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The Cancer Research

Soy foods contain several key nutrients and phytochemicals studied for their cancer prevention properties. Many soy foods also contain dietary fiber, which links to lower risk of colorectal cancer. Soy foods contain isoflavones, which are phytoestrogens that in some ways mimic the action of estrogen. Because high levels of estrogen link to increased breast cancer risk, there was a fear that soy foods – and its isoflavones – may increase risk. Yet overall, human studies show soy foods do not increase risk and in some cases, research suggests they may lower it.

Current Evidence: AICR/WCRF Expert Report and its Continuous Updates (CUP)

Soybeans, soy nuts and edamame contain fiber. After a systematic review of the global scientific literature, AICR/WCRF weighed the strength of the evidence linking these factors to lower risk for cancer development. This comprehensive review concluded:

- There is strong – probable – evidence that foods containing dietary fiber DECREASE the risk of colorectal cancer.

Source: AICR/WCRF. Diet, Nutrition, Physical Activity and Cancer: A Global Perspective, 2018..

”These findings are great news for women who want to use soy as a source of protein while cutting back on animal protein, such as red and processed meat, for better health and lower cancer risk.”
Bette J. Caan, DrPH

Open Areas of Investigation: Laboratory Research

The majority of laboratory research involving soy and cancer risk has involved soy’s isoflavones genistein and daidzein.

In cell and animal studies, genistein, daidzein and other soy compounds have slowed cancer cell growth and prevented tumor formation. In lab studies, soy and genistein have decreased tumor growth and increase self-destruction of prostate cancer. Soy and its phytochemicals appear to prevent cancer development by reducing inflammation, and inhibiting activation of proteins that promote cell growth.

Some early studies in rodents suggested that genistein increased growth of estrogen receptor-positive (ER+) breast cancer cells, and it promoted breast cancer growth.

Studies show that rats and mice metabolize phytoestrogens such as genistein differently than humans (and other non-human primates). For soy and its components, the relevance of animal studies to humans remains unclear. Rodent metabolism leads to much higher levels of the active form of isoflavones compared to humans. Therefore, many researchers now say that the effects on breast cancer growth seen in rodent studies may be linked to their far higher blood levels of isoflavones in active form, and would not be expected to occur in humans.

Also, recent cell research shows that soy isoflavones such as genistein are much more likely to bind to a particular type of estrogen receptor in humans called ER-beta, rather than to ER-alpha. When activated, ER-alpha receptors appear to promote cell growth.10 Emerging evidence suggests ER-beta receptors act as a potential tumor suppressor that inhibits cell growth. ER-beta receptors are found in the breast and other tissues throughout the body. In some tissues, such as bone, ER-beta receptors may stimulate healthful non-reproductive effects.

Open Areas of Investigation: Human Studies

In general, Americans do not eat large amounts of soy, which makes it challenging for US observational studies to compare how highest versus lowest intake links to cancer risk. The majority of population studies involving soy are conducted in Asia, where soy is a dietary staple. Even so, across populations, studies now point to soy possibly protecting against some cancers and overall, presenting no increased risk.

Population studies link soy consumption with lower breast cancer risk in Asia, where women consume moderate amounts of soy throughout their life. A moderate amount is approximately one to two servings a day. Research now suggests that hormone-related protective effect of soy against breast cancer relates to soy consumption in childhood, adolescence, and throughout puberty. Soy also may affect cancer risk in some populations more than others, due to differences in genetics and gut bacteria that metabolize soy compounds into their active form.

AICR/WCRF’s latest continous update report on breast cancer (2010) said the evidence is suggestive, but too inconsistent to conclude that soy reduces risk of breast cancer. Beyond breast cancer, AICR/WCRF’s 2007 expert report concluded there was only limited evidence linking soy or total isoflavone consumption to lower risk of cancers of the prostate and stomach. A handful of studies link soy or total isoflavone consumption with lower risk of lung and colon cancers.

Clinical Trials: Among women without cancer, several randomized controlled trials have studied consuming soy protein powder or soy isoflavone supplements for six months to two years. One study focused on breast cancer patients; see below 'What about cancer survivors.' The amounts of isoflavones consumed in the studies are equal to or higher than what Asian women typically eat – one to two servings a day.

