Study investigates the association of soy intake after breast cancer diagnosis with mortality and breast cancer recurrence.
Shu O, Zheng Y, Hui C, et al. Soy food intake and breast cancer survival. JAMA. 2009;302(22):2437-2443.
Longitudinal population-based cohort study
5,042 female breast cancer survivors in China, ages 20 to 75 years, diagnosed between March 2002 and April 2006 and followed through June 2009. Information regarding cancer diagnosis and treatment, lifestyle after cancer diagnosis, and disease progression was collected approximately 6 months post diagnosis. Follow-up assessments were conducted at 18, 36, and 60 months after diagnosis.
To evaluate the association of soy intake after diagnosis of breast cancer with total mortality and breast cancer recurrence
Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence of cancer in a population of women living in China and diagnosed with breast cancer. The inverse association was true for women with either estrogen-receptor (ER)-positive or ER-negative breast cancer, and for women who either took tamoxifen or did not take tamoxifen. In addition, the inverse relationship of soy intake and mortality and recurrence was true for both pre- and postmenopausal women, and for all stages of breast cancer. An inverse relationship was found between treatment with radiation therapy and survival. The use of tamoxifen therapy demonstrated a positive relationship with survival.
Women with a high intake of soy foods were also found to have a higher intake of meat, fish, and cruciferous vegetables; to drink tea; to exercise; and to supplement with vitamins, compared with women who had a lower intake of soy foods. With the exception of a higher consumption of meat, these women maintained behaviors generally associated with a healthy lifestyle.
The relationship of soy foods intake with survival and reduced incidence of recurrence was dose dependent for consumption up to 11 g per day of soy protein (or soy isoflavones up to 40 mg per day). Beyond that, the benefit was lost or reversed.
Women with ER positive breast cancer with the highest consumption of soy had the lowest mortality and recurrence rates, compared with those with the lowest soy intake, whether they took tamoxifen or not.
A number of questions arise in examination of this study. The short duration of the follow-up (4-years) significantly limits a clear understanding of the long-term effects of soy intake on breast cancer survival and recurrence.
The inverse relationship of survival and treatment with radiation therapy brings into question the details of the use of radiotherapy in China. Further investigation into diagnosis and treatment may be helpful in making clear this area of concern.
The inverse relationship of survival and incidence of recurrence with soy intake for both ER positive and ER negative cancers support studies demonstrating additional mechanisms of action beyond estrogenic activity.
The authors point out that soy constituents have been shown to have a multitude of properties that fight cancer, including inhibition of topoisomerases and tyrosine kinases, anti-angiogenesis, anti-inflammatory and antioxidant activity.
The authors point out that soy constituents have been shown to have a multitude of properties that fight cancer, including inhibition of topoisomerases and tyrosine kinases, anti-angiogenesis, anti-inflammatory and antioxidant activity, modulation of sex hormone binding globulin, and enhancing immune response. The study does not address the role of these actions, and the study size limits the exploration of variables such as estrogen-receptor status or greater detail regarding the role of tamoxifen.
The relationship of soy and breast cancer has long been debated, with controversial and inconclusive results. The in vitro and in vivo studies have demonstrated contradictory results regarding the effect of soy on breast cancer cells and on the health of women with breast cancer diagnoses. The recent Life After Cancer Epidemiology (LACE) study examined the effect of soy consumption and breast cancer recurrence among nearly 2,000 women diagnosed with breast cancer living in northern California. The study demonstrated an inverse relationship between breast cancer recurrence in postmenopausal women treated with tamoxifen and consuming the highest intake of soy (comparable to the amount consumed by Asian women), compared to women with the lowest intake of soy. In that study, a decreased incidence of recurrence was found in women consuming soy at the highest level with tumors that were ER-positive or progesterone-receptor (PR)-positive, but not with tumors that were ER or PR negative.1
Another study, conducted in China and published in 2009, showed an inverse relationship between soy consumption and risk of breast cancer but did not address the use of tamoxifen.2 An in vitro study with genestein, published in 2002, suggested an inhibitory effect on tamoxifen.3 The controversies regarding soy and breast cancer are not solved with this current study, but it does give us some additional information. The application of that information, however, is less clear.
The differences in the average amount of soy intake in China and the United States varies significantly (47 mg per day compared to 1–6 mg per day, respectively, of soy isoflavones, as indicated by the authors) and limits the application of this information to the US population. In addition, the differences in the types of soy foods consumed in China (tofu and soy beans) compared to those in the United States (processed soy such as meat substitutes and texturized soy protein in addition to tofu) may also allow for alterations in the benefits of these soy foods.
This study examined only soy food consumption after diagnosis and did not look at soy intake before diagnosis. Another significant difference in soy consumption between China and the United States is the difference in age of exposure to soy foods. One review of the literature exploring the issue of early life intake of genistein suggested consumption of soy during childhood and adolescence reduced the incidence of later breast cancer diagnoses for both pre- and postmenopausal breast cancers.4 Without consideration of these variables, application of the findings in a US population is difficult.
The answer is usually in the big picture. Healthy lifestyle habits, including consumption of a balanced and varied diet rich in cruciferous vegetables, foods high in omega-3 fatty acids, and fiber, along with regular exercise and sleep, are critical. From this study we may consider the addition of some soy foods as helpful for women diagnosed with breast cancer (ER-/PR-positive or -negative) who are pre- or postmenopausal and who are either taking tamoxifen or not taking tamoxifen. Soy supplementation is not addressed in the study and should not be assumed to be equivalent in effect on survival or recurrence. Questions remain regarding the effect of consumption of processed soy foods, and the intake of soy for women who have not had a practice of soy intake early in life.
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1. Guha N, Kwan M, Quesenberry C, Weltzien E, Castillo A, Caan B. 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(2):395-405.
2. Zhang M, Yang H, Holman C. Dietary intake of isoflavones and breast cancer risk by estrogen and progesterone receptor status. Breast Cancer Res Treat. 2009;118(3):553-563.
3. Ju YH, Doerge DR, Alfred KF, Alfred CD, Helferich WG. Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Res. 2002;62;(9):2472-2477.
4. Warri A, Saarinen NM, Makela S, Hilakivi-Clarke L. The role of early life genistein exposures in modifying breast cancer risk. British J Cancer. 2008;98(9):1485-1493.