Effects Of Isoflavones On Mammary/breast Cell Proliferation
Animal studies
Concern over the possible tumor-stimulatory effects of isoflavones is based largely on the proliferative effect of genistein on MCF-7 cells in vitro and in studies of mammary cancer in rodents. A variety of studies have shown that isoflavones stimulate ER+ human breast cancer cell xenoplants in ovariectomized athymic mice , estrogen-dependent mammary tumors in rats , and reproductive tissues in adult female mice . Other research using rodent models has also demonstrated that genistein is the primary isoflavone responsible for tumor stimulation that more processed soy products result in faster tumor growth than less processed soy products and that genistein inhibits the efficacy of tamoxifen, a SERM used in the treatment and prevention of breast cancer .
Even in rodent models, however, isoflavones are generally weak estrogen agonists relative to E2. Most rodent studies use scaled doses at least 5 times the amount found in traditional Asian diets , and many studies have used direct injection of purified isoflavones, which results in substantially higher levels of unconjugated isoflavones than dietary administration . Importantly, the isoflavone dose required for estrogen-like effects in women has yet to be identified despite three decades of study. So although isoflavones clearly act as estrogens in rodent models, relevant dose effects for human consumption are still very unclear.
Clinical studies
If You Have Breast Cancer
In 2017 , the Breast Cancer Family Registry followed the intake of soy isoflavones for 6,235 women diagnosed with breast cancer and living in the U.S. and Canada. It was found that women who ate the highest amounts of soy isoflavones had a 21 percent lower risk of death compared with women with the lowest intakes.
What Human Studies Show
A number of long-term studies involving human populations have shown that eating soy foods does not increase the risk of breast cancer. On the contrary: Studies show that diets rich in soy may actually help to protect you from developing breast cancer.
A 2020 study that tracked the soy consumption of over 300,000 women in China found that moderate soy consumption did not raise the risk of breast cancer for women in the study. Women in the study who reported eating higher amounts of soy products experienced a lower risk of breast cancer.
A 2020 meta-analysis evaluated the results of 18 separate studies. After evaluating the results of these studies, researchers concluded that higher amounts of soy in the diet lowered the breast cancer risk for women. The protective effect was highest for women who had not yet reached menopause.
American Cancer Society say soy foods are safe and healthy for people to eat. They caution, however, that more research needs to be done to see whether taking isoflavone supplements is equally safe, since these supplements may have higher concentrations of isoflavones than there are in soy foods.
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The Questions About Soy And Breast Cancer
Before launching into the controversy about soy and breast cancer, it’s important to point out that this is about more than one question. Many of you have heard that soy may lower the risk of breast cancer, but that breast cancer cells grown in a dish grow more rapidly if fed soy. What is that all about? Some of the separate questions include:
- Can soy intake lower the risk of developing breast cancer? If so, is there a window of time in which it may accomplish this, or does the effect last throughout life?
- Is it safe for those with breast cancer to eat soy, or will it make breast cancer grow faster or increase recurrence?
- Are soy supplements safe for those at risk of breast cancer or who already have breast cancer?
- How may soy interact with the medications commonly used to treat breast cancer?
Phytoestrogens And Soy: The Debate
Phytoestrogens are compounds that have a mild estrogenic effect and are found in whole grains, nuts and seeds, and many other botanicals, fruits and vegetables. These foods are associated with a reduced risk of breast cancer as well as reduced cancer reoccurrence.
The controversy becomes heated in the debate over soy-containing foods. This issue is complex, with some studies showing that eating soy early in life can reduce breast cancer risk. On the other hand, the consumption of concentrated soy extracts showed increased proliferation of breast cancer cells. Finally, other studies show a protective or neutral effect from whole soy foods.
My recommendation for soy is to eat whole soy foods in moderation no more than several servings per week, preferably fermented soy foods such as miso or tempeh. Avoid soy protein isolates and supplements containing concentrated soy isoflavones.
