No need to avoid soy - new research

[Jackie07]

Here's a new report on soy consumption:

Cancer Epidemiol Biomarkers Prev. 2011 Feb 25. [Epub ahead of print]
Soy Food Consumption and Breast Cancer Prognosis.

Caan BJ, Natarajan L, Parker BA, Gold EB, Thomson CA, Newman VA, Rock CL, Pu M, Al-Delaimy WK, Pierce JP.
1Division of Research, Kaiser Permanente.
Abstract

BACKGROUND: Contrary to earlier clinical studies suggesting soy may promote breast tumor growth, two recent studies demonstrate that soy-containing foods are not adversely related to breast cancer prognosis. Using data from the Women's Healthy Eating and Living (WHEL) study, we examined the effect of soy intake on breast cancer prognosis.
METHODS: 3088 breast cancer survivors, diagnosed between 1991 and 2000 with early stage breast cancer and participating in WHEL were followed for a median of 7.3 years. Isoflavone intakes were measured post-diagnosis using a food frequency questionnaire (FFQ). Women self-reported new outcome events semi-annually which were then verified by medical records and/or death certificates. Hazard ratios (HR) and 95% confidence intervals (CI) representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates using the delayed entry Cox proportional hazards model.
RESULTS: As isoflavone intake increased, risk of death decreased (p for trend=0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) - had a non-significant 54% reduction in risk of death.
CONCLUSIONS: Our study is the third epidemiological study to report no adverse effects of soy foods on breast cancer prognosis. Impact: These studies, taken together, which vary in ethnic composition (two from the US and one from China) and by level and type of soy consumption, provide the necessary epidemiological evidence that clinicians no longer need to advise against soy consumption for women diagnosed with breast cancer.

[ElaineM]

Oh Thank you Jackie !!!!!!!!!
See the other post about tomatoes, carrots and soy and you will understand why I am so thankful for your post. Smile.

[radiant]

Well, this really gives Dr. Block even more street cred. He told me last year soy is fine. ;-)

- Kim

[ElaineM]

Cheers for Dr. Block. It sounds like he is aware of the current research about diet and cancer. I attended one of his teleconferences a couple years ago. It was very interesting.

[Jackie07]

Two articles:

Soy Foods Not A Risk For Breast Cancer Survivors
http://www.medicalnewstoday.com/articles/221451.php

Talking Soy: Safe For Women, Breast Cancer, In General?

http://www.medicalnewstoday.com/articles/221522.php

which provide more detailed description on the research, were posted in the 'Breast Cancer Newsfeed' on April 6.

[sdstarfish]

Interesting, I went to the Alternative/Complementary Cancer Therapies conference in March, and there was a Dr. there stressing that non-GMO, fermented soy is good for breast cancer survivors. Trouble is, the U.S. has so much of the junky soy products. So I could see where this could create a load of confusion.
Lisa
www.pinkkitchen.info

[Jackie07]

Didn't find one about breast cancer, but this abstract warned about Gastric cancer. However, I wondered if the pickled food that's been consumed by both the Japanese and the Korean people play an more important role.

Cancer Sci. 2011 Jan;102(1):231-44. doi: 10.1111/j.1349-7006.2010.01770.x. Epub 2010 Nov 10.
Fermented and non-fermented soy food consumption and gastric cancer in Japanese and Korean populations: a meta-analysis of observational studies.

Kim J, Kang M, Lee JS, Inoue M, Sasazuki S, Tsugane S.
Cancer Epidemiology Branch, Research Institute, National Cancer Center, Goyang, Korea. jskim@ncc.re.kr
Abstract

Soy food is known to contribute greatly to a reduction in the risk of gastric cancer (GC). However, both Japanese and Korean populations have high incidence rates of GC despite the consumption of a wide variety of soy foods. One primary reason is that they consume fermented rather than non-fermented soy foods. In order to assess the varying effects of fermented and non-fermented soy intake on GC risk in these populations, we conducted a meta-analysis of published reports. Twenty studies assessing the effect of the consumption of fermented soy food on GC risk were included, and 17 studies assessing the effect of the consumption of non-fermented soy food on GC risk were included. We found that a high intake of fermented soy foods was significantly associated with an increased risk of GC (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.02-1.44, I(2) = 71.48), whereas an increased intake of non-fermented soy foods was significantly associated with a decreased risk of GC (overall summary OR = 0.64, 95% CI = 0.54-0.77, I(2) = 64.27). These findings show that a high level of consumption of non-fermented soy foods, rather than fermented soy foods, is important in reducing GC risk.

