As you tuck into a delightful tofu and veggie stir-fry, or maybe even some tofu ice-cream, is there a lingering doubt? Is this really doing me good? Am I contributing to the prevention of breast and prostate cancer, or am I, as some would have us believe, contributing to their increased likelihood?
If so, you need the answer to this question: Do the phyto-oestrogens in soybeans act like oestrogen or Tamoxifen? Need a full explanation? Let us go Out on a Limb again, follow on from the earlier post this week where we explored the soybean itself, and using the evidence-base available, explore how cancer and soy beans interact, but first
Thought for the day
The doctor of the future will give no medicine,
But will instruct his patient in the care of the human frame,
In diet and in the cause and prevention of disease
Thomas Edison, 1902
WHY LINK SOY and BREAST CANCER?
1. There are historically low breast cancer incidence rates in Asia, where traditional soyfoods are a staple.
2. Research demonstrates isoflavones in soy may exert anti-oestrogenic effects.
3. Some epidemiologic data shows a higher soy intake results in a lower breast cancer risk.
4. Rodent studies demonstrate soy protects against carcinogen-induced mammary cancer.
HOW BREAST CANCER is AFFECTED by OESTROGEN
In broad terms, there are 2 types of breast cancer; oestrogen positive and oestrogen negative. Our discussion relates to oestrogen positive cancers in particular and these make up about 70% of all breast cancers.
Oestrogen positive cancers are aggravated by oestrogen (the main female sex hormone). How this happens is that on the surface of oestrogen positive cancer cells there are receptors for oestrogen. When an oestrogen molecule comes into proximity with such a receptor, it attaches (but does not go into the cell) and creates a cascade of reactions within the cell that speeds up the cancer’s progression.
In earlier times, removal of the ovaries was attempted as a way to reduce oestrogen levels in women with breast cancer. But oestrogen is made in other parts of the body, so only in exceptional circumstances has this proven useful.
Many people will have heard of tamoxifen. This was heralded as a breakthrough drug as, while it does attach to the oestrogen receptors, it does not cause the internal reaction. Therefore, tamoxifen blocks natural oestrogen from having its adverse affects.
Unfortunately, tamoxifen does aggravate uterine tissue and is associated with increased uterine cancer, but on balance it remains a widely used anti-cancer drug. Simply put, tamoxifen is an oestrogen antagonist.
WHAT OESTROGEN IS IN SOY?
There are 3 main oestrogen-like chemicals in soybeans; genistein, daidzein, and glycitein.
They are present in their beta glycoside forms: genistin, daidzin, and glycitin, hence you may see them written differently.
Genistin/genistein, daidzin/daidzein, and glycitin/glycitein account for approximately 50–55%, 40–45%, and 5–10% of total isoflavone content, respectively in soybeans.
Older adults in Japan and Shanghai, China, typically consume between 25 and 50 mg/day of isoflavones and probably no more than 5% of these populations consume more than 100 mg/day. In contrast, people in the United States and Europe consume an average of less than 3 mg/day.
Isoflavones have a chemical structure similar to human oestrogen but bind to estrogen receptors more weakly. Significantly, it has been suggested that genistein, which is the best-studied isoflavone, along with the other isoflavones may act like tamoxifen as estrogen receptor blockers.
What has also drawn attention in recent years are conflicting concerns that isoflavones may stimulate the growth of existing estrogen-sensitive breast tumors. These concerns are based on evidence gathered from studies involving tissue cultures and rodents. However, they do contrast with the human epidemiological evidence that shows among Asian women higher soy intake is associated with a nearly one-third reduction in breast cancer risk and that Japanese breast cancer patients, in comparison to Western women, exhibit better survival rates even after controlling for stage of diagnosis.
SOY for the PREVENTION of BREAST CANCER
In Asia, isoflavones are consumed as traditional soy foods and not in pure or processed forms. Epidemiological data associates lifetime, and particularly pre-adolescent consumption of traditional soy with a decreased risk of breast cancer development in humans.
An Asian-American study on soy found that women, pre- and postmenopausal, who consumed tofu, had a 15% reduced risk of breast cancer with each additional serving per week.
Wu AH, Ziegler, et al. Tofu and risk of breast cancer in Asian- Americans. Cancer Epidemiol Biomarkers Prev. 1996;5(11):901-906.
Another trial reported that women in the highest tertile intake of tofu had a 51% decrease risk of premenopausal breast cancer when compared with women in the lowest tertile. In this study, no statistical significant association was observed between soy intake and breast cancer risk among postmenopausal women.
