Phytoestrogens – Harmful Or Beneficial For Hormone Driven Breast Cancer?

The subject of phytoestrogens and their role in hormone driven breast cancer comes up at least once per week (and usually WAY more than that) amongst breast cancer patients and survivors, and it can be an incredibly confusing subject. In an effort to untangle the confusion, I decided to share with you what I have discovered on the subject over the past few years.

What Exactly Is A Phytoestrogen?

The word phytoestrogen means “plant estrogen”.  Phytoestrogens are a group of chemicals found in plants that can act like the human hormone estrogen because their chemical structure is quite similar.

Phytoestrogens are found in these foods – soybeans, soynuts, soy milk, edamame, tempeh, tofu, miso, soy sauce, tamari, flaxseed (a/k/a linseed), sesame seeds, sunflower seeds, oats, barley, rye, hops (so yes, that includes beer), wheat germ, chickpeas, lentils, yams, alfalfa, apples, carrots, pomegranates, licorice root, red clover (and this is not an exhaustive list).

Here’s the Controversy

Many doctors and nutritionists will warn you against anything containing phytoestrogens, the argument being that phytoestrogens may increase the amount of estrogen in your body, and if you have hormone-driven cancer, this would be something better avoided.

With reference to red clover in particular, I came across a few websites that warned against phytoestrogens for those with breast cancer.  The American Cancer Society states on their website “Women who have had estrogen receptor-positive cancers or who are pregnant or breastfeeding should not use this herb.”   The National Center for Complementary and Alternative Medicine stated on their website: “It is unclear whether red clover is safe for women who are pregnant or breastfeeding, or who have breast cancer or other hormone-sensitive cancers.”  The webMD website stated: “Red clover might act like estrogen. If you have any condition that might be made worse by exposure to estrogen, don’t use red clover.”

These same warnings appear with relation to other phytoestrogens as well – soy and flaxseed, in particular. 

Phytoestrogens have to be one of the most misunderstood plant compounds on the planet.

The Holistic View

Natural therapists have been using phytoestrogens for their patients with hormone-driven cancers for several decades. Successfully, I might add, relying upon the anecdotal evidence of the patients that were successfully treated with them. For many years, we just had to know what we knew – that phytoestrogens were beneficial and protective – and wait for the research to back that up. We now have that research and I share that with you, below.

Here’s How Phytoestrogens Really Work

Phytoestrogens, once consumed, enter the body and dock with cells that have estrogen receptor sites on them. There are two kinds of estrogen receptor, alpha and beta. ER-alpha is known to promote proliferation (rapid growth) of breast cells. ER-beta opposes that action. According to studies, phytoestrogens have a higher affinity for docking with ER-beta.

Once docked, a phytoestrogen is able to either act similar to the body’s own estrogen, or it can act as an estrogen antagonist (meaning it opposes the action of the body’s own estrogen). 

This means that phytoestrogens are Selective Estrogen Receptor Modulators (or SERMs). An example of a well known SERM is the drug Tamoxifen, used for ER+ breast cancer, and indeed the chemical structure of phytoestrogens is similar to that of Tamoxifen.

Here’s the important part – when a phytoestrogen docks with an estrogen receptor on a cell, it exerts a MUCH WEAKER action than the body’s own estrogen. [1]

Whether a phytoestrogen acts as an estrogen or an antiestrogen seems to depend on the amount of circulating estrogen already in that person, as well as the number and type of estrogen receptors their cells display.

Other Expert Opinions on Phytoestrogens

Professor Trevor Powles, an authority on breast cancer and former head of the Breast Unit at The Royal Marsden Hospital in Surrey, UK, refers to phytoestrogens as “anti-estrogens”, because of how they block the action of human estrogen in the cancer process.  Professor Powles believes that phytoestrogens have the ability both to block the receptor sites to which human estrogens attach, and also in some cases to even denature more aggressive human estrogen.

