Phytoestrogens (Plant Estrogens)
CATEGORY*: Endocrine disruptor
USED IN: Naturally occurring in whole grains, dried beans, peas, fruits, broccoli, cauliflower, soy; also as concentrated extracts from these foods
THE GIST: There is conflicting research on the health effects of soy-based diets. In general, the current human research indicates that soy foods have protective effects against breast cancer in women.
State of the Evidence on Phytoestrogens (Plant Estrogens)
The prevailing evidence against synthetic estrogens must be understood alongside evidence about the effects of plant estrogens (phytoestrogens). Foods such as whole grains, dried beans, peas, fruits, broccoli, cauliflower and especially soy products are rich in phytoestrogens. Although scientific evidence suggests that plant-based estrogens offer nutritional benefits and are associated with healthy diets (Cederroth, 2009), the data are conflicting as to whether soy-based diets are beneficial, harmful or neutral in their effects on breast cancer risk (Andres, 2011; Rice, 2006).
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Some of the disparity in the literature may be related to type of soy products or other phytoestrogen-containing vegetables consumed by individuals. For example, although two natural phytoestrogens found in soy — genistein and its metabolite genistin (both referred to as isoflavones because of their chemical structure) — have been shown to increase breast tumor growth in a number of different models, highly processed soy flour that does not contain isoflavones has no effect. Purified soy protein isolates are often processed to contain different concentrations of isoflavones, and their influence on mammary tumors is related to the amount of isoflavone, not the total amount of soy protein consumed (Helfrich, 2008).
Several epidemiological studies have shown that regular consumption of soy-based products, or other vegetables high in phytoestrogens, as part of a normal balanced diet can exert a protective influence against later development of breast cancer. This effect has been studied extensively in China, where soy intake is a regular part of the cultural diet. There, substantial evidence indicates that higher soy intake in adulthood or in adolescence is associated with a decreased risk of pre-menopausal breast cancer (Lee, 2009). Other studies have found protective effects of soy intake for both pre- and post-menopausal cancer, independent of the tumors’ receptor profile (estrogen-receptor and progesterone-receptor positive or negative) (Zhang, 2009). On the other hand, in a prospective study of women aged 43 to 55 years who had never been diagnosed with breast cancer but were considered to be at high risk, six months of dietary isoflavone (PTIG-2535, containing 150 mg genistein, 74 mg daidzein, and 11 mg glycitein )intake was associated with increased proliferation of breast cells. The effect was most pronounced in pre-menopausal women (Khan, 2012a).
For Chinese women who were previously diagnosed with breast cancer, consumption of soy in its many forms found regularly in a woman’s diet was correlated with decreased recurrence of cancer and longer survival (Shu, 2009). Complicating the picture further is a study of Korean women who had previously been diagnosed and treated for breast cancer. Dietary soy intake was associated with a decreased rate of recurrence in women whose cancers were HER-2 negative, and an increased rate of recurrence of cancer in women whose original tumors were HER-2 positive (Woo, 2012).
A study of Asian-American women living in California and Hawaii found that soy intake during childhood, adolescence and adulthood was associated in all three cases with decreased later risk of breast cancer (Korde, 2009). The protective effect of regular dietary soy intake during childhood was the strongest, and it was not mitigated when other variables such as site of birth (Asian countries or United States), degree of continuing Asian lifestyle and cultural practices, reproductive factors, or family history of breast cancer were factored into the analysis. A recent meta-analysis that combined data from six studies found that regular dietary intake of soy during adolescence decreased the incidence of all later breast cancers and was particularly effective in decreasing cancer incidence in pre-menopausal women. There was no reported difference in the effects of dietary intakes of soy during adolescence between Asian and American/European women (Zhao, 2012). In general, protective effects of dietary soy intake have been found to be strongest in association with childhood and early adolescent intake (Aldercruz 2003). One possible explanation for this association is that exposures to genistein and other phytoestrogens around the time of puberty may mimic the protective changes in breast development that are usually observed during the first pregnancy (Messina, 2009; Warri, 2008).