Hirose K, Imaeda N, Tokudome Y, Goto C, Wakai K, Matsuo K, et al. Soybean products and reduction of breast cancer risk: a case-control study in Japan. Br J Cancer 2005;93(1):15-22.
Messina and colleagues published a major review on this subject in 2008 and I consider it to be one of the very the best review articles on this topic. To quote:
The conclusion drawn from this extensive review of the available literature is that currently there is little evidence to suggest that any potential weak estrogenic effects of dietary isoflavones have a clinically relevant impact on breast tissue in healthy women. Limited data suggest this is also the case for breast cancer survivors.
This evidence includes multiple trials showing no effects on breast proliferation or mammographic density and considerable epidemiologic data showing either no effect or a modest protective role of soy/isoflavone intake on breast cancer risk.
Based on this evidence it seems unlikely that isoflavone consumption at dietary levels (i.e. <100 mg/day) elicits adverse breast cancer-promoting effects in healthy women or breast cancer survivors not undergoing active treatment.
Messina MJ and Wood CE; Nutrition Journal 2008. To read in full, CLICK HERE http://www.nutritionj.com/content/7/1/17
SOY and its AFFECTS on BREAST CANCER
When this article was first posted in 2008, there was no data to support the notion that soyfoods or isoflavone supplements could improve the survival of breast cancer patients.
Several earlier studies suggested that whole soy foods appeared to have no negative or positive effect on breast cancer. For example the following two studies found soy foods had no negative impact on breast cancer survival.
Boyapati SM, et al. Soyfood intake and breast cancer survival: a followup of the Shanghai Breast Cancer Study. Breast Cancer Res Treat. 2005;92(1):11-17.
Nishio K, et al. Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study. Cancer Causes Control. 2007;18(8):801-808.
This, and other evidence, prompted Messina and colleagues in their 2008 review quoted above to state:
Available data on breast cancer recurrence and mortality provide some assurance for breast cancer patients that soyfoods/isoflavone supplements, when taken at dietary levels, do not contribute to recurrence rates although more data are clearly needed to better address this issue.
However, in 2009, following more analysis of the Shanghai study, strong new evidence was published showing significant benefits of consuming soy for women with breast cancer in terms of better survival and less cancer recurrence, making Messina’s claim outdated.
Women consuming soy in the highest quartile had a 29% lower death rate over the 4 year follow up, and 32% reduced risk of recurrence. The protective effect was present regardless of oestrogen receptor status of the cancer, or whether tamoxifen was used or not.
This study provided the most compelling evidence to date of a benefit for soy consumption by women with breast cancer (as opposed to no harm). It is important because it shows a benefit for increased soy consumption irrespective of oestrogen receptor status or tamoxifen use.
Shu XO et al. Soy food intake and breast cancer survival; JAMA. 2009 Dec 9; 302(22):2437-43.
The trend of this study was confirmed in 2013 when another study demonstrated soy food intake is associated with longer survival and low recurrence among breast cancer patients.
Zhang, Y.F., et al., Positive effects of soy isoflavone food on survival of breast cancer patients in China. Asian Pac J Cancer Prev, 2012. 13(2): p. 479-482.
More recently still, a major review from the World Cancer Research Fund International’s Continuous Update Project Report: Diet, Nutrition, Physical Activity, and Breast Cancer Survivors has examined a total of 85 studies involving 164,416 women. Included has been analysis of specific evidence related to soy and its interaction with breast cancer.
This major study makes modest conclusions The evidence was sparse and generally consistent, and is suggestive of an inverse relationship between consumption of foods containing soy and all cause mortality.
Translation? From what solid evidence there is so far, it seems that soy is likely to be helpful; the evidence for it being unhelpful is not there. Conclusion? It is coming after a few more pieces of the puzzle are put into place!
BEWARE: NATURAL SOY, PROCESSED SOY – DIFFERENT OUTCOMES
It may be that the non-traditional soy foods do create problems. Significantly, soy protein isolates do not contain many of the bioactive components present in whole soy. As we clarified in Part 1, refined products include soy flour and its processed derivatives.
Research has demonstrated that soy protein isolates (85–90% soy protein) do stimulate the growth of
estrogen-dependent tumors. Another study evaluated the relative effects of different degrees of soy processing on the growth of pre-existing tumors and demonstrated that consumption of isoflavones in increasingly purer or more highly enriched forms may have a proportionally worse effect on estrogen-dependent tumor growth.
Allred CD,et al. Soy processing influences growth of estrogen-dependent breast cancer tumors. Carcinogenesis 2004;25:1649-1657.
