How to Block Breast Cancer’s Estrogen-Producing Enzymes

The vast majority of breast cancers start out “hormone-dependent,” meaning the primary human estrogen, called “estradiol plays a crucial role in [breast cancer] development and progression.” That’s one of the reasons why soy food consumption appears so protective against breast cancer—because soy phytoestrogens, like genistein, act as estrogen-blockers. They block the binding of estrogens, like estradiol, to breast cancer cells.

But, wait a second. “The majority of breast cancers occur [after menopause], when the ovaries have [stopped producing estrogen].” What’s the point of eating estrogen blockers if there’s no estrogen to block? It turns out the breast cancer tumors themselves produce their own estrogen from scratch to fuel their own growth.

Estrogens may be formed in breast tumors by multiple pathways. The breast cancer takes cholesterol, and, using the aromatase enzyme, or two hydroxysteroid dehydrogenase enzymes, produces its own estrogen.

So, there’s two ways to stop breast cancer. One is to use “antiestrogens,” estrogen-blockers, like the soy phytoestrogens, or “the anti-estrogen [drug] tamoxifen…However, another way to block estradiol is by using anti-enzymes” to prevent the breast cancer from making all the estrogen in the first place.

And, indeed, there are a variety of anti-aromatase drugs in current use. In fact, inhibiting the estrogen production has been shown to be “more effective” than just trying to block the effects of the estrogen—”suggesting that the inhibition of estrogen synthesis is clinically very important for the treatment of estrogen-dependent breast cancer.” It turns out soy phytoestrogens can do both.

Using ovary cells taken from women undergoing in vitro fertilization, soy phytoestrogens were found to reduce the expression of the aromatase enzyme. What about in breast cancer cells, though? Breast cancer cells, too—not only suppressing aromatase activity, but the other estrogen-producing enzyme, too.

But, this is in a petri dish. Does soy suppress estrogen production in people too Well, circulating estrogen levels appear significantly lower in Japanese women than American white women. And, Japan does have the highest per capita soy food consumption. But, you don’t know it’s the soy until you put it to the test. Japanese women were randomized to add soymilk to their diet—or not—for a few months. Estrogen levels did seem to drop about a quarter in the soymilk-supplemented group. Interestingly, when they tried the same experiment in men, they got similar results: a significant drop in female hormone levels, with no change in testosterone levels.

These results, though, are in Japanese men and women that were already consuming soy in their baseline diet. So, it’s really just looking at “higher versus lower…soy intake.”

What happens if you give soymilk to women in Texas? Circulating estrogen levels cut in half. Since increased estrogen levels are a “[marker] for high risk for breast cancer,” the effectiveness of soy to reduce estrogen levels may help explain why Chinese and Japanese women have such low rates of breast cancer.

And, what was truly remarkable is that estrogen levels stayed down a month or two, even after they stopped drinking it. This suggests you don’t have to consume soy every day to have the cancer-protective benefit.

Doctor’s Note

Wait, soy protects against breast cancer? Yes, in study after study after study. Even in women at high risk? See BRCA Breast Cancer Genes & Soy.

Even if you already have breast cancer? See Is Soy Healthy for Breast Cancer Survivors?

Even GMO soy? See GMO Soy & Breast Cancer.

Okay, then, Who Shouldn’t Eat Soy? Watch that video too! 🙂

What else can we do to decrease breast cancer risk? See:

If you haven’t yet, you can subscribe to my videos for free by clicking here.

In health,
Michael Greger, M.D.

Michael Greger, M.D., is a physician, New York Times bestselling author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous “meat defamation” trial. Currently Dr. Greger proudly serves as the Director of Public Health and Animal Agriculture at the Humane Society of the United

Should Women at High Risk for Breast Cancer Avoid Soy?

Five studies have been performed on breast cancer survival and soy foods, involving more than 10,000 breast cancer patients. And, those who eat more soy live longer, and have a lower risk of the cancer coming back. But, what about women who carry breast cancer genes? Fewer than 10% of breast cancer cases run in families. But, when they do, it’s most likely mutations to one of the tumor suppressor genes—BRCA1 or BRCA2—that defend the integrity of our genes. They are involved in DNA repair, and so, if either one of them is damaged, or has mutations, chromosomal abnormalities can result, which can set us up for cancer.

This idea that we have tumor suppressor genes goes back to famous research in the 60s that showed that if you fuse together a normal cell with a cancer cell, the cancer cell doesn’t turn the normal cell malignant. Rather, the normal cell suppresses the cancerous one. Tumor suppressor genes are typically split up into two types. There are gatekeeper genes that keep cancer cells in check, and caretaker genes that keep the cell from going cancerous in the first place. And, BRCA genes appear able to do both—that’s why their function is so important.

breast-cancer-and-soy-concernsUntil recently, dietary recommendations for those with mutations focused on reducing DNA damage caused by free radicals, by eating lots of antioxidant-packed fruits and vegetables. If your DNA-repair capacity is low, you want to be extra careful about damaging your DNA in the first place. But, what if we could also boost BRCA function?

