Soy and Breast Cancer

-Dr. Nicholas LeRoy, DC, MS

There has been considerable investigation of the potential for soy foods to reduce risk of cancer, particularly cancer of the breast. This interest dates back more than two decades and in 1990, participants of a workshop sponsored by the U.S. National Cancer Institute concluded that soybeans contain several chemopreventive agents [1]. The basis for the initial investigation into a potential relationship between soy and breast cancer was based largely on the observation that women in Asia with their high consumption of soybeans had a considerably lower incidence of breast cancer than their western counterparts.

In the last two decades, epidemiologic research (i.e. research focusing on large populations of persons in a specific geographic area) has verified the suspicion that there exists an inverse relationship between soy consumption and breast cancer incidence [2,3,4]. In other words, the more soy a woman eats the lower her risk of breast cancer.

In recent years, however, the relationship between soy and breast cancer has become controversial, largely due to an attempt to study the effects of isolated soy food chemicals. These chemicals, known as isoflavones, exhibit estrogen-like properties under certain experimental conditions, and may stimulate the growth of existing estrogen-sensitive breast tumors [5]. For the purpose of clarification, controversy has resulted only when researchers began isolating singular chemicals found in soy and using these chemicals individually and at very high concentrations—in other words, like drugs. Author's note: I blame this confusion on the misguided pursuit of western researchers' "magic bullet" mentality. That is, a preoccupation with finding a pill to treat everything that ails humans despite the fact that there has never been found a magic bullet despite enormous money and resources invested to this ill-conceived pursuit. "Ill-conceived" because it ignores the fundamental apothegm that diet and lifestyle are the most important modifiable factors that relate to all disease.

The issue of soy or no soy gets even more confounding when studying the effects--again of singular isoflavones—on women taking tamoxifen as part of breast cancer treatment or prevention. Two of the three soy isoflavones are genistein and daidzein. One study published in 2005 found that genistein was able to negate the positive effect of tamoxifen, while a combination of daidzein and tamoxifen produced increased protection against breast cancer [6]. A study published in 2008 likewise found that genistein can interfere with tamoxifen activity [7]. These two studies refuted the findings of a 2002 publication that showed that genistein increased the effectiveness of tamoxifen [8]. Needles to say, everyone was confused by these contradictory findings and cancer researchers concluded there was sufficient evidence to advise women to refrain from isoflavone supplementation. It is important to reiterate these warnings were for supplementation with isoflavones—not for soy as part of a healthy diet. It must also be noted that in using soy isoflavones as drugs, the levels of genistein and daidzein were at doses 5-20 times that which is normally consumed by humans. Fortunately, a large, population-based cohort study of 5042 female breast cancer survivors in China is providing the clarification sought by many women regarding this important topic.

The Shanghai Breast Cancer Survival Study included women who were diagnosed between 2002 and 2006 and followed-up until 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews. I've presented the results as direct quotes from the study followed by my comments:

  • "Soy food consumption after cancer diagnosis, measured as soy protein intake, was inversely associated with mortality and recurrence. The association of soy protein/isoflavone intake with mortality and recurrence appear to follow a linear dose-response pattern until soy protein intake reaches 11 grams a day (or soy isoflavone intake reaches 40 mg a day). After these points, the association appears to level off or even rebound." COMMENT: This reiterates what we had already known, that is, soy as part of a diet decreases the recurrence of breast cancer and death from breast cancer. It also indicates more is not necessarily better. Reasonable amounts of dietary soy for women diagnosed with breast cancer are a good thing.
  • "In our study, we found that soy food intake was associated with improved survival regardless of tamoxifen use, while tamoxifen use was related to improved survival only among women who have low or moderate levels of soy food intake. Tamoxifen was not related to further improvement of survival rates among women who had the highest level of soy food intake. More importantly, women who had the highest level of soy food intake and who did not take tamoxifen had a lower risk of mortality and a lower risk of recurrence rate than women who had the lowest level of soy food intake and used tamoxifen, suggesting that high soy food intake and tamoxifen may have a comparable effect on breast cancer outcome." COMMENT: This puts to rest the issue of whether or not women on tamoxifen should eat soy. They should. In fact, this research suggests that women with breast cancer may be able to use high soy food intake instead of tamoxifen.
  • "In our comprehensive evaluation of soy food consumption and breast cancer outcome using data from a large, population-based cohort study, we found that soy food intake was inversely associated with mortality and recurrence. The inverse association did not appear to vary by menopausal status and was evident for women with ER-positive and ER-negative cancers and early and late-stage cancers." COMMENT: This is big news. Soy helped across the board—early to late stage of the disease, pre- or post-menopausal status, and both receptor positive and negative classes. Until opponents of soy produce contradictory results in human population research, the dangerous advice for women with breast cancer is to avoid soy.
  • "In summary, in this population-based prospective study, we found that soy food intake is safe and were associated with lower mortality and recurrence among breast cancer patients. The association of soy food intake with mortality and recurrence appears to follow a linear dose-response pattern until soy food intake reaches 11 grams a day of soy protein; no additional benefits on mortality and recurrence were observed with higher intakes of soy food."

In conclusion, women should include soy as part of their diets, but be hesitant to use soy isoflavone supplements. This includes women with and without breast cancer, who are both pre- and post-menopausal, who are taking tamoxifen, and those women with breast cancer that is ER-negative or ER-positive. This conclusion is based on the fact that all human research to date has confirmed these recommendations and not one single human trial have refuted it.

References:

  1. Messina M, Barnes S: The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991, 83:541-546.
  2. Trock BJ, Hilakivi-Clarke L, Clarke R: Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 2006, 98(7):459-71.
  3. Wu AH, Yu MC, Tseng CC, Pike MC: Epidemiology of soy exposures and breast cancer risk. Br J Cancer 2008, 98(1):9-14.
  4. Lee SA, Shu XO, Li H, Yang G, et al: Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women's Health Study. Am J Clin Nutr 2009, 89(6):1920-6.
  5. Messina MJ, Loprinzi CL: Soy for breast cancer survivors: a critical review of the literature. J Nutr 2001, 131:30955-1085.
  6. Constantinou AI, White BE, Tonetti D, et al: The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumours. Eur J Cancer 2005, 41(4):647-54.
  7. Helferich WG, Andrade JE, Hoagland MS: Phytoestrogens and breast cancer: a complex story. Inflammopharmacology 2008, 16(5):219-26.
  8. Tanos V, Brzezinski A, Drize O, et al: Synergistic inhibitory effects of genistein and tamoxifen on human dysplastic and malignant epithelial breast cells in vitro. Eur J Obstet Gynecol Reprod Biol 2002, 102(2):188-94.