Some research has shown that soy processing increases breast cancer growth in mice. This may be related to isoflavone metabolism and bioavailability, but more research is needed.
Allred CD, et al. Soy processing influences growth of estrogen-dependent breast cancer tumors. Carcinogenesis 2004;25:1649-1657.
SOY AND TAMOXIFEN
There has also been some concern expressed that soy products may actually interfere with the action of tamoxifen itself. However, recent studies examining the interaction between soy and tamoxifen have yielded neutral or beneficial findings.
In one study, soy intake had no effect on levels of tamoxifen or its metabolites.
Wu AH, et al. Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer. J Clin Oncol. 2007;25(21):3024-3030.
In another, the combination of tamoxifen and genistein inhibited the growth of human breast cancer cells in a synergistic manner in vitro.
Mai Z, et al. Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor- positive and HER2-overexpressing human breast cancer cells. Mol Carcinog. 2007;46(7):534-542.
SOY and CHEMO
One study reported that soy’s main phyto-oestrogen genistein, enhanced the cytotoxic effect of the chemotherapeutic agent adriamycin at low doses against the human breast cancer cell. This enhancing effect was mainly attributed to the increase of necrotic-like, rather than apoptotic, cell death.
Satoh H, Nishikawa K, Suzuki K, et al. Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent. Res Commun Mol Pathol Pharmacol.2003;113–114:149–158.
SOY and YOUNG GIRLS
Of great interest is research that demonstrates eating soy foods during childhood and adolescence in women, and before puberty onset in animals, appears to significantly reduce the risk of breast cancer later in life.
SYNERGISTIC EFFECTS OF SOY
Research evidence indicates a possible synergistic relationship between soy and green tea consumption.
SOY AND THE AUTHORITIES
The American Cancer Society in 2006 concluded that breast cancer patients can safely consume up to three servings of traditional soyfoods per day, although the group advised against the use of more concentrated sources of isoflavones such as powders and supplements.
The United States Health and Human Services Agency for Healthcare Research and Quality (AHRQ) conducted a review of the available studies and found little evidence of substantial health improvements and no adverse effects, but also noted that there was no long-term safety data on estrogenic effects from soy consumption.
The AHRQ report notes that future studies of the health effects of soy need to better address the complex relationship between health and food components, including how variations in the diets, lifestyles, and health of participants might affect the results.
Also, studies that substitute practical amounts of soy products into people's diets would better address the question of whether people should make the effort to include more soy in their diet.
The Cancer Council of New South Wales released a statement saying scientific research suggests that overall the moderate consumption of soy products does not appear to present a risk to women with breast cancer, and there is equivocal evidence that consuming large amounts of soy products may have a protective effect against developing breast and prostate cancer. However, the Council does not recommend taking soy dietary supplements as there is no evidence they are either effective or safe at preventing or treating cancers.
WHAT RUTH and I DO
We regularly eat organic tofu and soy yoghurt (which Ruth makes from Bonsoy). Ruth drinks small amounts of soymilk (mostly Bonsoy in teas), but I do not – I do not like it and have teas and dandelion coffee black). We eat some tempeh but only have silken tofu by mistake when eating out!
We avoid processed soy products and read labels to avoid the myriad of foods with these products added to them.
MY OWN CONCLUSIONS and RECOMMENDATIONS
In answer to the key question, I conclude the phyto-oestrogens in soy act like tamoxifen, not like oestrogen. I also conclude:
1. Traditional soy foods are almost certainly safe and warrant being a part of a healthy diet for healthy people. I recommend them. I particularly recommend regular soy consumption for young and adolescent girls; but then lifetime consumption seems ideal.
2. Processed or refined or concentrated soy products run the real risk of being problematic for everyone. I do not recommend them.
3. For women with breast cancer, the best evidence currently available suggests traditional soy foods, eaten in traditional amounts are likely to be safe and may well be helpful in reducing recurrences and extending survival. I recommend them.
Coconut oil – are you nuts?
Food for life – what to eat when
You Can Conquer Cancer – the revised edition has many other explanations like this one on soy. What type of protein and how much? Which are the best fats to eat and to avoid, and so on. This book is about prevention and long-term good health, as well as cancer recovery.
Ruth and I leave this week to present our final meditation retreat for the year, Meditation Under the Long White Cloud at Mana retreat centre amidst the peace and beauty of the Coromandel Peninsula in New Zealand.
Then we travel down south to the exquisite landscape at Wanaka to present the 5 day cancer residential program, Mind, Meditation and Healing from November 10 - 14. It will be a delight to be back in New Zealand once more.