CLINICAL RESEARCH

The relationship between soy intake and breast cancer risk has been rigorously investigated for more than 20 years.¹ Initial interest in this relationship was based on the low breast cancer incidence rates in soyfood-consuming countries, especially Japan, and rodent data showing that soy inhibits chemically-induced mammary cancer.^2,3 While several putative chemopreventives were identified in soybeans, one class, the isoflavones, has been the focus of most research.

Isoflavones are diphenolic compounds with a very limited distribution in nature (the soybean is the only commonly consumed food to contain nutritionally-relevant amounts).⁴ They exhibit both hormone-dependent and hormone-independent effects under various experimental conditions.^5,6

Although epidemiologic studies generally show that Asian women who frequently consume soyfoods are less likely to report having breast cancer than Asian women who consume relatively little soy, evidence now indicates that to derive protection against this disease, soy must be consumed early in life.^7-9 The hypothesis that early soy intake is protective against breast cancer, which was first proposed in 1995, is consistent with a considerable amount of evidence that early life events in general have a profound impact on the risk of developing breast cancer later in life.^10,11

Despite the low breast cancer rates in soyfood-consuming countries, concern has arisen that the estrogen-like effects of isoflavones, and therefore also soyfoods, could be harmful to breast cancer patients.¹² However, prospective epidemiologic studies from China and the United States not only show soyfoods to be safe for breast cancer patients, but suggest soy consumption improves their prognosis.^13-16

The most recent study to address this issue was conducted by researchers from the Affiliated Hospital of Inner Mongolia Medical College, Hohhot, China.¹⁷ For this study, trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded among the 616 breast cancer patients enrolled in this study. The hazard ratios (hazard ratios are similar to relative risks; a hazard ratio of 1.5 indicates risk was increased by 50% whereas a value of 0.5 means risk was reduced by half) for estrogen receptor (ER) negative (ER-) breast cancer for women in the first through fourth isoflavone intake quartiles were 1.0, 0.83, 0.76 and 0.78, respectively. More pronounced protective effects were noted in response to ER positive (ER+) breast cancer, with hazard ratios for the first through fourth isoflavone intake quartiles being 1.0, 0.77, 0.66 and 0.59, respectively. The reduction in risk was statistically significant for both types of cancers. The cutoffs (mg/d) for the intake quartiles were28.83, respectively. Thus, an intake of approximately one serving of soyfoods per day was associated with a 22 to 41% reduction in mortality.

While the number of participants in this most recent study was relatively small, the results are consistent with two studies conducted in the United States and two from China.^13-16 Further, they are consistent with the 2012 position of the American Cancer Society, which is that “For the breast cancer survivor, current evidence suggests no adverse effects on recurrence or survival from consuming soy and soy foods, and there is the potential for these foods to exert a positive synergistic effect with tamoxifen.¹⁸