[Jackie07]

Lymphat Res Biol. 2010 Mar;8(1):89-98.
The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products.

Barnes S.
Department of Pharmacology & Toxicology, University of Alabama at Birmingham and Purdue University - University of Alabama at Birmingham Botanicals Center for Age-Related Disease, Birmingham, Alabama 35294, USA. sbarnes@uab.edu
Abstract

In this review of the chemistry, absorption, metabolism, and mechanisms of action of plant isoflavones, emphasis is placed on the isoflavones in soy and the food products derived from them. Soybeans have been part of food history in Asia for several millennia but did not reach the Americas and Europe until the eighteenth century. In the twentieth century, there was a tremendous increase in the cultivation of soybeans in the United States and more recently in South America. Soy foods have entered the U.S. food supply in ever-increasing amounts both in the form of traditional products (soy milk, tofu) and in more subtle ways in dairy and bread/cake products. The isoflavones in non-fermented foods are for the most part in the form of glycoside conjugates. These undergo changes due to different processing procedures. Isoflavones and their metabolites are well absorbed and undergo an enterohepatic circulation. They are often termed phytoestrogens because they bind to the estrogen receptors although weakly compared to physiologic estrogens. This estrogenicity is not the only mechanism by which isoflavones may have bioactivity-they inhibit tyrosine kinases, have antioxidant activity, bind to and activate peroxisome proliferator regulators alpha and gamma, inhibit enzymes in steroid biosynthesis, strongly influence natural killer cell function and the activation of specific T-cell subsets, and inhibit metastasis. These various properties may explain the much lower incidence of hormonally-dependent breast cancer in Asian populations compared to Americans and Europeans.

[TanyaRD]

It is nice to see this here. It has been interesting to watch these recommendations evolve in the 8 years I have been in oncology. Initially, we told all women with a history of hormone positive cancer to avoid all soy. Gradually, especially in the last year or two, we have the evidence needed to increase those recommendations to include soy in the diet. I still recommend only whole food sources rather than supplement powders or parts of soy in supplement form (i.e. genistein) since we don't really know how individual components behave.

Thanks for posting.

[ElaineM]

I agree about whole food soy like edamane (real soybeans). I tend to eat them more than other forms like tofu or soy milk. I eat miso soup when I catch cold, because it is so comforting. So many other foods have hiddlen soy. I try to stay away from that stuff as much as possible. Everything in moderation.
It never made sense to me when health care workers told Western women to stay away from all soy. Asian women eat alot of soy and they generally have less breast cancer than Western women have. Only a small percentage of breast cancers are related to family history, so there must be other dietary or environmental factors involved other than soy.

[Jackie07]

My Mother must have been around 50 when she began to cook 'soy beans with pig heart'. Wondered if that's a traditional/common recipe for Chinese women to alleviate their menopausal symptoms.

I only remember (I would be around 12) she told me that soy beans are effective in preventing bad ordor/sweat in the foot...

[Rich66]

Reading the above, not sure they have controlled for her2/Er pos BC:

Carcinogenesis. 2010 Jan 12. [Epub ahead of print]
Genistein Induces Enhanced Growth Promotion in ER Positive/erbB-2 Overexpressing Breast Cancers by ER-erbB-2 crosstalk and p27/kip1 Downregulation.

Yang X, Yang S, McKimmey C, Liu B, Edgerton S, Bales W, Archer L, Thor AD.
Department of Pathology, University of Oklahoma Health Sciences Center.
Genistein is a major isoflavone with known hormonal and tyrosine kinase modulating activities. Genistein has been shown to promote the growth of estrogen receptor (ER) positive MCF-7 cells. In ER negative/erbB-2 overexpressing cells, genistein has been shown to inhibit cell growth through its tyrosine kinase inhibitor activity. The effects of genistein on cell growth and tamoxifen response in ER positive/erbB-2 altered breast cancers (known as luminal type B and noted in approximately 10-20% of breast cancers) have not been well explored. Using erbB-2 transfected ER+ MCF-7 cells, we found that genistein induced enhanced cellular proliferation and tamoxifen resistance when compared to control MCF-7 cells. These responses were accompanied by increased phosphorylation of ERalpha and ER signaling, without increase in ER protein levels. Genistein treated MCF-7/erbB-2 cells also showed enhanced activation/phosphorylation of erbB-2, Akt and MAPK/Erk. Blockade of the PI3K and/or MAPK pathways abrogated genistein induced growth promotion, suggesting that genistein effects involve both critical signaling pathways. We also found that p27/kip1 was markedly downregulated in genistein treated MCF-7/erbB-2 cells. Overexpression of p27/kip1 attenuated genistein mediated growth promotion.



