Headlines on soy and breast cancer can be confusing

Soy and Breast Cancer: How to Put Headlines in Context of Overall Research

Questions about soy and breast cancer are among the most-asked questions when I’m asked to speak about how diet and lifestyle can reduce breast cancer risk. And that’s true whether I’m speaking to health professionals, cancer survivors, or the general public.

Are soy foods protective? Is soy a risk? Should breast cancer survivors avoid it?

 

Key Take-Away Points

Back-and-forth headlines on soy and breast cancer risk resulted from laboratory studies focused on “phytoestrogen” chemical structure and studies in isolated cells and rodents. These studies lay important groundwork for later research. But as this earlier research keeps circulating on the internet, it leads to a lot of confusion and fear.
Human studies are essential to put headlines from laboratory studies in context. Current research does not support fears of increased risk of hormone-related cancers from soy foods. In fact, human studies show potential for lower risk of several cancers, although findings are inconsistent, and evidence is graded as limited.
Research on soy for breast cancer survivors is especially important to better understand whether soy foods are a risk, a protector, or neutral. Enough studies in breast cancer survivors have now been done to provide some answers, though further research is clearly needed.
ER+ breast cancer survivors may have the most questions about including soy foods. Details influence how studies can be interpreted, so a checklist of considerations can be helpful for translating this research.

 

The Back-and-Forth Headlines on Soy and Breast Cancer Risk 

Statements about soy — both positive and negative – often involve phytochemicals (natural plant compounds) it contains known as isoflavones (primarily one called genistein).

What prompted all the interest in soy and breast cancer?

  • Breast cancer was much less common among Asian women compared to U.S. and other Western populations, especially decades ago. Comparing traditional diets in Asia and other areas, soy food consumption was one clear difference.
  • Isoflavones became known as phytoestrogens because their chemical structure is similar to human estrogen, and they can bind to body estrogen receptors. Scientists wondered if soy isoflavones occupying estrogen receptors on cells would reduce availability of the receptors to endogenous (body-produced) estrogen, and thus reduce development of estrogen-related cancers.
  • Oh-oh: Then some lab studies suggested that genistein increased growth of isolated estrogen receptor-positive breast cancer cells and stimulated growth of mammary cancer in rodents. Since high levels of estrogen in postmenopausal women are associated with increased risk of breast cancer, these laboratory findings led to concern that increased exposure to phytoestrogens might pose risk, rather than offer protection.

Progress in Research on Soy, Phytoestrogens, and Breast Cancer Risk 

Studies digging deeper highlight the importance of not jumping to conclusions. research on soy and breast cancer includes laboratory studies of isoflavone compounds

  • Results from animal studies don’t necessarily apply to cancer risks (or benefits) in humans. Rats and mice metabolize isoflavones differently than humans. So the harmful effects seen in rodents related to their high blood levels of activated isoflavones aren’t grounds for expectations in humans. Likewise, some of the protective effects seen in cell studies involved concentrations of isoflavones higher than would occur when people eat soy foods.
  • Estrogen receptors differ. Activation does not always promote cancer development. Some types of estrogen receptors may even suppress growth and reproduction of cancer cells or increase response to cancer treatment.
    Estrogen receptor-alpha (ER-alpha) is common in breast cancer tissue. When it is activated by estrogen, it leads to increased expression of genes that promote cell growth and reproduction.
    ER-beta, in contrast, is common in normal breast cells and often decreases in breast cancer cells. Research has suggested that activation of ER-beta leads to expression of genes that suppress tumor growth, but much remains to be learned. Isoflavone compounds reportedly have a stronger affinity for (are more likely to bind to) ER-beta than ER-alpha.
  • Isoflavones’ influence extends beyond estrogen-related mechanisms. In cell and animal studies, isoflavone effects on gene expression and cell signaling increase activity of antioxidant, anti-inflammatory and carcinogen-deactivating enzymes. In these laboratory studies, isoflavones inhibit cancer cell growth and activate signaling that leads to self-destruction of abnormal cells.

Importance of Human Studies: The Key to Put Headlines in Context

Laboratory studies with cells and animals allow scientists to test hypotheses about mechanisms and how individual components of food might affect steps in the development of cancer. But – despite the headlines that sometimes appear — findings from laboratory studies do not demonstrate effects in people. Group of women reminds us that human studies on soy and breast cancer in diverse groups are vital

Breast cancer risk? Overall, population studies tend to link greater consumption of traditional soy foods (like tofu) with lower breast cancer risk. However, these findings come mainly from Asia, where most women consume moderate amounts of soy throughout life, rather than from studies in Western populations.