<sup>1. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst. 1991; 83: 541-6.
2. Pisani P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer. 2002; 97: 72-81.
3. Barnes S, Grubbs C, Setchell KD, Carlson J. Soybeans inhibit mammary tumors in models of breast cancer. Prog Clin Biol Res. 1990; 347:: 239-53.
4. Franke AA, Custer LJ, Wang W, Shi CY. HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids. Proc Soc Exp Biol Med. 1998; 217: 263-73.
5. Oseni T, Patel R, Pyle J, Jordan VC. Selective estrogen receptor modulators and phytoestrogens. Planta Med. 2008; 74: 1656-65.
6. Li Y, Kong D, Bao B, Ahmad A, Sarkar FH. Induction of cancer cell death by isoflavone: The role of multiple signaling pathways. Nutrients. 2011; 3: 877-896.
7. Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008; 98: 9-14.
8. 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: 792-798.
9. Messina M, Wu AH. Perspectives on the soy-breast cancer relation. Am J Clin Nutr. 2009; 89: 1673S-1679S.
10. Lamartiniere CA, Moore JB, Brown NM, Thompson R, Hardin MJ, Barnes S. Genistein suppresses mammary cancer in rats. Carcinogenesis. 1995; 16: 2833-40.
11. Russo J, Mailo D, Hu YF, Balogh G, Sheriff F, Russo IH. Breast differentiation and its implication in cancer prevention. Clin Cancer Res. 2005; 11: 931s-6s.
12. Helferich WG, Andrade JE, Hoagland MS. Phytoestrogens and breast cancer: a complex story. Inflammopharmacology. 2008; 16: 219-26.
13. Shu XO, Zheng Y, Cai H, Gu K, Chen Z, Zheng W, Lu W. Soy food intake and breast cancer survival. JAMA. 2009; 302: 2437-43.
14. Kang X, Zhang Q, Wang S, Huang X, Jin S. Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy. CMAJ. 2010; 182: 1857-62.
15. Guha N, Kwan ML, Quesenberry CP, Jr., Weltzien EK, Castillo AL, Caan BJ. 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; 118: 395-405.
16. Caan BJ, Natarajan L, Parker B, Gold EB, Thomson C, Newman V, Rock CL, Pu M, Al-Delaimy W, et al. Soy food consumption and breast cancer prognosis. Cancer Epidemiol Biomarkers Prev. 2011; 20: 854-8.
17. Zhang YF, Kang HB, Li BL, Zhang RM. Positive effects of soy isoflavone food on survival of breast cancer patients in china. Asian Pac J Cancer Prev. 2012; 13: 479-82.
18. Rock CLD, C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz ALB, E.V, Hamilton KK, Grant B, McCullough M, Tim Byers T, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer Journal Clinical. 2012.</sup>

According to the American Cancer Society, soy may reduce the risk of certain cancers: “As with other beans or legumes, soy and foods derived from soy are an excellent source of protein and thus provide a good alternative to meat. Soy contains several phytochemicals, and is a rich source of isoflavone phytochemicals, which have weak estrogenic activity and may protect against hormone-dependent cancers. There is growing evidence from epidemiologic studies that the consumption of traditional soy foods such as tofu may decrease the risk of cancers of the breast, prostate, or endometrium, and there is selected evidence for a risk reduction of some other cancers.”

Link to abstract

^{Kushi LH, Doyle C, McCullough M, et al. (2012) American Cancer Society guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 62:30-67.}

A review of 11 studies found a 23% lower risk of lung cancer in those who consumed a higher amount of soy, such as tofu and soymilk, than those who consumed less soy. The authors cautioned the strongest link was in people who never smoked, women, and in Asian populations, and more studies need to be conducted to fully understand the connection between soy and lung cancer.¹

Link to study

^{1. Yang WS, Va P, Wong MY, et al. Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies. Am J Clin Nutr. 2011 Nov. 9 [Epub ahead of print]}

A large meta-analysis of over 16,000 breast cancer survivors showed that eating soyfoods such as soymilk and tofu did not increase the risk of cancer recurrence. While not statistically signficant, a trend was observed toward benefits of soy consumption – women who consumed the most isoflavones (more than 23 mg isoflavones/day, about 1 serving of soymilk), had a 9% reduced risk of mortality and a 15% reduced risk for cancer recurrence.¹

Link to study

^{References:
1.Xiao S et al. Presented at the 102nd Annual Meeting of the American Association for Cancer Research, Orlando, FL, April 2-6, 2011.}

A study by researchers at the National Cancer Institute found that Asian-American women who consumed the most soy between the ages of 5 and 11 were 58% less likely to develop breast cancer in comparison to women who consumed little soy during childhood.¹

Link to study

<sup>References:
1. Korde LA et al. Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol Biomarkers Prev. 2009; Apr 18(4): 1050-9.</sup>

A recent meta-analysis found that in Asian populations, higher soy intake was associated with a 29% decreased risk of breast cancer.¹ However, evidence suggests that this benefit depends on soy consumption early in life.

Link to study

^{References:
1.Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008 Jan 15; 98: 9-14.}

In a recent epidemiological study of nearly 2,000 American breast cancer patients, researchers found that soy isoflavone consumption was associated with an improved prognosis and a reduced risk of cancer recurrence over the six-year follow up period.¹

Link to study

^{References: 1. Guha N 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; 118: 395-405.}