Another reliable source of information is The Block Center for Integrative Oncology. In their article Soy And Breast Cancer [2], it is stated: “Women who eat more foods containing soy after their diagnosis have better survival overall than those who eat less soy. This conclusion was welcome, and may come as a bit of a surprise to some people, given all the negative press about phytoestrogens in soy (the Block Center staff have been aware of this trend in the research for a few years now). The conclusion is based on studies that found that women had better survival when they ate diets that are rich in soy foods, as well as diets that are rich in isoflavones. The phytoestrogen components of soy have chemical structures that are called isoflavones. The main sources of isoflavones in our diet are soy foods (though some processed soy foods might not have high isoflavone contents, and are likely to contain GMOs, which should be avoided). Other beans also contain isoflavones as well. We thus recommend soy foods and a variety of other beans as a regular part of your diet. What we don’t recommend – if you are a breast cancer survivor – are isoflavone supplements. These may have stronger estrogenic effects than soy foods, which may compromise their safety. We also don’t recommend making soy the main protein source of your diet, or drinking 7 glasses a day of soymilk, which one oddly designed study recently found had estrogenic effects on the breast.”

The Research on Phytoestrogens

Here are the studies I found most helpful.

A 2009 study [3] reported results based on 5,042 women diagnosed with breast cancer (these women were participating in the Shanghai Breast Cancer Survival Study) over a four-year period. The study found that women who regularly consumed soy products such as soy milk, edamame or tofu had a 32% lower risk of their breast cancer returning and a 29% decreased risk of death, compared with women who consumed little or no soy.

Flaxseed and its lignans have been much studied for their beneficial effects for those with breast cancer. A systematic review of studies reported in 2014 [4] found that just 25 grams of flaxseed (about 4 tablespoons of ground) decreased hot flashes, improved breast density, and had anti-cancer activity, offered a decreased risk of primary breast cancer, better mental health, and lower mortality among breast cancer patients. Flaxseed also significantly slowed down the rate of cells multiplying in the breast tissue of people who were at a higher risk for breast cancer, decreased the risk of breast cancer and reduced mortality risk among those living with breast cancer.

Another 2014 study [5] found that flaxseed reduced tumor growth in breast cancer patients, and that flaxseed lignans reduced the risk of breast cancer in premenopausal women. The authors stated that flaxseed and its components are effective in the risk reduction and treatment of breast cancer and safe for consumption by breast cancer patients.

A 2013 systematic review investigated soy and red clover [6] for their efficacy in improving menopausal symptoms in women with breast cancer, and for any potential impact on risk of breast cancer incidence or recurrence. The study authors concluded “Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors.”

Phytoestrogens May Benefit Triple Negative Breast Cancer Patients 

According to one 2015 cell study [7], those with triple negative breast cancer may benefit from phytoestrogens as well. In this in vitro (test tube) study, when phytoestrogens were added to the more aggressive and invasive triple negative human breast cancer cell line, researchers noticed a decrease in cell proliferation (rapid growth). A 2018 cell study [8] had similar findings. While cell studies certainly don’t replicate what happens in the body, this research bears watching.

Phytoestrogens for those on Anastrazole

The authors of a 2010 study [9] reported in the Canadian Medical Association Journal stated “There is growing evidence that soy isoflavones may have a protective effect in terms of initiation or progression of breast cancer because they inhibit the local production of estrogens.” In this study, the researchers found that there was a benefit in soy food intake for women taking the aromatase inhibitor anastrazole. Study authors stated “In the study reported here, high intake of soy isoflavones reduced the risk of recurrence among patients receiving anastrozole treatment. This effect might be due to the synergistic inhibitory effects of isoflavones and anastrozole on the synthesis of estrogen.”

Phytoestrogens for those on Tamoxifen

A 2004 animal study [10] examined the effects of flaxseed and tamoxifen – alone and in combination –  for  mice with estrogen receptor positive breast cancer.  Researchers found that the combination of flax and tamoxifen inhibited tumor size more than 53%, as compared with tamoxifen action alone. I read several such animal studies, all of which indicated that the combination of flax and tamoxifen worked better than either on its own at inhibiting breast cancer tumor size, growth and spread. Researchers don’t yet know if these results will apply to actual humans with breast cancer, but this approach — adding flaxseed to the diet — certainly looks promising. 