In my last video on the topic, I showed how, in vitro, soy phytoestrogens could turn back on BRCA protection suppressed by breast cancer, upregulating BRCA expression as much as 1,000% within 48 hours. But, does that translate out of the petri dish and into the person? Apparently so.

Soy intake was only associated with 27% breast cancer risk reduction in people with normal BRCA genes, but a 73% risk reduction in carriers of BRCA gene mutations. So, a healthy diet may be particularly important in those at high genetic risk. Meat consumption, for example, was linked to twice as much risk in those with BRCA mutations—97% increased risk, instead of just 41% increased risk of breast cancer in those with normal BRCA genes.

Doctor’s Note

What about for women without breast cancer genes, or for women who have already been diagnosed? That was the subject of my last video, Is Soy Healthy for Breast Cancer Survivors?. The older video I referred to is BRCA Breast Cancer Genes & Soy.

What is in meat that may increase risk? See, for example:

Featured Image From Authority Nutrition and Livestrong.

In health,

Michael Greger, M.D.

Michael Greger, M.D., is a physician, New York Times bestselling author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous “meat defamation” trial. Currently Dr. Greger proudly serves as the Director of Public Health and Animal Agriculture at the Humane Society of the United

Is Soy Healthy for Breast Cancer Survivors?

is-soy-healthy-for-breast-cancer-survivorsSoyfoods have become controversial in recent years,…even among health professionals,…exacerbated by misinformation found on the Internet.” Chief among the misconceptions is that soy foods promote breast cancer, because they contain a class of  phytoestrogen compounds called isoflavones. Since estrogens can promote breast cancer growth, it’s natural to assume phytoestrogens might too.

But, people don’t realize there are two types of estrogen receptors in the body—alpha and beta. And, unlike actual estrogen, soy phytoestrogens “preferentially bind to and activate [estrogen receptor beta]. This distinction is important, because the 2 [types of receptors] have different tissue distributions…and often function differently, and sometimes in opposite ways.” And, this appears to be the case in the breast, where beta activation has an anti-estrogenic effect, inhibiting the growth-promoting effects of actual estrogen—something we’ve known for more than ten years. There’s no excuse anymore.

The effects of estradiol, the primary human estrogen, on breast cells are completely opposite to those of soy phytoestrogens, which have antiproliferative effects on breast cancer cells, even at the low concentrations one gets in one’s bloodstream eating just a few servings of soy—which makes sense, given that after eating a cup of soybeans, the levels in our blood cause significant beta receptor activation.

So, where did this outdated notion that soy could increase breast cancer risk come from? The concern was “based largely on research that showed that [the main soy phytoestrogen] genistein stimulates the growth of mammary tumors in [a type of] mouse.” But, it turns out, we’re not actually mice. We metabolize soy isoflavones very differently from rodents. The same soy leads to 20 to 150 times higher levels in the bloodstream of rodents. The breast cancer mouse in question was 58 times higher. So, if you ate 58 cups of soybeans a day, you could get some significant alpha activation, too. But, thankfully, we’re not hairless athymic ovariectomized mice, and we don’t tend to eat 58 cups of soybeans a day.

At just a few servings of soy a day, with the excess beta activation, we would assume soy would actively help prevent breast cancer. And, indeed, “[s]oy intake during childhood, adolescence, and adult life were each associated with a decreased risk of breast cancer.” Those women who ate the most soy in their youth appear to grow up to have less than half the risk.

This may help explain why breast cancer rates are so much higher here than in Asia—yet, when Asians come over to the U.S. to start eating and living like Americans, their risk shoots right up.  For example, women in Connecticut—way at the top of the breast cancer risk heap—in their fifties have, like, ten times more breast cancer than women in their fifties living in Japan. But, it’s not just genetic, since when they move here, their breast cancer rates go up generation after generation, as they assimilate into our culture.

Are the anti-estrogenic effects of soy foods enough to actually change the course of the disease? We didn’t know, until the first human study on soy food intake and breast cancer survival was published in 2009 in the Journal of the American Medical Association, suggesting that “[a]mong women with breast cancer, soy food consumption was significantly associated with decreased risk of death and [breast cancer] recurrence.” Followed by another study, and then another, all with similar findings.

That was enough for the American Cancer Society, who brought together a wide range of cancer experts to offer nutrition guidelines for cancer survivors, to conclude that, if anything, soy foods should be beneficial. Since then, two additional studies have been published, for a total of five, and they all point in the same direction. Five out of five, tracking more than 10,000 breast cancer patients.

