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nosurrender

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Breast Cancer Treatment Can Be Undermined By The Dietary Supplement Genistein

24 Sep 2008  

Women taking aromatase inhibitors to treat breast cancer or prevent its recurrence should think twice before also taking a soy-based dietary supplement, researchers report.

Genistein, a soy isoflavone that mimics the effects of estrogen in the body, can negate the effectiveness of aromatase inhibitors, which are designed to reduce the levels of estrogens that can promote tumor growth in some types of breast cancer.

The new study, which included researchers from the University of Illinois, Virginia Polytechnic and State University and the National Center for Toxicological Research, appears in the journal Carcinogenesis.

Aromatase inhibitors are a mainstay of breast cancer treatment in post-menopausal women. These drugs work by interfering with the enzyme aromatase, which catalyzes a crucial step in converting precursor molecules to estradiol, the main estrogen in the body.

About two-thirds of all cases of breast cancer diagnosed in the U.S. are estrogen dependent or estrogen sensitive, which means that the tumors grow more rapidly in the presence of estrogen.

Most women diagnosed with breast cancer are post-menopausal, so their ovaries are no longer producing normal levels of estrogen. Other tissues, however, produce a steroid hormone, androstenedione (AD), which - with the help of aromatases - is converted to testosterone and estrogens. The estrogens produced from AD can stimulate the growth of some types of breast cancer tumors.

The researchers conducted several trials in a mouse model of estrogen-dependent post-menopausal breast cancer. First, they gave the mice AD, which was converted to estrogen and created a high estrogen environment.

This helped the researchers determine the maximum growth rate of the breast cancer tumors.

Next, they added Letrozole, an aromatase inhibitor widely prescribed to post-menopausal women with estrogen-dependent breast cancer. This treatment (Letrozole) effectively blocked the effects of AD and the breast cancer tumors stopped growing.

But when they added genistein (a plant estrogen or "phytoestrogen" present in many dietary supplements) to the mix, the researchers observed a dose-dependent reduction in the effectiveness of the breast cancer drug. Specifically, the tumors began to grow again. They grew fastest at the highest dietary doses of genistein.

"To think that a dietary supplement could actually reverse the effects of a very effective drug is contrary to much of the perceived benefits of soy isoflavones, and unsettling," said William Helferich a professor of food science and human nutrition at Illinois and principal investigator on the study. "You have women who are taking these supplements to ameliorate post-menopausal symptoms and assuming that they are as safe as consuming a calcium pill or a B vitamin."

Many women take genistein supplements to control hot flashes and other symptoms of menopause. The researchers found that the doses commonly available in dietary supplements were potent enough to negate the effectiveness of aromatase inhibitors.

"These compounds have complex biological activities that are not fully understood," Helferich said. "Dietary supplements containing soy-based phytoestrogens provide high enough dosages that it could be a significant issue to breast cancer patients and survivors."

Plant estrogens from soy are not the only ones of concern, Helferich said. In a recent study, he and his colleagues found that certain mixtures of estrogenic botanical components and extracts marketed as supplements to assist "female libido enhancement" and sold without a prescription appeared to spur breast cancer tumor growth at low doses, while having no effect on tumors at high doses.

That study appeared last year in Food and Chemical Toxicology.

"We are just starting to understand the complex effects of the dietary supplements that contain phytoestrogens," Helferich said. "There is an ongoing human experiment in which the outcome is unknown. These findings raise serious concerns about the potential interaction of the estrogenic dietary supplements with current breast cancer therapies."

----------------------------
Article adapted by Medical News Today from original press release.

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Calico

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Reply with quote  #2 
Some supplements note soy as an ingredient. Would that be genistein or would genistein be noted as such?

I read labels pretty close, haven't seen genistein listed as such yet.

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Reply with quote  #3 
I am thinking it would be listed as Genistein... so all we have to do is be vigilant and avoid it!

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Reply with quote  #4 
I've always been confused by this. Is soy bad for all bc patients?