In aggregate, our data suggest that the concomitant co-expression of ER and erbB-2 makes breast cancers particularly susceptible to the growth promoting effects of genistein across a wide range of doses. The underlying mechanisms involve enhanced ER-erbB-2 crosstalk and p27/kip1 downregulation.

PMID: 20067990 [PubMed - as supplied by publisher]

[Jackie07]

Anticancer Drugs. 2011 Mar;22(3):253-61.
Additive effects of trastuzumab and genistein on human breast cancer cells.

Lattrich C, Lubig J, Springwald A, Goerse R, Ortmann O, Treeck O.
Source

Department of Obstetrics and Gynecology, University Medical Center Regensburg, Regensburg, Germany.

Abstract

Soy isoflavone genistein, a tyrosine kinase inhibitor and agonist of estrogen receptor-β (ERβ), is known to have antitumoral properties. Given that ERβ often is coexpressed with HER2 in breast cancer, both functions of genistein might be able to enhance the antitumoral action of trastuzumab. In this in-vitro study, we tested whether combined treatment with genistein and trastuzumab exerts additive effects on breast cancer cells. HER2-overexpressing breast cancer cell lines were treated with genistein alone and in combination with trastuzumab. The effects of this treatment on proliferation and gene expression were analyzed. Treatment with high-dose genistein (10 μmol/l) significantly increased the growth-inhibitory effect of trastuzumab on HER2-overexpressing, ERα/β-positive BT-474 breast cancer cells. Combinatory treatment using lower doses of trastuzumab exerted similar effects as a single treatment with standard doses of this drug. In contrast, this effect was absent in ERα-negative SK-BR-3 cells. Similar results were obtained after cotreatment with the ERβ agonist, 2,3-bis(4-hydroxyphenyl)propionitrile. The growth-inhibitory effect of both drugs was accompanied by an increased expression of the putative tumor suppressor ERβ variant, cx, and their combination further elevated mRNA levels of this receptor. In conclusion, genistein significantly enhanced the antitumoral effect of trastuzumab on BT-474 breast cancer cells in vitro. The relevance of these data particularly for women with HER2-overexpressing and ERα/β-positive breast cancer has to be verified in animal or clinical studies.

[Rich66]

Thanks Jackie,
Hmmm. The abstract I referred to uses a different cell line and used Genistein alone.

The study you posted says

"HER2-overexpressing breast cancer cell lines were treated with genistein alone and in combination with trastuzumab."

But..the abstract at least (I think) does not mention the response to genistein alone...just that along with varying levels of Herceptin. The other issue is the level of genistein used. There seems to be research showing that super high doses of a cancer "food" can essentially overdose the cancer cell.

Dunno, given the body of research identifying her2/Er crosstalk not convinced soy is a safe option yet for her2/ER+.

Sure would be nice if it were.

[Rich66]

J Biol Chem. 2011 Apr 14. [Epub ahead of print]
Genistein stimulates MCF-7 [ER+] breast cancer cell growth by inducing acid ceramidase (ASAH1) gene expression.