Studies examining non-soy phytoestrogen intake and breast cancer risk in non-Asian populations have found more mixed results (Wu, 2008). This may be related to the difference in both amounts and types of phytoestrogens typically eaten as part of the traditional diets found in the United States and in Europe (Mense, 2008). As examples, a French study found that consuming non-soy phytoestrogens as part of a woman’s daily diet had a protective effect against post-menopausal breast cancer (Touillaud, 2007), yet a British study found no such relationship (Travis, 2008). And a multiethnic study conducted in Hawaii demonstrated that the amount of soy in the diet might change the relationship between other phytoestrogens and breast cancer risk. For Japanese Americans who had high soy content in their regular diets, there was a strong and statistically significant relationship with non-soy-based phytoestrogens and decreased risk of breast cancer. This was not the case for white women in the study, who tended to eat diets lower in soy content (Goodman, 2009).
Data from studies on laboratory animals and cell culture models have also indicated a complicated story. In several studies, exposures to phytoestrogens led to increases in mammary tumor proliferation and growth. Genistein and daidzein (another soy phytoestrogen), as well as their metabolites, cause oxidative DNA damage, a process that is thought to play a role in tumor initiation (Murata, 2004). Along with many other plant-based phytoestrogens and other compounds, genistein alters the expression of many genes involved in cell proliferation and tumor suppression through epigenetic mechanisms (Khan, 2012b).
The effects of the phytoestrogens may well be related to the particular mixtures of components in the diet (Dip, 2009), and cellular effects may vary depending on concentration and timing (Andres, 2012). One study examined the effects of different types and concentrations of phytoestrogens on the expression of estrogen-dependent gene activity in human breast cancer cells grown in vitro (MCF-7 cells). Low doses of genistein resulted in a pattern of expression that indicated increased cell proliferation, whereas somewhat higher concentrations led to increased apoptosis, or cell death. The phytoestrogen daidzein (also found in soy) slightly enhanced cell proliferation in the absence of natural estrogen (a possible model for post-menopausal breast cancer), whereas resveratrol (a phytoestrogen found in grapes and red wine) resulted in a statistically significant decrease in tumor cell proliferation (Sakamoto, 2009). These latter data are consistent with other studies finding anti-carcinogenic effects of resveratol in several models (Athar, 2009; Garvin, 2006).
Laboratory data suggest that the two soy-based phytoestrogens, genistein and daidzein, may have opposing effects on the efficacy of adjuvant hormone-based treatments for breast cancer. In cell culture and animal models, genistein may interfere with the anti-cancer effects of both tamoxifen (Du, 2012; Liu, 2005) and aromatase inhibitors (van Duursen, 2011); daidzein, on the other hand, may enhance tamoxifen’s efficacy (Constantinou, 2005). Epidemiological data suggest that dietary soy isoflavone intake, especially daidzein intake, may be associated with reduced recurrence of cancer in tamoxifen-treated women (Caan, 2011; Guha, 2009).
Recently concern has been raised about exposure of newborn babies to soy-based products, primarily through infant formulas. Although one study has shown that feeding only soy formula for the first four months of life was associated with a decrease in later development of breast cancer (Boucher, 2008), animal studies have indicated deleterious effects of neonatal soy exposure on development of the female reproductive system and subsequent fertility (Jefferson, 2009).
In summary, while animal and human data seem contradictory, overall, current epidemiologic evidence from studies in humans suggests that eating soy products and other phytoestrogens during the adolescent period has a protective effect against subsequent breast cancer risk. Evidence regarding the potential beneficial vs. deleterious effects in women living with breast cancers of various subtypes is not conclusive and needs further study.
*For chemicals that have been shown to be carcinogens, we provide classifications from two authoritative bodies: the International Agency for Research on Cancer (IARC, an international body) and the National Toxicology Program (NTP, a division of the U.S. Department of Health and Human Services). We have categorized endocrine-disrupting compounds where the body of peer-reviewed research indicates a strong foundation for doing so.