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Reply with quote  #5 
I was told that soy, in moderation, is fine for all of us.  Those of us who have er+/pr+ tumors should eat soy in moderation and avoid taking supplements with huge amounts of soy in them.  So you can take supplements that have soy in the capsule, have some tofu once in a while, but don't OD on soy milk or base your diet on tofu protein.

Hope that's right, Edge.


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edge

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Reply with quote  #6 

This study does not substantially change the conclusions of my critical review, the summaries of which I repeat below:

 

What the Evidence Says

At this time, the weight of the evidence from robust systematic reviews and meta-analyses favors either a modest benefit of long-term high soy consumption, especially from the genistein component, on reduction of breast cancer risk, or at worst - depending on many complex factors - no effect, and hence no deleterious effect; the evidence fails to support a significant component of harm on breast cancer risk.

 

In addition, there is some provisional evidence from Maria Hedelin's team at the Karolinska Institute that unlike isoflavones, flavones, and lignans, the coumestans within the class of flavonoids, may be of special benefit in breast cancer risk reduction in ER-negative disease, whereas the other phytoestrogens are largely relevant to ER-positive disease, although lignans may be of potential benefit across receptor status. The coumestans (with coumestrols as active components) include red clover sprouts and leaf, alfalfa and alfalfa sprouts, kudzu leaf, soybean sprouts, and mung bean sprouts. Note that coumestans are coumarin derivatives and hence structurally related to coumadin (Warfarin), so caution should be exercised in consuming other than small sporadic amounts if on antiplatelet / anticoagulant medication.

[from Phytoestrogens on this forum: 4/25/08]

 

Upon systematic review and critical appraisal, we find on the weight of the evidence that there is weak but not sufficiently dispositive data to support a modest protective effect of the standard American soy diet on breast cancer, with best guidance suggesting that the safest soy consumption is that of foods containing soy flour, in preference to more purified forms of isoflavones such as purified genistein, soy protein isolate, isoflavone-rich soy extracts, or isoflavone capsules, or soy that is ground, defatted and toasted, and that furthermore whole soybean products by virtue of their containing both the genistein and daidzein isoflavone components are unlikely to have any net-adverse impact on tamoxifen activity.

[from Breast Cancer Prevention Watch]

 

It should further be noted that this is a in vitro cell study using a breast cancer xenograft model and in this connection I critically note that no (stronger) in vivo study to date has ever demonstrated the in vivo induction of aromatase activity by genistein in actual  experimental animals (including non-experimental humans).  The researchers are also being disingenuous in saying that "You have women who are taking these supplements to ameliorate post-menopausal symptoms and assuming that they are as safe as consuming a calcium pill or a B vitamin": few women take such genistein supplements as described, since the supplements are not raw genistein, but a genistein + daidzein mixture, and as I have already observed, the combination is unlikely to exert pro-estrogenic activity.

 

Fancy's summary is excellent and right on target, and should be well heeded: consuming foods - not genistein supplements - with whole soybean or soy flour like soybeans themselves, soy foods including miso, tempeh, and tofu) should be unproblematic when kept below high (Asian) levels, which means under 20 to 80 grams of daily consumption.  Even considering the lower threshold, 20 grams daily, a cup of soy milk has just 30 mg. of genistein, and the highest amounts come from soybeans themselves, uncooked or roasted at just above 1 gram (1/2 cup).  In the typical Western diet it would therefore require an extraordinary amount of almost constant soy consumption, like 10 cups of soybeans daily or 666 cups of soy milk, to come close to this lower threshold, and in any case, all these products are whole soy and contain both genistein and daidzein.    

 


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com 

Calico

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Reply with quote  #7 
Thank you for explaining this again, Constantine.