FREE TEXT

Lucki NC, Sewer MB.
Source

Georgia Institute of Technology, United States;

Abstract

Sphingolipid metabolites, such as ceramide (cer), sphingosine (SPH), and sphingosine-1-phosphate (S1P), contribute to multiple aspects of carcinogenesis including cell proliferation, migration, angiogenesis, and tumor resistance. The cellular balance between cer and S1P levels, for example, is an important determinant of cell fate, with the former inducing apoptosis and the later mitogenesis. Acid ceramidase (ASAH1) plays a pivotal role in regulating the intracellular concentration of these two metabolites by hydrolyzing cer into SPH, which is rapidly phosphorylated to form S1P. Genistein is a phytoestrogen isoflavone that exerts agonist and antagonist effects on the proliferation of estrogen-dependent MCF-7 cells in a dose-dependent manner, primarily as a ligand for estrogen receptors (ER). Genistein can also activate signaling through GPR30, a G-protein coupled cell surface receptor. Based on the relationship between bioactive sphingolipids and tumorigenesis, we sought to determine the effect of genistein on ASAH1 transcription in MCF-7 breast cancer cells. We show herein that nanomolar concentrations of genistein induce ASAH1 transcription through a GPR30-dependent, pertussis-toxin sensitive pathway that requires the activation of c-Src and extracellular-signal regulated kinase 1/2 (ERK1/2). Activation of this pathway promotes histone acetylation and recruitment of phospho-ERα and Sp1 to the ASAH1 promoter, ultimately culminating in increased ceramidase activity. Finally, we show that genistein stimulates cyclin B2 expression and cell proliferation in an ASAH1-dependent manner. Collectively, these data identify a mechanism through which genistein promotes sphingolipid metabolism and support a role for ASAH1 in breast cancer cell growth.



Nutr Res. 2011 Feb;31(2):139-46.
Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor α-negative breast cells.

LINK

Seo HS, Ju JH, Jang K, Shin I.
Source

Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, South Korea; Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.

Abstract

In this study, we investigated the underlying mechanism by which phytoestrogens suppress the growth of normal (MCF-10A) and malignant (MDA-MB-231) estrogen receptor α (ERα)-negative breast cells. We hypothesized that phytoestrogen inhibits the proliferation of ERα-negative breast cancer cells. We found that all tested phytoestrogens (genistein, apigenin, and quercetin) suppressed the growth of both MCF-10A and MDA-MB-231 cells, as revealed by proliferation assays. These results were accompanied by an increase in the sub-G0/G1 apoptotic fractions as well as an increase in the cell population in the G2/M phase in both cell types, as revealed by cell cycle analysis. When we assessed the effect of phytoestrogens on the level of intracellular signaling molecules by Western blot analysis, we found that phytoestrogens increased the level of active p53 (phospho-p53) without changing the p53 level in both MCF-10A and MDA-MB-231 cells. Phytoestrogens also induced an increase in p21, a p53 target gene, and a decrease in either Bcl-xL or cyclin B1 in both cell types. In contrast, the protein levels of phosphatase and tensin homolog, cyclin D1, cell division control protein 2 homolog, phospho-cell division control protein 2 homolog, and p27 were not changed after phytoestrogen treatment. Our data indicate that phytoestrogens induce apoptotic cell death of ERα-negative breast cancer cells via p53-dependent pathway and suggest that phytoestrogens may be promising agents in the treatment and prevention of ERα-negative breast cancer.
Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:21419318 [PubMed - in process]

Seems like a definite risk in ER+ and potentially helpful in ER-...with the caveat that ER status can be mixed within a tumor or changeable over time.

[trasia]

hi Rich,
from Dr. John Lee's book (What your Doctor does not tell you about breast cancer)...Genistein is higher for fermented soy such as natto, tempeh and miso.. for all other type of soy products Genistein is lower and also have more of the less beneficial components.

So, it seems it is a matter of choosing the fermented soy products to get benefit from it Genistein and avoiding all unferemented soy products (specially whole soya bean and soy bean oil)

just my few cents worth..

[Rich66]

Yeah..if you are sure the genistein is beneficial, go for the most concentrated/potent source. To me, the benefit vs harm issue is still cloudy.

[harrie]

http://www.medicinenet.com/script/ma...iclekey=142745

Here is another article supporting the consumption of soy.

[Jackie07]

http://www.webmd.com/diet/omega-3-dh...nal_dab_042511

One of the slides is about how soy food is a good source of omega-3.

Janet Plant gives a succinct overview of the research on soy and breast cancer in her book "Your Life in Your Hands". She concludes that soy consumption is beneficial.
However, her main recommendation is to eliminate all forms of dairy since these contain harmful growth factors. This argument is contrary to what most hospital dieticians recommend....but having read her book and the evidence that backs it up - references to over 450 research studies - I'm clear about where to put my trust!