What about overall cancer risk? An analysis of 35 prospective cohort studies (observational studies that followed people over time) found that people who consumed more soy foods or more soy isoflavones had lower risk of cancer (of all types) than people who consumed the least.

  • Among specific cancer types, higher intake of soy foods and isoflavones was related to lower risk of lung and prostate cancers. No difference in risk of breast cancer was observed.
  • Cancer mortality showed no association with dietary intake of soy or soy isoflavones – whether among all study participants or specifically among those who developed cancer.
  • Don’t take this association at face value. As described above, laboratory studies show that soy isoflavones could affect cancer development both through cell signaling and other mechanisms that activate antioxidant, anti-inflammatory, immune system, and other defenses against cancer.
    → Most of the studies linking higher soy food consumption with lower cancer risk adjusted for possible influence of factors like age, smoking, and obesity (BMI); some also adjusted for additional factors like alcohol, physical activity, and family history of cancer. People who differ in soy food consumption may differ in other ways – both differences in diet (for example, meat and vegetable consumption) and other factors that influence cancer risk.

Overall, the American Institute for Cancer Research (AICR) and American Cancer Society (ACS) classify evidence as too limited to draw conclusions about soy foods in reducing cancer risk.

Cancer Protection with Soy Foods? Why Research is So Complicated

Making sense of research on soy and cancer risk or survivorship is complexSoy foods, such as tofu, tempeh, edamame and soymilk, are safe and do not pose cancer risk. But is including soy foods as part of your healthy eating habits “neutral” in effect, or can it actually help reduce breast cancer risk?

The answer may not be the same for everyone.

  • Research now suggests that hormone-related protection against breast cancer may relate to soy consumption before or around puberty as breast cells are in transition to their mature form.
  • Soy foods may affect cancer risk in some of us more than in others, due to individual genetic differences in how soy compounds are metabolized. Differences in the types of gut bacteria that ferment soy compounds could also explain why some people may benefit more than others.
  • Population studies often divide participants into four or five groups based on how much of a particular food they consume. Interpreting these findings correctly makes it important to consider how much the “high” and “low” consumers are each eating. In studying soy, the amount consumed by “high” consumers in the U.S. is quite different from “high” consumption in Asia. That may also be part of why findings in these two groups may differ.

 

A Closer Look at Research on Soy for Breast Cancer Survivors 

Breast cancer survivors often have questions about soy foodsYears ago, we didn’t have studies about soy that included large numbers of breast cancer survivors. Following the long-standing standard of medical care — first, do no harm – the message to breast cancer survivors about soy was one of caution in case it might pose risk. Women who had Estrogen Receptor-positive (ER+) cancer, especially if taking tamoxifen (a medication that works through estrogen receptors), were often warned to be extra-cautious about any food with soy… just to be on the safe side.

Today, however, we have evidence from six large population studies and two major analyses that pull together multiple studies. Here’s what they show:

  • A trend for lower all-cause mortality: Each 2 mg/day higher consumption of isoflavones was associated with a 4% lower rate of deaths from all causes, in analysis for the AICR/WCRF CUP Global report on breast cancer survivors.
    → The association did not reach statistical significance (it could have occurred by chance) and the expert panel graded this evidence as Limited Suggestive. That means it’s not strong enough to support a recommendation about soy consumption.
  • No association with breast cancer-specific mortality: Comparing high versus low intake of isoflavones showed no significant association with deaths from breast cancer.
    → Again, there was a trend suggesting possible lower risk, but this could be related to chance.
  • Possible lower breast cancer recurrence: Women with higher isoflavone consumption had a 25% lower risk of recurrence compared to women with lowest intake in a pooled analysis for the CUP Global report.
    → This association was statistically significant [confidence interval is 0.61-0.92]. Still, this evidence is graded Limited Suggestive, and the report does not include a recommendation about soy food consumption for breast cancer survivors.

Soy for ER+ Breast Cancer Survivors? Checklist for Translating the Research

A checklist of factors on consider helps in reviewing studies on soy foods and cancerpoint 1 to checkWas the study in an Asian or Western population? In studies conducted in Asian populations, greater soy consumption is more likely to have associations with reduced breast cancer recurrence, breast cancer mortality, and overall mortality that are statistically significant.