Overall, the studies among cancer-free women show no difference between the women who consume or do not consume isoflavones in hormone levels or breast density, a marker of increased breast cancer risk.

There is some research that suggests how a woman metabolizes isoflavones may play a role in lowering breast cancer risk. About a quarter of the US population has gut bacteria that metabolizes soy isoflavones into a compound called equol. In one clinical trial, for example, women who metabolized isoflavones into equol after eating soy appeared to benefit more than women who do not produce much equol. In the equol-producing women, eating soy shifted the body’s production of estrogen to more favor another form of the hormone. Lab studies suggest that this other form does not promote breast cancer growth, but research on this is ongoing.

This also fits with limited population studies suggesting that part of why people differ in the benefits they get from soy involves how much equol they produce when they consume it.

What about cancer survivors?

Breast Cancer Survivors: Overall, the seven recent epidemiologic studies examining soy consumption among breast cancer survivors – in six population studies and one combined analyis – show that consuming moderate amounts of soy foods does not increase a woman’s risk for poorer outcomes. The amounts classified as moderate are comparable to what Asian women consume. Some of the studies point to a potential benefit among women receiving certain treatments or with certain tumor characteristics.

Among Asians, postmenopausal women who ate the most soy foods – about two to three servings a day –had the lowest risk of recurrence or death compared to women who ate the least, less than a few serving a week. These findings were also seen in studies among predominantly Caucasian women who consumed soy at levels comparable to the average Asian.

In the largest study to date, a pooled analysis of studies that included almost 10,000 breast cancer patients, consuming at least 10 milligrams isoflavones (mg) daily linked to a 25 percent decrease in breast cancer recurrence. This effect was seen among both women from the United States and Asia, and was most evident in survivors of ER-negative cancer and those with ER-positive cancer taking tamoxifen.

For soy supplements, one 2014 randomized controlled trial studied the effects of soy powder protein among women diagnosed with breast cancer, before their surgery. The study showed that soy supplementation alters the expression of genes associated with promoting breast cancer. With consumption only lasting from 7 to 30 days and many unknowns about other gene changes, the  clinical significance of the study is unclear. Amounts of isoflavones consumed were above those recognized as safe – which is 100 mg/day – underscoring the point that more is not necessarily better. Studies supporting benefits of a moderate level should not be used to support use of much higher amounts of a nutrient or compound.

Overall, these population studies do not show any harmful interactions between soy foods and anti-estrogen medications. A small number of studies even suggest soy foods may be most protective for women who take tamoxifen or an aromatase inhibitor, but more research is needed.

What Is A Moderate Amount?

Moderate consumption is 1 to 2 standard servings daily of whole soy foods, such as tofu, soy milk, edamame and soy nuts. (One serving averages about 7 grams of protein and 25 mg isoflavones.) Studies have demonstrated up to 3 servings/day – up to 100 mg/day of isoflavones – consumed in Asian populations long-term does not link to increased breast cancer risk.

Prostate Cancer Survivors: Increasing levels of prostate-specific antigens (PSA) may indicate signs of prostate cancer development. Overall, trials have hinted that soy foods may lower PSA levels and may benefit prostate cancer survivors; none of the studies have demonstrated harm.

In several clinical trials of men with various stages of prostate cancer who were experiencing increases in PSA, the rate of PSA rise tended to slow in those consuming soy milk or isolated soy isoflavones. The isoflavone intake among these men ranged from 30 to 200 mg of isoflavones daily for six to 12 months. This intake correlated from the typical amount to double that of the typical Asian diet. This effect was stronger in some men than others, and it was not clear whether genetics and/or differences in metabolism explain these findings.

One trial using higher dosage of isoflavones showed no effect on PSA levels. And in another clinical trial, a soy protein containing isoflavones was not effective at decreasing the inflammatory or metabolic changes in prostate cancer survivors due to androgen deprivation treatment. However, 200 mg of isoflavone supplements daily during radiation therapy for prostate cancer decreased side effects of treatment, including decreased sexual function, leaky bladder and diarrhea.

Thanks to our expert reviewers:

Bette J. Caan, DrPH, Senior Research Scientist, Kaiser Permanente
Suzanne Dixon, MPH, MS, RD, The Health Geek, LLC
Mark Messina, PhD, MS, Nutrition Matters, Inc.

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