Pooling all the results, soy food intake after breast cancer diagnosis was associated with reduced mortality (meaning a longer lifespan) and reduced recurrence—so, less likely the cancer comes back. Anyone who says otherwise hasn’t cracked a journal open in seven years.

And, this improved survival was for both women with estrogen receptor negative tumors and estrogen receptor positive tumors, and for both younger women, and for older women. Pass the edamame.

Doctor’s Note

This is probably the same reason flax seeds are so protective. See Flax Seeds & Breast Cancer Survival: Epidemiological Evidence and Flax Seeds & Breast Cancer Survival: Clinical Evidence.

What about women who carry breast cancer genes? I touched on that in BRCA Breast Cancer Genes & Soy, and it’s the topic of my next video, Should Women at High Risk for Breast Cancer Avoid Soy?

What about genetically modified soy? I made a video abut that too; see GMO Soy & Breast Cancer.

Who Shouldn’t Eat Soy? Glad you asked. Watch that video too! 🙂

Not all phytoestrogens may be protective, though. See The Most Potent Phytoestrogen is in Beer and What are the Effects of the Hops Phytoestrogen in Beer?

In health,

Michael Greger, M.D.

Michael Greger M.D.Michael Greger, M.D., is a physician, New York Times bestselling author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous “meat defamation” trial. Currently Dr. Greger proudly serves as the Director of Public Health and Animal Agriculture at the Humane Society of the United

GMO Soy and Breast Cancer

GMO Soy And Breast CancerBy: Dr. Michael Greger, Director of Public Health and Animal Agriculture at the Humane Society of the United States.

In response to concerns raised about the toxicity of Monsanto’s roundup pesticide, which ends up in GMO foods, Monsanto’s scientists countered that these in vitro experiments used physiological irrelevant concentrations, meaning dripping roundup on cells in a petri dish at levels far above what would be realistically found in the human body.

Sure, it’s probably not a good idea to mix up your alcohol with your roundup and chug the stuff, or try to commit suicide by drinking it, or injecting it into you. And the rare cases of Parkinson’s reported were after getting directly sprayed with the stuff, or working for years in a pesticide production plant, but that’s not your typical consumer exposure.

Some of the researchers responded to the accusation saying look, we used the kinds of concentrations that are used out in the fields. Therefore every little droplet you spray worldwide is above the threshold concentration we found caused adverse effects. Monsanto’s folks responded saying yes, that’s the concentration we spray, but that’s not the concentration that human cells are bathing in. Once it gets into drinking water or food, it’s highly diluted. And, they’re quick to point out, if you look at people with the greatest exposure—pesticide workers—the vast majority of studies show no link between the use of roundup and cancer or non-cancer diseases. There are a few suggestive findings suggesting a link with non-Hodgkins lymphoma. One study of pesticide applicators suggested an association with multiple myeloma, and one study of the children of pesticide applicators found a tentative association with ADHD, but again these are folks expected to a much greater exposure level the general population that may just get a few parts per million in their food. But there had never been any studies done on the tiny levels found circulating in people’s bodies, until now.

The maximum residue levels are set at parts per million. The concentrations found within human bodies is measured in parts per billion. This study found glyphosate can activate estrogen receptors at a few parts per trillion, increasing the growth of estrogen receptor positive human breast cancer cells in a petri dish. These results indicate that truly relevant concentrations of the pesticide found on GMO soybeans possesses estrogenic activity.

But consumption soy is associated with lower breast cancer risk, and improved breast cancer survival.

That may be because most GMO soy in the U.S. is fed to chickens, pigs, and cows—it’s used for livestock feed, whereas most of the major soy food manufacturers use non-GMO soy. Or it could be because the benefits of eating any kind of soy may far outweigh the risks, but why accept any risk at all when you can organic soy products, which by law exclude GMOs.

The bottomline is that there is no direct human data suggesting harm from eating GMOs, though in fairness such studies haven’t been done, which is exactly the point, critics counter. That’s why we need mandatory labeling on GMO products so that public health researchers can track whether GMOs are having any adverse effects.

It is important to put the GMO issue in perspective though. As I’ve shown, there are dietary and lifestyle changes we can make that could eliminate most heart disease, strokes, diabetes, and cancer. Millions of lives could be saved. A healthy enough diet can even reverse our #1 killer, heart disease. So I’m sympathetic to the biotech industry’s exasperation about GMO concerns when we still have people dropping dead from everything else they’re eating. As one review concluded “Consumption of genetically modified food entails risk of undesirable effects… similar to the consumption of traditional food. In other words, buying the non-GMO Twinkie isn’t doing our body much of a favor.

Michael Greger M.D.About Michael Greger M.D.
Michael Greger, M.D., is a physician, author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous “meat defamation” trial. Currently Dr. Greger proudly serves as the Director of Public Health and Animal Agriculture at the Humane Society of the United States.