 

  • Lifelong consumption of soy is common among women in Asia. Some research suggests potential protective effects on developing mammary tissue with soy consumption during adolescence.
  • Equol is a compound formed by the gut microbiome from one of the soy isoflavone compounds. People of Asian ethnicity are more likely than Westerners to have a gut microbiome that produces equol. Research is still exploring how much of any protection from soy isoflavones stems from the effects of equol.
  • How high is high consumption? As dietary patterns change, differences in soy consumption between Asian and Western populations may become smaller. But especially in studies that reflect consumption over a decade ago, consumption of soy foods in the U.S. was very low, so that even a couple servings of soy foods per week would be categorized as “high” consumption. But in Asia, one to two servings of soy foods per day has been typical, and “high” consumption may mean more than that.

 

point 2 to considerWhat is the overall diet quality, especially in studies in the U.S. and Europe? People who eat more whole soy foods may eat an overall dietary pattern more aligned with cancer prevention recommendations.

Processed forms of soy are increasingly included in cereals, bars, and other processed foods. Contrary to fears that these are ultra-high in isoflavones, these soy ingredients are usually substantially lower in isoflavones and dietary fiber. People who include soy mainly in foods high in added sugars and low in elements that support good health should be considered separately from people eating whole soy foods as part of a high-quality plant-based diet.

 

Point 3 to checkWhat about women who have had ER+ breast cancer? Much of the fear about soy consumption after breast cancer comes back to concerns about isoflavones as “phytoestrogens.” However, even in studies of U.S. breast cancer survivors (most likely not lifelong soy consumers), women who had ER+ breast cancer show either decreased recurrence or decreased deaths related to moderate consumption of soy foods… or no effect. None show an increase in risk of poor outcomes for ER+ women, including women using tamoxifen.

 

point 4 to checkIs the study of soy food consumption or supplementary isoflavones? There isn’t any evidence to support the use of soy isoflavones provided by supplements or other isolated elements of soy (like soy protein powder) to reduce cancer risk. So don’t translate findings of studies that analyze associations of soy consumption using isoflavone or protein content as any indication that those individual components offer protection.

 

Key point: In studies that show lower risk of recurrence or overall mortality among “high” soy food consumers, this does not refer to massive amounts of soy. Today’s research prompts us to look at what including soy foods means for overall diet quality. 

 

What is “moderate” consumption of soy foods? And what about the soy protein being added to so many breads, bars and other foods? Check back for Part 2 to dig into these important practical questions!

 

Bottom Line on Soy and Breast Cancer Research

Talking about soy foods and cancer risk or survivorship provides a great example of how laboratory studies can provide hints of how food choices might influence cancer development, but cannot be directly translated into sound dietary advice. Research shows multiple ways that isoflavone compounds found in soy foods could reduce cancer risk, acting through apparently protective estrogen receptors (ER-beta) and through other pathways.

The big picture of research has now resolved fears that soy foods could increase risk of estrogen-sensitive cancer or threaten poor outcomes after a cancer diagnosis. But evidence does not yet support benefits for cancer prevention or outcomes from including more soy foods. It’s possible that some people will benefit more than others from consuming soy, and research continues. Meanwhile, when considering potential benefits, consider how moderate consumption of soy foods would fit in and promote an overall healthy dietary pattern.

 

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Resources

Need a quick read to share with clients or family that explains how research on soy foods and cancer has evolved? Share this article I wrote for AICR, Soy and Cancer: Myths and Misconceptions.

For a summary of research about soy foods and cancer risk in the context of recommendations for a diet to reduce cancer risk, check the American Institute for Cancer Research (AICR) website. You’ll also find help here for addressing questions about soy for breast cancer survivors.

The most recent nutrition guidelines for cancer survivors from the American Cancer Society also indicate no apparent harmful effects of soy consumption on breast cancer recurrence or survival.  Each breast cancer survivor should make decisions about these matters in discussion with her personal physician; these materials may be helpful to read ahead and share.

References

Becerra-Tomás N, Balducci K, Abar L, et al. Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis. Int J Cancer. 2023 Feb 15;152(4):616-634. doi: 10.1002/ijc.34321.

Caan BJ, Natarajan L, Parker B, et al. Soy food consumption and breast cancer prognosis. Cancer Epidemiol Biomarkers Prev. 2011 May;20(5):854-8. doi: 10.1158/1055-9965.EPI-10-1041.

Chen P, Li B, Ou-Yang L. Role of estrogen receptors in health and disease. Front Endocrinol (Lausanne). 2022 Aug 18;13:839005. doi: 10.3389/fendo.2022.839005.

Drummond AE, Swain CTV, Brown KA,et al. Linking Physical Activity to Breast Cancer via Sex Steroid Hormones, Part 2: The Effect of Sex Steroid Hormones on Breast Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2022 Jan;31(1):28-37. doi: 10.1158/1055-9965.EPI-21-0438.

