Beginning in the late 1990s, concerns arose that soy increases breast cancer risk and worsens the prognosis of women with this disease despite the historically low breast cancer incidence rates in soyfood-consuming countries.1 However, observational data published beginning in 2009,2 showed just the opposite, post-diagnosis soy intake was associated with reduced mortality and recurrence.3 A new systematic review of the clinical data by Finkeldey et al.4 shows conclusively that neither soy nor isoflavone intake affects markers of breast cancer risk. Thus, both the observational data and clinical data are supportive of the safety of soy consumption by breast cancer patients, a conclusion that aligns with the positions of independent health agencies including the American Institute for Cancer Research, 5 the American Cancer Society, 6 the Canadian Cancer Society7 and the World Cancer Research Fund International.8
The findings of the review by Finkeldey et al.4 are consistent with past reviews of the clinical data, but this review is more comprehensive, and thus, it adds considerably to the literature. While it may not definitively resolve the soy and breast cancer controversy, it is certainly a step in that direction. Definitive resolution requires a clinical intervention involving women with breast cancer and endpoints of tumor recurrence and breast cancer mortality, not markers of breast cancer risk. The observational data showing benefits of post-diagnosis soy consumption suggests such a trial could be justified, but whether it will be is mere speculation.
A wide variety of markers were examined by Finkeldey et al.,4 including breast density, estrogen and estrogen metabolites, menstrual cycle length and inflammation and breast cell proliferation. While supportive of safety, the lack of effect raises two important questions. One, if markers of breast cancer risk are not affected by soy/isoflavones, why is it that the observational data indicate post-diagnosis soy intake is associated with reduced recurrence and mortality? And two, if markers of breast cancer risk are not affected by soy/isoflavones, how can it be that soy intake reduces risk of developing breast cancer as some observational data suggest is the case?9,10
In regard to prevention, one hypothesis is that for soy to reduce breast cancer risk, intake needs to occur early in life, that is, during childhood and/or adolescence.11,12 Animal research suggests isoflavone exposure, when young, changes cells in the developing breast in a way that makes them permanently less likely to be transformed into cancer cells later in life.13 If this is the case, it is understandable as to why isoflavone or soy intake in trials involving adults does not reveal mechanisms by which breast cancer risk could be reduced. If, for example, early soy intake permanently improved DNA repair mechanisms, this improvement would not be detected in studies examining breast tissue density or in vivo breast cell proliferation in women not exposed to a breast carcinogen.
More difficult to address is this question: If markers of breast cancer risk are not affected by soy/isoflavones, why is it that the observational data indicate post-diagnosis soy intake is association with reduce recurrence and mortality? One obvious explanation is confounding. It is never possible to completely control for confounding variables in observational studies. Therefore, it may be that soy intake is simply a marker for a lifestyle that reduces breast tumor recurrence and mortality and is not protective in and of itself.
While a possibility, because the observational studies involve Asian women, this is less likely to be true. Soy consumption is less reflective of a particular lifestyle in Asia than it is outside of Asia. In contrast, an American regularly consuming soy is likely to adhere to a lifestyle that departs somewhat from his or her non-soy-consuming counterpart. Alternatively, it could be that post-diagnosis soy intake improves the prognosis of women with breast cancer in ways that are not detected in relatively short-term studies evaluating the currently identified markers of breast cancer risk.
The lack of identified mechanism(s) for the benefits of post-diagnosis soy intake highlights the need for caution when making dietary recommendations. On the other hand, the observational data when combined with the results of the systematic review by Finkeldey et al.,4 make a strong argument for the safety of soy consumption by breast cancer survivors.
- Parkin, D.M.; Pisani, P., and Ferlay, J.; Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer. 1999, 80, 827-41.
- Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA. 2009;302:2437-43.
- Chi F, Wu R, Zeng YC, et al. Post-diagnosis soy food intake and breast cancer survival: A meta-analysis of cohort studies. Asian Pacific journal of cancer prevention: APJCP. 2013;14:2407-12.
- Finkeldey L, Schmitz E, Ellinger S. Effect of the intake of isoflavones on risk factors of breast cancer—A systematic review of randomized controlled intervention studies. Nutrients. 2021.
- American Institute for Cancer Research Soy: Intake does not Increase risk for breast cancer survivors (accessed August 6, 2021). https://www.aicr.org/cancer-prevention/food-facts/soy/. 2021.
- Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62:242-74.
- Eating well after breast cancer. (Accessed October 25, 2019, 2019, at https://www.cancer.ca/en/cancer-information/cancer-type/breast/supportive-care/eating-well-after-breast-cancer/?region=on.)
- World Cancer Research Fund International. Continuous Update Project Report: Diet, Nutrition, Physical Activity, and Breast Cancer Survivors. 2014. Available at: www.wcrf.org/sites/default/files/Breast-Cancer-Survivors-2014-Report.pdf. Accessed December 10, 2014. 2014.
- Okekunle AP, Gao J, Wu X, et al. Higher dietary soy intake appears inversely related to breast cancer risk independent of estrogen receptor breast cancer phenotypes. Heliyon. 2020;6:e04228.
- Zhao TT, Jin F, Li JG, et al. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Clin Nutr. 2019;38:136-45.
- 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;61:792-8.
- Messina M, Wu AH. Perspectives on the soy-breast cancer relation. Am J Clin Nutr. 2009;89:1673S-9S.
- Lamartiniere CA, Zhao YX, Fritz WA. Genistein: mammary cancer chemoprevention, in vivo mechanisms of action, potential for toxicity and bioavailability in rats. J Women’s Cancer. 2000;2:11-9.
This blog sponsored by the Soy Nutrition Institute and the United Soybean Board.