relationship between fruit, vegetable, and soy intake and the risk of breast cancer. The study subjects consisted of 359 breast cancer cases and 708 hospital-based controls selected from the same hospitals. Usual dietary habits were determined using a semi-quantitative 98-item food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by unconditional logistic regression after adjusting for menopausal status. In premenopausal women, high tomato consumption was found to be associated with lower breast cancer risk (OR = 0.59, 95% CI = 0.38-0.89, p for trend = 0.04). In postmenopausal women, high grape consumption was found to be associated with lower breast cancer risk (OR = 0.59, 95% CI = 0.35-0.95; p for trend = 0.05), as was high green pepper consumption (OR = 0.60, 95% CI = 0.43-0.96, p for trend = 0.03) and high soybean intake (OR = 0.61, 95% CI = 0.34-0.89, p for trend = 0.02). The authors conclude that high intake of some fruits, vegetables, and soybeans may be associated with reduced breast cancer risk.

Serum Insulin-Like Growth Factor-I Levels Among Women in Hawaii and Japan With Different Levels of Tofu Intake Nutrition and Cancer, January 2006

The current cross-sectional study compared insulin-like growth factor-I (IGF-I) levels in Japanese women in Japan and Japanese and Caucasians in Hawaii with high and low soy intake. IGF-I is thought to be a link between diet and breast cancer risk since high circulating levels of IGF-I appears to increase cell proliferation and reduce apoptosis. Due to their estrogen-like structure, soy isoflavones could affect IGF-I levels similarly as exogenous estrogens. The study included 611 pre- and postmenopausal women who had participated in a previous study, but who were never diagnosed with breast cancer. The women underwent screening mammograms, provided blood samples, and completed validated food-frequency questionnaires. The same laboratory was used to analyze all serum samples for IGF-I and IGF binding protein (IGFBP)-3. Covariate-adjusted mean IGF-I and IGFBP-3 levels by tofu intake were calculated. The average IGF-I levels were 213 for Japanese in Japan, 257 for Japanese in Hawaii, and 255 ng/ml for Caucasians in Hawaii. Tofu intake was higher in Japan than among either Hawaiian groups. Average IGF-I levels were found to be 11% lower among women in the highest tofu consumption category compared with the lowest, but the difference in IGF-I levels between tofu consumption levels was only significant among women in Japan. The authors conclude that a diet rich in soy foods and low in meats may be related to lower IGF-I levels, but it is unclear whether soy or other characteristics of diet and lifestyle are responsible for this association.

Soy food intake and breast cancer risk: A report from the Shanghai Women's Health Study Proceedings of American Association for Cancer Research (AACR), Volume 47, 2006

The present Chinese prospective study was designed to investigate the impact of soy intake on risk of breast cancer. Soyfood is a rich source of isoflavones, a class of phytoestrogens with established anti-estrogenic and anti-carcinogenic effects. However, population studies examining the association between soy or soy isoflavone intake and risk of breast cancer have been inconclusive. The study included 73,311 women who participated in the Shanghai Women's Health Study. A validated food frequency questionnaire was employed to determine usual dietary intake at baseline and during follow-ups. After an average follow-up period of 5.7 years (415,534 person-years), 441 incident cases of breast cancer were identified. Total soy protein (p trend =0.004) and isoflavone (p trend =0.01) intake were both found to be associated with lower risk of breast cancer. An inverse dose-response relationship was also found for the intake of all the individual soy food items evaluated in the study, including tofu (p trend =0.02), fresh soybean (p trend<0.001), dried bean (p trend =0.002), soy products (p trend<0.001), soy bean sprout (p trend =0.07), and soy milk (p trend<0.001). The inverse association was found to be stronger among pre-menopausal women (p interaction = 0.01). When adolescent soy consumption was considered, pre-menopausal women with the highest soy protein intake during both adolescence and adulthood had a more than 50% lower risk (RR=0.47, 95% CI: 0.28-0.79) compared to women with the lowest soy intake in both periods. The authors conclude that this large population-based prospective study provides thus far the strongest evidence that soy consumption reduces the risk of breast cancer.

Soybean products and reduction of breast cancer risk: a case–control study in Japan British Journal of Cancer, June 2005

The current Japanese case–control study was designed to evaluate the association between soybean consumption and breast cancer risk. Elements of the Japanese diet that might contribute to the relatively low breast cancer rates in Japan have not been clarified in detail. The study focused on soybean products since they are widely consumed in Japan. Data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC) was used. A total of 167 breast cancer cases and 854 controls confirmed as cancer-free were included. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multiple logistic regression analysis. High intake of soybean products was found to be associated with lower risk of breast cancer in premenopausal women. Compared with women in the lowest third, the adjusted ORs for highest tertile intake of tofu was 0.49 (95% CI = 0.25–0.95). A significant reduction in risk of premenopausal breast cancer was also found for increasing consumption of isoflavones (OR=0.44; 95% CI = 0.22–0.89 for highest vs. lowest tertile; P for trend=0.02). The authors conclude that they found a statistically significant inverse association between tofu or isoflavone intake and risk of breast cancer among premenopausal women but not among postmenopausal women.