But There’s Always An Exception…or Two

For women with HER2+ tumors, a very small 2015 study [11], found that eating soy was associated with an increased rate of recurrence. Keep in mind that this study only included 339 women – 25 of whom had a breast cancer recurrence, and only eight of the 25 had HER2+ tumors. Based on this study and other research, there is insufficient evidence that HER2+ patients should avoid soy — this is simply something to be aware of. For women who had HER2- tumors, soy consumption was significantly protective, safe, and showed mostly positive effects. 

Please also be aware that flaxseed, another phytoestrogen, DECREASES HER2 over-expression [4]. Flaxseed has also been shown to increase the effectiveness of Herceptin, a targeted drug given to those with HER2+ breast cancer. [12] So flaxseed appears to be beneficial for those with HER2+ breast cancer.

The other group that might not benefit from soy is premenopausal women deemed to be at high risk for breast cancer. A very small 2012 clinical study [13] found that for this category of women, taking soy isoflavones appeared to increase the growth of breast cells. To be fair, the study did not use whole soy foods – instead they were using more concentrated components from soy – genistein, 150 mg, daidzein 74 mg, and glycitein 11 mg. One wonders if they would have found the same results had they been using whole soy foods.

Men also do not benefit from phytoestrogens – they appear to have lower sperm counts when they eat lots of foods containing phytoestrogens.

One Last Thing – Avoid Soy Protein Isolate

Since highly processed and concentrated phytoestrogens appear to have different effects on breast tumor cells, it is best to avoid highly processed soy, especially soy protein isolate, a known breast cancer risk. This is sometimes found in protein powders and other foods.

I recommend that people limit or avoid intake of concentrated supplements containing isoflavones like genistein, in favor of less-processed options such as the foods appearing in the list above. And please always choose organic soy, when you eat soy, and here’s why. Back in the late 90’s, only 8% of soy was genetically modified. As of 2015, 93% of the soy in the US was genetically modified — and you definitely don’t want that in your body.

Updated 2/27/2020

References:

[1] Selective Estrogen Receptor Modulators and Phytoestrogens: New Therapies for the Postmenopausal Woman – https://www.mayoclinicproceedings.org/article/S0025-6196(11)64138-4/fulltext

[2] Soy and Breast Cancer – https://lifeovercancer.wordpress.com/2014/10/17/soy-and-breast-cancer/

[3] Soy food intake and breast cancer survival – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874068/

[4] Flax and Breast Cancer: A Systematic Review – https://www.ncbi.nlm.nih.gov/pubmed/24013641

[5] Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer? – https://www.ncbi.nlm.nih.gov/pubmed/24869971

[6] Soy, red clover, and isoflavones and breast cancer: a systematic review – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842968/

[7] Inhibitory effects of enterolactone on growth and metastasis in human breast cancer – https://www.ncbi.nlm.nih.gov/pubmed/26473769

[8] Synergistic Effect of Bioactive Anticarcinogens from Soybean on Anti-Proliferative Activity in MDA-MB-231 and MCF-7 Human Breast Cancer Cells In Vitro – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099725/

[9] Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy–https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988534/

[10] Dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen-dependent human breast cancer (mcf-7) in nude mice – https://www.ncbi.nlm.nih.gov/pubmed/15570004/

[11] Differential influence of dietary soy intake on the risk of breast cancer recurrence related to HER2 status – https://www.ncbi.nlm.nih.gov/pubmed/22211813

[12] Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer — https://www.ncbi.nlm.nih.gov/pubmed/24869971

[13] Soy Isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3333836/

A Review of the Evidence for the Use of Phytoestrogens as a Replacement for Traditional Estrogen Replacement Therapy – https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/648139

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