Soy & Breast Cancer Research Sheds More Light On The Disease’s Development

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Scientists have explored a lot of factors that might affect the risk of developing breast cancer, including genetics, hormonal birth control, and even the age at which people have their first child. However, one factor that's commonly misunderstood is the influence of soy in your diet. Soy products, including soy milk, tofu, miso, and tempeh, have been shown to have a potentially protective influence that lowers breast cancer risk. Experts tell Bustle that it's not as simple as that, however, and that when it comes to people who've been diagnosed with breast cancer, soy may actually prove to be harmful.

Several studies, including one published in 2015 and another in 2019, found that Japanese women who consumed higher quantities of miso soup and isoflavones, a compound found in soy foods, seemed to experience a lower risk of breast cancer. A study in 2017 also found that dietary levels of isoflavones appeared to reduce deaths in women who had survived breast cancer. Understanding that link is a challenge, though.

"It still remains a mystery why some people get cancer and some don't, even if they appear to have similar risk factors or are engaged in similar protective behaviors and lifestyles," Dr. Leena Hilakivi-Clarke, a professor of oncology at Georgetown University School of Medicine who has published recent research on soy and breast cancer, tells Bustle. "The same compound can have opposite effects on cancer risk depending on when the exposure occurs."

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Dr. Hilakivi-Clarke says that the overall link between soy and a lower risk of breast cancer is pretty undeniable. The particular element of soy that interests a lot of researchers is genistein, a kind of isoflavone found in soy foods. "I don't know exactly why life-long genistein and soy food intake reduces breast cancer risk, but it does," Dr. Hilakivi-Clarke tells Bustle. Science indicates that eating soy products over the course of your life, starting in childhood, seems to have some kind of protective effect. This may seem counter-intuitive, because genistein is a kind of plant estrogen, and we know from other studies that exposure to higher levels of estrogen may increase the likelihood of developing breast cancer.

The key to understanding how soy might be protective, explains Dr. Hilakivi-Clarke, is to know that the body doesn't react to estrogen in one uniform way. When we consume genistein, it increases the levels of estrogen in the body. The body has two types of estrogen receptors, or proteins inside cells which are activated by estrogen: estrogen receptor alpha, and estrogen receptor beta. Genistein "likes estrogen receptor beta more than estrogen receptor alpha, while our own estrogens like these receptors equally," says Dr. Hilakivi-Clarke; in other words, genistein bonds to one receptor more than the other. That choosiness makes a difference, she says, because genistein may inhibit inflammation and boost anti-cancer immune responses, while other estrogens do the opposite. That's the crucial difference between soy and other sources of estrogen, including our own bodies.

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There's another element to soy's potential effects on breast cancer risk: its impact on the gut. "Genistein also has probiotic properties," says Dr. Hilakivi-Clarke. A study in 2017 in mice showed that there could be a link between a diet high in genistein and lowering the severity of breast cancers, but a lot more work needs to be done on this area in order to have this become a recommendation.

When it comes to soy and breast cancer treatment, the story becomes complicated. Dr. Hilakivi-Clarke's own research in 2017 has shown that if you eat a lot of genistein over your lifetime, it may help your response to breast cancer treatment and help you avoid recurrent tumors. "Long term genistein intake seems to improve response to antiestrogen tamoxifen therapy, and prevent recurrence," she tells Bustle.

Experts tell Bustle that people who have the types of breast cancer known as estrogen-receptor positive, or ER-positive, and are being treated for them, shouldn't introduce soy into their diet. These tumors are caused by over-active estrogen receptors, and the more estrogen in their systems, including genistein, the more dangerous the cancer becomes.

"Breast cancer patients are advised to avoid all soy products, including soy milk, soy beans, and edamame, as they will increase the future likelihood of estrogen stimulation, which is not recommended for patients with hormonally sensitive breast cancer," Dr. Jane Mendez, chief of breast surgery at the Miami Cancer Institute, tells Bustle. It's important to note that not all breast cancers are ER-positive; triple-negative breast cancer isn't related to estrogen, and Dr. Mendez says that people with that kind of breast cancer don't need to avoid soy.

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Scientists aren't completely agreed on whether this blanket ban should be maintained for everybody being treated for ER-positive breast cancers. Dr. Hilakivi-Clarke says that her own preliminary studies have shown that if people start eating soy foods after their ER-positive breast tumors have been completely treated, their tumors don't come back — and soy actually seems to help keep them tumor-free. Right now, a lot more work needs to be done to understand how soy affects breast cancer risk, progression, and recurrence.

There are many interesting aspects about the link between soy and breast cancer that still remain to be understood. The immune system and the gut micriobiome seem to influence how soy affects breast cancer, but science hasn't yet discovered how. We're also still understanding how a soy-heavy diet might affect peoples' responses to breast cancer treatment. A lot of other factors can also influence how people react to breast cancer treatment, so it's also unwise to think that soy is the be-all and end-all.