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The Same Cannot Be Said For Soy Supplements
If you have estrogen-receptor positive cancer, DO NOT USE SOY SUPPLEMENTS.
But.Don’t skip WHOLE SOY FOODS and miss out on all the AMAZING CANCER-FIGHTING BENEFITS OF SOY FOODS.
ONE WORD OF CAUTION:
No one food or one nutrient, including soy foods, can greatly reduce your risk of cancer. Simply adding soy foods to a typical American diet that is high in fat and low in fiber is NOT a good idea. Remember, there is a lot of research evidence that shows that our total ‘pattern’ of diet is far more important than any one food or nutrient in our diet.
The pattern that most fights cancer?? Focus on getting the majority of your calories from whole plant foods such as fruits, vegetables, legumes , and WHOLE grains. We know that all Americans should eat a minimum of 5 servings of fruits and vegetables daily, yet most only get one or two servings.
If you’ve had cancer or are at high risk of cancer, you should aim for at least 8 to 10 servings of fruits and vegetables daily. Most people think, “oh, that’s crazy, I could never eat that.” But you have to remember that a serving isn’t one per each time you sit down to eat. You might get 2 to 3 servings in a single sitting, especially if you base your meals and snacks around plant foods.
Many researchers and health experts believe that the majority of the cancer fighting benefits of soy foods are not related to estrogen properties of soy foods.
Continue learning about soy, tofu and other vegetarian options
Lets Set The Record Straight: Phytoestrogen And Estrogen Are Not The Same
So, where does the idea come from that soy can increase your risk for breast cancer? Much of the confusion surrounding soy comes from a component of the legume called isoflavones. Isoflavones are compounds found in plants. The compounds have a similar chemical structure to human estrogen. For this reason, isoflavones are also known as phytoestrogens.
Many people confuse human estrogen with phytoestrogen, but they are not the same thing. Phytoestrogens behave differently than estrogen in the body and may help prevent cancer, heart disease and inflammation.
Soy phytoestrogens are much weaker than human estrogen. While more research is needed, human population studies show regular inclusion of soy is not harmful and may actually be helpful in preventing breast cancer, says Groeger.
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Is Soy Safe For Cancer Patients
Stephanie Meyers, MS, RD/LDNSenior Nutritionist Dana Farber Cancer Institute
What should I do about soy? is a common question among cancer survivors. On one hand, consuming soy foods like edamame, tofu and unsweetened soy milk have been shown to reduce the risk of certain cancers such as breast cancer, prostate cancer and gastric cancer. On the other hand, questions about the potential estrogenic activity of soy can lead to confusion about the safety of eating soy foods, particularly for those with hormone sensitive cancers, such as estrogen-receptor positive breast cancer.
Soy contains compounds called phytoestrogens. It is important to realize that when people eat soy it does not turn into estrogen in the body. Phytoestrogens, specifically genistein and daidzein, are structurally different and significantly weaker than human estrogen. No one food, soy included, is capable of single-handedly disrupting hormones linked to cancer growth. Nonetheless, non-evidence based sources make claims about soy that can create unnecessary fear amongst cancer patients. Lets take a closer look at the scientific research to date.
When deciding about inclusion of soy in your diet, it can be helpful to think about three distinct categories of soy products:
Soy As Part Of A Plant
A typical Western diet including red or processed meats, refined grains, sweets, alcohol, and high-fat dairy products, all which have been associated with increased cancer risk and higher rates of obesity, a cancer risk in its own right. On the other hand, plant-based diets include a higher intake of vegetables, fruits, whole grains, fish, poultry, and low-fat dairy products and have been shown to cancer risk.
Soy has an important place in our diets, particularly in regard to the plant-based diet that many are choosing to embrace in an effort to transition away from consuming animal products in light of the wide range of benefits that the plant-based diet has shown to provide.
Soy is a versatile food staple that spans across a variety of food categories. Nutritionally, it contains whole food carbohydrate and lean protein, as well as a healthful fat profile. It also provides a hearty source of calcium when fortified.