Fan Y, Wang M, Li Z, et al. Intake of Soy, Soy Isoflavones and Soy Protein and Risk of Cancer Incidence and Mortality. Front Nutr. 2022 Mar 4;9:847421. doi: 10.3389/fnut.2022.847421.

Gerhauser C. Impact of dietary gut microbial metabolites on the epigenome. Philosophical Transactions of the Royal Society B: Biological Sciences. 2018;373(1748):20170359.

Guha N, Kwan ML, Quesenberry CP Jr, et al. Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res Treat. 2009 Nov;118(2):395-405. doi: 10.1007/s10549-009-0321-5.

Jiang Y, Gong P, Madak-Erdogan Z, et al. Mechanisms enforcing the estrogen receptor β selectivity of botanical estrogens. FASEB J. 2013 Nov;27(11):4406-18. doi: 10.1096/fj.13-234617.

Messina M, Duncan A, Messina V, Lynch H, Kiel J, Erdman JW Jr. The health effects of soy: A reference guide for health professionals. Front Nutr. 2022 Aug 11;9:970364. doi: 10.3389/fnut.2022.970364.

Messina M, Hilakivi-Clarke L. Early intake appears to be the key to the proposed protective effects of soy intake against breast cancer. Nutr Cancer. 2009;61(6):792-8. doi: 10.1080/01635580903285015.

Montgomery M, Srinivasan A. Epigenetic Gene Regulation by Dietary Compounds in Cancer Prevention. Advances in Nutrition. 2019;10(6):1012-1028.

Rock CL, Thomson C, Gansler T, et al. American Cancer Society guideline for diet and physical activity for cancer prevention. CA: a cancer journal for clinicians. 2020;70(4): 245-271. doi:10.3322/caac.21591

Setchell KD, Brown NM, Zhao X, et al. Soy isoflavone phase II metabolism differs between rodents and humans: implications for the effect on breast cancer risk.  Am J Clin Nutr, 2011. 94(5):1284-94.

Sung H, Rosenberg PS, Chen WQ, et al. Female breast cancer incidence among Asian and Western populations: more similar than expected. J Natl Cancer Inst. 2015 Apr 13;107(7):djv107. doi: 10.1093/jnci/djv107.

Takano EA, Younes MM, Meehan K, et al. Estrogen receptor beta expression in triple negative breast cancers is not associated with recurrence or survival. BMC Cancer. 2023 May 19;23(1):459. doi: 10.1186/s12885-023-10795-5.

USDA Database for the Isoflavone Content of Selected Foods, Release 2.1. November 2015.

World Cancer Research Fund/American Institute for Cancer Research. Diet, Nutrition, Physical Activity and Cancer: A Global Perspective. Continuous Update Expert Report. 2018. Available at: https://wcrf.org/dietandcancer

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4 Comments

  1. Dina on August 14, 2023 at 1:02 pm

    Karen,

    Your information is always spot-on and succinct! Thank you for your incredible contribution to the field of nutrition and dietetics over the years. We met back in the 90’s or early 2000s (and we’re both Cornellians and both write for TD…) but I’ve followed you for decades. You continue to inspire me!

    Dina Aronson, MS, RDN

    • Karen Collins on August 14, 2023 at 4:58 pm

      I’m so glad this review of the research on soy and breast cancer is helpful to you, Dina. And thank you for the positive feedback on my efforts to support the vital work dietitians do. 🙂

  2. […] review of clinical trials of time-restricted eating found that studies with eating periods that started and ended earlier in […]

    • Karen Collins on March 6, 2024 at 5:42 pm

      Thanks for the positive feedback, Isabella. I’m so glad you found it helpful. There is a lot of research — and it will continue to grow — so it will be helpful to hold some of these key questions in mind.
      Have you been using some form of chrononutrition yourself or with clients? Keep me posted on your perspective and experience!

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Meet the author/educator

Karen Collins
MS, RDN, CDN, FAND

I Take Nutrition Science From Daunting to Doable.™

As a registered dietitian nutritionist, one of the most frequent complaints I hear from people — including health professionals — is that they are overwhelmed by the volume of sometimes-conflicting nutrition information.

I believe that when you turn nutrition from daunting to doable, you can transform people's lives.

Accurately translating nutrition science takes training, time and practice. Dietitians have the essential training and knowledge, but there’s only so much time in a day. I delight in helping them conquer “nutrition overwhelm” so they can feel capable and confident as they help others thrive.

I'm a speaker, writer, and nutrition consultant ... and I welcome you to share or comment on posts as part of this community!

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