While Tamoxifen works through estrogen receptors, soy seems okay.
I suppose some soy (in vitamin or supplement pills) has no adverse effect for us who take the AI's as well?. Somebody told me last week there is a difference (sitting on the confused couch again )



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Reply with quote  #8 

Calico:

 

No, it's a good question.  That's correct; soy in small clinically non-significant amounts is often an excipient (or filler) in many pills and drug formulations, being as we call it incidental in presence, but here the issue is large amounts of soy consumption primarily in the diet.  Therefore such incidental soy exposure is of no consequence (other than an occasional potential allergic reaction).

 


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com

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Reply with quote  #9 
Much appreciation and thank you again, Constantine, for taking the time to educate us.


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nosurrender

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Reply with quote  #10 
Thank you, Constantine.
I appreciate all this info but for myself, I am staying away from soy. I eat the ground flaxseeds and that is as close as I will go. Maybe when I feel safer now being ER+ I will try more dietary soy- but I am not there yet!



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coco

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Reply with quote  #11 
I am so grateful for this discussion as I am currently grappling with the Soy/No-Soy question myself.

I can't tolerate Tamoxifen due to severe cognitive impairment (I mean, I am one degree from drooling on this drug!). My Onc had me stop and is testing my estrogen levels to see where I'm at, presumably with the possibility of putting me on an AI.

A well-known writer and lecturer on women's breast health, whom I met recently, suggested I take a breast formula supplement which includes (among other things) a small amount of soy, plus the herbal supplement "Brevail" as an alternative to Tamoxifen. My previous Onc (I'm sort of in-between) said "no" to soy, so the thought of taking even a little makes me (like you, Gina) uneasy.

At first I thought this soy debate was primarily a traditional vs. holistic medicine thing, but it seems to me there is a considerable lack of consensus within the traditional medical field alone. As a patient, this is crazy-making!

I wonder if any of you have gone the supplement route versus Tamoxifen or AI's? I am so weary of all the SE's that I feel compelled to explore all the options.

Forgive me if I don't seem to be absorbing all of the helpful info offered here; I've spent an awful lot of time in parking lots lately, looking for my car...

Best to all.

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nosurrender

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Reply with quote  #12 
I know what you mean about looking for your car! LOL

I never heard about the Brevail.

Maybe we can get Constantine to weigh in on this- it is a good question!


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edge

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Reply with quote  #13 
Coco:

[Response repeated in another thread]

Brevail is a proprietary extract of (North American) flaxseed (Linum usitatissimum) with the lignan known as SDG (secoisolariciresinol diglucoside), along with several other ingredients (Vitamin D3 (400 IU), pinoresinol diglycoside, caffeic acid, ferulic acid and coumaric acid).  Although the manufacturer (Lignan Research) claims that "flaxseed lignan SDG exerts effects similar to the anti-estrogen drug tamoxifen with an apparently much greater degree of tolerability", there is no reliable human clinical evidence to support this, and the scientific validation cited by the company is constituted by preclinical in vitro and in vivo studies of SDG (and not of Brevail itself), and the preclinical evidence is insufficient to support efficacy in humans and in the special class of women with breast cancer. 
 
And although lignans are generally thought to be safe, data on anti-tumor efficacy is not wholly consistent (the just published large Swedish cohort study from Maria Hedelin at Karolisnska and her colleagues examined the activity of isoflavonoids, lignans, and coumestrol, and found no association between intake of isoflavonoids or lignans and breast cancer risk), although there is still a non-dispositive weighting of the balance of the evidence on the side of some potential modest benefit.  But even if there were some benefit of lignans and SDG in breast cancer risk reduction, there is no evidence of clinical efficacy of Brevail in the treatment of active breast carcinoma and claims that "flaxseed lignan SDG exerts effects similar to the anti-estrogen drug tamoxifen" lack scientific support in the clinic, so Brevail cannot be in any way construed as a substitute for tamoxifen, and any suggestion to the contrary, as hinted at in the manufacturer's literature, is reckless. 


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com

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Reply with quote  #14 
Thank you, Edge, for steering me clear. Your expertise is invaluable.


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nosurrender

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Reply with quote  #15 
Golly days! I guess I am on Brevail!
I eat flaxseed, vitamin d,  and caffeine!




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