When including soy, it is recommended to choose whole food, organic when possible, sources of soy such as tofu, tempeh, edamame, soy nuts, and soymilk. Supplements should be avoided as they have not been studied sufficiently. In fact, preliminary studies have shown that supplements do not offer the same protective benefit of whole food soy products.
Soy Photo courtesy of
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Limit Salt And Sodium
Eating foods with a lot of salt can raise your blood pressure and increase your risk for stroke, heart failure, and kidney disease. Most people should eat less than 2,300 mg of sodium per day. Fresh food that isnt processed is usually lower in sodium.
Read food labels to find out the amount of sodium in the product. Choose foods that are labeled low sodium, very low sodium, or sodium-free.
Follow these tips to reduce how much sodium you eat:
- When cooking, flavor your foods with fresh herbs and spices instead of salt.
- Limit the amount of canned foods you eat .
- Limit the amount of packaged, processed, pickled, and cured foods you eat .
- Dont add salt to your food at the table.
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Are Soy And Flaxseeds Ok
Soy contains phytoestrogens, or plant-based estrogens, which has raised concerns regarding soy’s role in the development of breast cancer however, whole soy products, such as tofu, edamame or soy milk, have been shown to reduce the risk of breast cancer, including ER-positive cancers. This plant protein is also considered a healthy choice for breast cancer survivors.
In fact, a 2010 study from JAMA of more than 5,000 women living in China linked regular, whole soy intake to a reduced recurrence of all breast cancer types. However, isolated soy â found in supplements, soy powder or processed foods â should not be emphasized, as these foods have not been shown to be protective.
Flaxseeds are rich in lignans, a phytoestrogen, and also a good source of omega-3 fats and dietary fiber. Animal studies have shown that components of flaxseed can reduce tumor size and inhibit the growth of ER-positive and ER-negative breast cancer cells and that foods that contain lignan, such as flaxseed, may help decrease breast cancer risk, according to the American Institute for Cancer Research.
Although incorporating small amounts of flaxseed into a healthy diet is encouraged, inadequate human research is available to recommend large amounts of flaxseed, or flaxseed supplements, as a therapy for breast cancer.
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Clinical Research Involving Markers Of Breast Cancer Risk
TABLE 1
Effects of Soy Isoflavone Exposure on Mammographic Density
Numerous studies have evaluated the effects of isoflavone exposure on markers of breast cancer risk, including reproductive hormone levels, mammographic density, nipple aspirate fluid contents, and cell proliferation . Agents that raise breast cancer risk, eg, combined hormone therapy, increase mammographic density and cell proliferation, whereas agents that lower risk, such as tamoxifen, decrease these markers. As discussed below, the totality of evidence indicates that regardless of the source, isoflavone exposure does not adversely affect breast tissue.
TABLE 2
Description of Studies Evaluating Effects of Soy Isoflavone Exposure on Breast Cell Proliferation
Reproductive hormones
In the 11 studies involving premenopausal women in the meta-analysis, soy or isoflavone consumption did not affect primary outcomes-estradiol, estrone, or SHBG concentrations, but it significantly reduced secondary outcomes-FSH and LH , and menstrual cycle length was increased by 1.05 days . The authors were unable to conclude whether the changes in FSH and LH reflect an estrogenic or antiestrogenic effect, and another group of investigators has noted that longer menstrual cycles are associated with a reduced breast cancer risk.
Mammographic density
Nipple aspirate fluid
Breast cell proliferation
TABLE 3
Description of Epidemiologic Studies Evaluating the Effects of Soy Intake on Breast Cancer Prognosis
Soy Phytoestrogens & Estrogen
So if soy is such a health food, why the concern about estrogen and breast cancer risk? The answer lies in how certain types of breast cancer operate. While there are several types of breast cancer, the most common cancer is ER-positive, or estrogen-receptor positive cancer, meaning that the amount of estrogenA female sex hormone that is primarily produced by the ovaries. Its primary function is to regulate the menstrual cycle and assist in the production of secondary sex characteristics such as breasts. It may even play a role in the production of cancer cells in the breast tissue. in the body will effect the growth rate of that cancer. Effective treatments for these types of cancers often involve limiting estrogen in the body to limit the spread and growth of the cancer.