Soy processing influences growth of estrogen-dependent breast cancer tumors Carcinogenesis, May 2004

The current study was designed to investigate the ability of various soy products containing genistin (the glycoside form of genistein) to affect the growth of MCF-7 breast cancer cells transplanted into ovariectomized mice. Soybean-based products consumed in Asian countries are minimally processed whereas in the U.S. many soy foods and soy ingredients are highly processed. The soy products investigated included soy flour, two crude extracts of soy (soy molasses and Novasoy®), a mixture of isoflavones, and genistin in pure form. Each of the soy flour products was added to the mouse diet in a manner designed to provide equivalent amounts of genistein equivalents. Tumors in the negative control animal group regressed throughout the study while the tumors in the soy flour-fed animals remained basically the same size (neither grew nor regressed). However, in mice consuming soy molasses, Novasoy®, mixed isoflavones or genistin alone, tumor growth was found to be stimulated compared to animals consuming a control diet devoid of soy. These dietary treatments also resulted in increased cellular proliferation. In further testing, changes in mRNA expression of gene targets (estrogen responsiveness, cell cycle progression, apoptosis and aromatase activity) in tumors induced by the different diets were evaluated. The relative expression of pS2, progesterone receptor and cyclin D1 was higher in animals consuming the Novasoy®, mixed isoflavones and genistin. Bcl2 mRNA expression was low in most of the dietary treatment groups compared to positive (estradiol implant) controls. Aromatase expression was not altered in any of the treatment groups. The authors conclude that the degree of soy flour processing impacts the estrogenicity of products containing a constant amount of genistein. The findings suggest that for postmenopausal women with estrogen-dependent breast cancer, consumption of foods containing soy flour is more advisable than consuming isoflavones in more purified forms.

Dietary Phytoestrogen Intake and Premenopausal Breast Cancer Risk in a German Case-Control Study International Journal of Cancer, February 2004

The present German case-control study of breast cancer by age 50 was designed to evaluate the association between dietary intake of various phytoestrogens and premenopausal breast cancer risk. A diet high in isoflavonoids (soy) has been found to be associated with lower breast cancer risk in among Asians. However, since soy intake is relatively low in Western populations, dietary lignans may be the more important phytoestrogen class in these women. In the study, diet-related data was collected from 278 premenopausal breast cancer cases and 666 age-matched controls using a validated food frequency questionnaire. Using multivariate logistic regression, the highest vs. lowest intake quartiles of dietary daidzein and genistein intake resulted in significantly reduced odds ratios (ORs) (95% CI) for breast cancer risk of 0.62 (0.40–0.95) and 0.47 (0.29–0.74), respectively. The protective effects of daidzein and genistein were found to be associated with hormone receptor-positive tumors. High intake of other isoflavonoids such as formononetin and biochanin A, as well as total isoflavonoids, were not associated with a decrease in breast cancer risk. High intake of the plant lignan matairesinol was associated with significantly reduced breast cancer risk (OR = 0.58, 95% CI 0.37–0.94), but lower risk was not associated with consumption of the lignan secoisolariciresinol or with the sum of plant lignans. However, the estimated intake of both mammalian lignans, enterodiol and enterolactone, were found to be inversely associated with breast cancer risk (ORs = 0.61 (0.39–0.98) and 0.57 (0.35– 0.92), respectively). No impact on risk was found for total phytoestrogen intake. The authors conclude that the dietary intake of daidzein and genistein may have an important role in reducing breast cancer risk despite low levels of intake, and matairesinol and mammalian lignans may also reduce breast cancer risk.

Phytoestrogens and breast cancer in postmenopausal women: a case control study Menopause, September-October 2000

The present Australian study was designed to examine the associations between isoflavones, androgens, and dietary composition and breast cancer risk in postmenopausal women. The study included 18 women with recently diagnosed breast cancer (before surgery) and 20 controls. Both cases and controls were assessed for urinary isoflavones, serum and urinary sex steroids, and dietary intake. The breast cancer cases were found to have lower 24-hour urinary daidzein compared to controls and there was also an observed trend to lower urinary genistein excretion. Total testosterone was found to be higher in women with breast cancer compared with controls (cases: 1.3 (95% CI: 1.1 - 1.5) nmol/L; controls: 1.0 (95% CI: 0.8 - 1.11) nmol/L; p = 0.05). No significant differences between cases and controls were found for (1) serum free androgen index, dehydroepiandrosterone sulphate, sex hormone binding globulin, estradiol and progesterone; or (2) urinary androgen metabolites; or (3) dietary intake with regard to fat, carbohydrate, protein, or fiber consumption. The authors comment that the findings are in keeping with other observational data demonstrating a protective effect from phytoestrogens on breast cancer risk.