Doctor’s Note

This is the final installment of a 4-part videos series on the latest science on the public health implications of genetically engineered crops in our food supply. Check out the first three here:

For more on soy and breast cancer, see Breast Cancer Survival and Soy and BRCA Breast Cancer Genes and Soy.

To put the GMO issue in perspective in terms of the death and disability resulting from the standard American diet, see Lifestyle Medicine: Treating the Causes of Disease and my live presentations Uprooting the Leading Causes of Death and From Table to Able: Combating Disabling Diseases with Food.

If you haven’t yet, you can subscribe to my videos for free by clicking here.

BRCA Breast Cancer Genes and Soy

BRCA Breast Cancer Genes and SoyBy: Dr. Michael Greger, Director of Public Health and Animal Agriculture at the Humane Society of the United States.

Why do people who eat legumes—beans, chickpeas, split peas, and lentils live longer? Well, men and women who eat legumes tend to be lighter, have a slimmer waist, lower blood pressure, lower blood sugars, lower cholesterol, lower triglycerides, better kidney function and so no surprise may live longer, but, interestingly, bean intake was a better protectant against mortality in women than men. They think this may be because cancer was the leading killer of women in this population, especially breast cancer. And we know that breast cancer survivors who eat soy foods, for example, have a significantly lower likelihood of the cancer recurrence, eating soy foods appears to protect against the cancer coming back. This 2012 review looked at the three prospective human studies done to date and found that women who ate the most soy had a 29% lower risk of dying from breast cancer and a 36% lower risk of cancer recurrence. And a fourth study was since published, and it showed the same thing. Soy food intake is associated with longer survival and lower recurrence among breast cancer patients. With an average intake of soy phytonutrients above 17 mg/day, which is about what’s found in a cup of soymilk, the mortality of breast cancer may be able to be reduced by as much as 38%.

Here’s the survival curve over five years… The purple line represents the survival of the women with the highest soy consumption. As you can see, after 2 years all of the breast cancer survivors eating lots of soy were still alive, but a quarter to a third of the women who ate the least soy were dead. And after 5 years 90% of the tofu lovers were still alive and kicking, where as half of the tofu haters kicked, the bucket. And you see a similar relationship when you look at breast cancer survival and soy protein intake, as opposed to the phytonutrient intake.

How does soy so dramatically decrease cancer risk and improve survival? Soy may actually help turn back on BRCA genes. BRCA is a so-called caretaker gene, an oncosuppressor, meaning a cancer-suppressing gene responsible for DNA repair. Mutations in this gene can cause a rare form of hereditary breast cancer, popularized by Angelina Jolie’s public decision to undergo a preventive double mastectomy, but only about 5% of breast cancers run in families. So 95% of breast cancer victims have fully functional BRCA genes, so if their DNA repair mechanisms are intact, how did breast cancer form, grow, and spread? It does it by suppressing the expression of the gene through a process called methylation. The gene’s fine, but cancer found a way to turn it off, or at least turn it down, potentially facilitating the metastatic spread of the tumor.

And that’s where soy may come in. Maybe the reason soy intake is associated with increased survival and decreased cancer recurrence is because the phytonutrients in soy turn back on your BRCA protection, removing the methyl straightjacket the tumor tried to place on it, so researchers put it to the test. These are three different types of human breast cancer, specially stained so that the expression of BRCA genes shows up brown. So this is what full DNA repair would look like, hopefully what normal breast cells would look like. Lots of brown, lots of BRCA expression, but instead we have column 2, raging breast cancer. Well if you add soy phytonutrients to the cancer, BRCA gets turned back on, the DNA repair appears to start ramping back up. Though this was at a pretty hefty dose, equivalent to about a cup of soybeans, their results suggest that treatment with soy phytonutrients might reverse DNA hypermethylation and restore the expression of the tumor suppressor genes BRCA1 and BRCA2. May help with other breast cancer genes as well. Women at increased genetic risk of breast cancer may especially benefit from high soy intake.

Michael Greger M.D.About Michael Greger M.D.
Michael Greger, M.D., is a physician, author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous “meat defamation” trial. Currently Dr. Greger proudly serves as the Director of Public Health and Animal Agriculture at the Humane Society of the United States.

Doctor’s Note

Legumes leading to a longer life? See my last video, Increased Lifespan From Beans.

No matter what genes we inherit, changes in diet can affect DNA expression at a genetic level. For examples see:

I’ve previously covered the available science in Breast Cancer Survival and Soy. Other effects detailed in:

It may be possible to overdo it, though (How Much Soy Is Too Much?).

For more context check out my blogs: Top 10 Most Popular Videos from 2013 and Can Eating Soy Prevent Breast Cancer?

If you haven’t yet, you can subscribe to my videos for free by clicking here.

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