Phytoestrogen, also called dietary estrogen, is a naturally occurring plant-derived compound that chemically looks a bit like estrogen. Phytoestrogens can be found in a large variety of common plant-based foods like soy, flaxseed, sesame seeds, oats, barley, beans, lentils, apples and carrotsvirtually the Whos Who of healthy foods. Yet up until very recently, the fear of researchers was that phytoestrogen would act similarly to estrogen in the body and help ER-positive breast cancers to grow.
The simple fact is that while similar, phytoestrogens are not estrogen and to date, studies have not shown that phytoestrogens increase breast cancer risk, mortality or recurrence.
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Does Soy Lower The Risk Of Breast Cancer
Although there are not enough data to know whether soy may help protect against breast cancer, many studies suggest that it does.3-4 However, it seems the benefit only comes with a pattern of intake that is seen in most Asian countries, where women begin eating soy early life and eat it in amounts many times greater than typically seen in the U.S.4 In Japan, for example, soy intake ranges from 25 mg to around 50 mg per day. In the U.S., intake ranges from less than 1 mg to 3 mg per day.5
Results from an analysis that combined findings from multiple studies in Asian populations found that women who ate high amounts of soy had a 25 percent lower risk of breast cancer compared to those who ate lower amounts.6 When the same analyses were done in studies of U.S. and other Western populations, there was no link between soy and breast cancer risk.6
Is Soy Safe For Patients With Breast Cancer
When it comes to eating soy foods, there are a lot of myths about whats safe for cancer survivors and patients in cancer treatment.
As a breast cancer survivor and senior clinical dietitian at MD Anderson, Christie Siebel is passionate about debunking misinformation so patients get the nutrients they need to stay healthy.
Siebel shares this advice for patients and survivors who seek to avoid soy.
Soy foods are safe for patients with cancer
Siebel stresses that soy is generally safe to eat. Soy is a great alternative to animal protein to include in your daily diet, she says. Theres no reason to avoid eating soy.
Soy contains phytoestrogens the plant form of hormone estrogen. Because the names sound similar, Siebel says there has been hesitation around eating phytoestrogen, especially among patients with breast cancer and other types of cancer that are hormone-sensitive.
For many breast cancer patients, treatment involves blocking estrogen to prevent cancer cells from forming.
Though they sound similar, these hormones arent the same, and eating phytoestrogens doesnt affect the estrogen found naturally in your body.
Soy foods may reduce your risk of cancer
Research suggests eating soy foods may reduce risk of cancer recurrence even in patients with estrogen receptor-positive cancer. Soy isnt bad for you, and it may actually be beneficial for cancer prevention, Siebel says.
Thats why I try to eat soy every day, says Siebel, who carries the BRCA gene.
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Hormonal Receptor Status And Endocrine Therapy
We stratified the analyses for risk of recurrence according to estrogen and progesterone receptor status and endocrine therapy for postmenopausal patients. Statistically significant inverse associations between intake of soy isoflavones and recurrence were observed for patients with estrogren- and progesterone-positive disease and for patients receiving anastrozole therapy . Among postmenopausal patients with estrogren-and progesterone-positive breast cancer, those in the highest quartile of isoflavone intake had a significantly lower risk of recurrence than those in the lowest intake quartile . The recurrence rate of estrogren-and progesterone-positive breast cancer was 12.9% lower among patients in the highest quartile of soy isoflavone intake than among those in the lowest quartile. Among postmenopausal patients receiving anastrozole therapy, those in the highest quartile of isoflavone intake had a significantly lower risk of recurrence than those in the lowest intake quartile . The recurrence rate for post-menopausal patients receiving anastrozole therapy was 18.7% lower among patients in the highest quartile of soy isoflavone intake than those in the lowest quartile.