Right now, though, if you're concerned about your soy intake, you need to look at your family history of breast cancers, particularly ER-positive types. "For patients with a familial history of breast cancer, it is advised to consume soy in moderation," Dr. Mendez tells Bustle. For everybody else, it's not something you need to be concerned about— and if you are, talk to your doctor about your individual risks.

Studies referenced:

Gong, L., Li, Y., Nedeljkovic-Kurepa, A., & H Sarkar, F.H. (2003) Inactivation of NF-κB by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene 22 4702–4709. https://www.nature.com/articles/1206583

Liu, R., Yu, X., Chen, X. Hongfei, Z. Liang, C., Xu, X., Xu, W, Chen, Y., Wang, W., Yu, L., Wu, Y., Yan, N., Hu, X. (2019) Individual factors define the overall effects of dietary genistein exposure on breast cancer patients. Nutrition Research, 67, 1-16 https://doi.org/10.1016/j.nutres.2019.03.015

Mahmoud, A. M., Al-Alem, U., Ali, M. M., & Bosland, M. C. (2015). Genistein increases estrogen receptor beta expression in prostate cancer via reducing its promoter methylation. The Journal of steroid biochemistry and molecular biology. 152, 62–75. doi:10.1016/j.jsbmb.2015.04.018

Nomura, S., Hwang, Y. T., Gomez, S. L., Fung, T. T., Yeh, S. L., Dash, C., … Wang, J. H. (2018). Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors. Breast cancer research and treatment, 168(2), 467–479. doi:10.1007/s10549-017-4578-9

Paterni, I., Granchi, C., Katzenellenbogen, J. A., & Minutolo, F. (2014). Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential. Steroids, 90, 13–29. doi:10.1016/j.steroids.2014.06.012

Paul, B., Royston, K.J., Li, Y., Stoll, M.L., Skibola, C.F., Wilson, L.S., Barnes, S., Morrow, C.D., Tollefsbol. T.O. (2017) Impact of genistein on the gut microbiome of humanized mice and its role in breast tumor inhibition. PLoS One, 12(12) doi: 10.1371/journal.pone.0189756.

Soldati, L., Di Renzo, L., Jirillo, E., Ascierto, P. A., Marincola, F. M., & De Lorenzo, A. (2018). The influence of diet on anti-cancer immune responsiveness. Journal of translational medicine, 16(1), 75. doi:10.1186/s12967-018-1448-0

Trock, B.J., Hilakivi-Clarke, L., Clarke, R. (2006) Meta-Analysis of Soy Intake and Breast Cancer Risk. JNCI: Journal of the National Cancer Institute, 98(7) 459–471. https://doi.org/10.1093/jnci/djj102

Wei, Y.,Lv, J., Guo, Y., Bian, Z., Gao, M., Du, H., Yang, L., Chen, Y., Zhang, X., Wang, T., Chen, J., Chen, Z., Yu, C., Huo, D., & Li, L. (2019) Soy Intake and Breast Cancer Risk: A Prospective Study of 300,000 Chinese Women and a Dose-Response Meta-Analysis. The Lancet. https://ssrn.com/abstract=3401983

Yamamoto, S., Sobue, T., Kobayashi, M., Sasaki, S., Tsugane, S. (2003) Soy, isoflavones, and breast cancer risk in Japan. Natl Cancer Inst. 95(12) 906-13. doi: 10.1093/jnci/95.12.906

Yue, W., Wang, J. P., Li, Y., Fan, P., Liu, G., Zhang, N., … Santen, R. (2010). Effects of estrogen on breast cancer development: Role of estrogen receptor independent mechanisms. International journal of cancer, 127(8), 1748–1757. doi:10.1002/ijc.25207

Zhang, F. F., Haslam, D. E., Terry, M. B., Knight, J. A., Andrulis, I. L., Daly, M. B., … John, E. M. (2017). Dietary isoflavone intake and all-cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Cancer, 123(11), 2070–2079. doi:10.1002/cncr.30615

Zhang, F. F., Haslam, D. E., Terry, M. B., Knight, J. A., Andrulis, I. L., Daly, M. B., John, E. M. (2017). Dietary isoflavone intake and all-cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Cancer, 123(11), 2070–2079. doi:10.1002/cncr.30615

Zhang, X., Cook, K. L., Warri, A., Cruz, I. M., Rosim, M., Riskin, J., … Hilakivi-Clarke, L. (2017). Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats. Clinical cancer research : an official journal of the American Association for Cancer Research, 23(3), 814–824. doi:10.1158/1078-0432.CCR-16-1735

Zhao, Ting-Ting et al. (2019) Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Clinical Nutrition. 38 (1) 136 - 145 https://doi.org/10.1016/j.clnu.2017.12.006

Experts:

Dr. Leena Hilakivi-Clarke, Professor of Oncology, Georgetown University School of Medicine

Dr. Jane Mendez, surgical oncologist and chief of breast surgery, Miami Cancer Institute