Is soy consumption good or bad for the breast?

Abstract

Genistein in soy activates estrogen receptor (ER)-α and ERβ and acts as an estradiol in multiple target tissues. Because estrogens increase breast cancer risk and genistein promotes the growth of ER-positive human breast cancer cells, it has remained unclear whether this isoflavone or soy is safe. Results reviewed here suggest that women consuming moderate amounts of soy throughout their life have lower breast cancer risk than women who do not consume soy; however, this protective effect may originate from soy intake early in life. We also review the literature regarding potential risks genistein poses for breast cancer survivors. Findings obtained in 2 recent human studies show that a moderate consumption of diet containing this isoflavone does not increase the risk of breast cancer recurrence in Western women, and Asian breast cancer survivors exhibit better prognosis if they continue consuming a soy diet. The mechanisms explaining the breast cancer risk-reducing effect of early soy intake or the protective effect in Asian breast cancer survivors remain to be established. We propose that the reduction in risk involves epigenetic changes that result in alterations in the expression of genes that regulate mammary epithelial cell fate, i.e. cell proliferation and differentiation. Lifetime soy consumption at a moderate level may prevent breast cancer recurrence through mechanisms that change the biology of tumors; e.g. women who consumed soy during childhood develop breast cancers that express significantly reduced Human epidermal growth factor receptor 2 levels. More research is needed to understand why soy intake during early life may both reduce breast cancer risk and risk of recurrence.

FIGURE 1

Equivalent amounts of dietary genistin and genistein (750 μg/g) stimulate growth of estrogen-dependent breast cancer tumors MCF-7 in athymic mice. Cells (1.5 × 10⁵ MCF-7 cells/site) were injected subcutaneously into dorsal flanks of ovariectomized athymic mice. After tumor establishment (40 mm²), E2 pellets were removed and mice were randomly assigned to 4 treatment groups. Positive control (+E2) mice were reimplanted with a new E2 pellet and along with negative controls (−E2) were fed an AIN 93G diet alone. For phytoestrogen groups, mice consumed either dietary genistin (1200 μg/g) or genistein (750 μg/g) mixed with AIN 93G. Tumors were monitored weekly and tumor size was calculated and is expressed as mean cross sectional area (mm²) of all tumors in each treatment group ± SEM. Data from wk 11 of treatment is presented. Figure reproduced with permission from (41).

FIGURE 2

Food matrix modulates the estrogenic effects of equivalent amounts of genistein aglycone (750 μg/g) on estrogen-dependent MCF-7 tumor growth in athymic mice. Cells were injected subcutaneously into dorsal flanks of ovariectomized athymic mice. After tumor establishment, E2 pellets were removed and mice were randomly assigned to treatment groups. Positive control (PC) mice were reimplanted with a new E2 pellet. Both the negative control (NC) and PC mice were fed a low-phytoestrogen control diet (AIN-93G). Treatment groups also included an AIN-93G diet with genistein (GI), mixed isoflavones (MI), Novasoy (NS), molasses (MOL), and soy flour + mixed isoflavones (SF + MI). Tumors were monitored weekly and tumor size was calculated and is expressed as mean cross sectional area (mm²) of all tumors in each treatment group ± SEM. Data from wk 11 of treatment is presented. Figure reproduced with permission from (43).

FIGURE 3

Risk of recurrence of breast cancer by soy intake, assessed using FFQ, among 1954 Western breast cancer survivors (101) (A) and 5042 Chinese breast cancer survivors (102) (B). Relative risk (RR) and 95% CI are shown for glycitein, genistein, and daidzein intake in A and for isoflavone and soy protein intake in B. The study done in Western women showed no protective effect and an almost significantly increased risk of recurrence among those not taking tamoxifen and having the highest intake of genistein and daidzein. In contrast, the study done in Chinese women found a significantly reduced risk of recurrence in women having the highest level of isoflavones and soy protein in their diet. Reproduced with permission.