Academic journal article Environmental Health Perspectives

Phytoestrogens and Breast Cancer Prevention: Possible Mechanisms of Action

Academic journal article Environmental Health Perspectives

Phytoestrogens and Breast Cancer Prevention: Possible Mechanisms of Action

Article excerpt

Breast cancer is an important public health problem worldwide. In the United States, breast cancer represents the most common neoplasm and the second most frequent cause of cancer death in women (American Cancer Society 2006). Steroidal estrogens have been implicated in the etiology of breast cancer and have been added to the list of known human carcinogens [International Agency for Research on Cancer (IARC) 1999, 1987; National Toxicology Program (NTP) 2002]. Estrogens are suggested to cause breast cancer by stimulating cell growth and proliferation through receptor-mediated processes and via their genotoxic metabolites (Cavalieri et al. 2006; Yager and Davidson 2006). Phytoestrogens are a class of plant-derived compounds that are structurally similar to mammalian estrogens (Sirtori et al. 2005). Ecologic observations indicate that the incidence of breast cancer is much lower in Asian women, who consume significantly higher amounts of phytoestrogens than Western women (Adlercreutz 2002). Second- and third-generation descendants of women who migrated to Western countries from Asia have breast cancer risks similar to those of women in the host country, suggesting that lifestyle and not genetic factors explain the low breast cancer risk observed in Asian women (Probst-Hensch et al. 2000; Usui 2006). However, despite recent attention related to the putative chemoprotective properties of phytoestrogens, epidemiologic studies have produced inconsistent results, and the relationship between phytoestrogens and breast cancer remains enigmatic (Gikas and Mokbel 2005; Messina et al. 2006; Peeters et al. 2003; Trock et al. 2006). Moreover, the possible mechanisms of phytoestrogen action in breast cancer have yet to be resolved.

Phytoestrogen Classification

Phytoestrogens are biologically active phenolic compounds of plant origin that structurally mimic the principal mammalian estrogen 17[beta]-estradiol ([E.sub.2]; Figure 1) (Sirtori et al. 2005). Shared structures include a pair of hydroxyl groups and a phenolic ring, which is required for binding to estrogen receptors (ER)-[alpha] and ER-[beta], and the position of these hydroxyl groups appears to be an important factor in determining their abilities to bind the ERs and activate transcription (Le Bail et al. 2000). Four main classes of compounds are currently recognized as phytoestrogens--the isoflavones, stilbenes, coumestans, and lignans (Moon et al. 2006; Sirtori et al. 2005). These types of phytochemicals are some of the most prevalent compounds found in fruits, vegetables, legumes, and tea and are generally concentrated in the fruit skin, bark, and flowers of plants (Moon et al. 2006). Resveratrol, daidzein, quercetin, and genistein represent four of the most commonly ingested and most intensely studied phytoestrogens (Figure 1).

In East and Southeast Asia, the average daily intake of phytoestrogens is estimated to be between 20 and 50 mg (Adlercreutz 1998; Sirtori et al. 2005). In contrast, the typical diet of an adult in the United States contains only 0.15-3 mg phytoestrogens per day, and in Europe the average daily phytoestrogen consumption is estimated to be even lower, falling between 0.49 and 1 mg (Adlercreutz 1998; Sirtori et al. 2005). According to various epidemiologic studies, plasma isoflavone concentrations range from 2 [micro]M (Japanese men) to 5 nM (Finnish study subjects); however, local tissue phytoestrogen concentrations are suggested to be 2-3 times higher than plasma levels (Adlercreutz et al. 1993; Arai et al. 2000; Morton et al. 2002; Uehar et al. 2000).

Phytoestrogens and Breast Cancer Risk

The importance of estrogens in the etiology of breast cancer is widely recognized (Bhat et al. 2003; Cavalieri et al. 2006; Yager and Davidson 2006). Estrogens have been implicated in the initiation and promotion stages of breast cancer, and lifetime estrogen exposure is a major risk factor for breast cancer development (Yager and Davidson 2006). …

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