Phytoestrogens and Breast Cancer Prevention: Possible Mechanisms of Action

Sarah M. Mense; Tom K. Hei; Ramesh K. Ganju; Hari K. Bhat


Environ Health Perspect. 2008;116(4):426-433. 

In This Article

Abstract and Introduction

Objective: Phytoestrogens display an array of pharmacologic properties, and in recent years investigation of their potential as anticancer agents has increased dramatically. In this article we review the published literature related to phytoestrogens and breast cancer as well as suggest the possible mechanisms that may underlie the relationship between phytoestrogens and breast cancer.
Data sources: Electronic searches on phytoestrogens and breast cancer were performed on MEDLINE and EMBASE in June 2007. No date restriction was placed on the electronic search.
Data extraction: We focused on experimental data from published studies that examined the characteristics of phytoestrogens using in vivo or in vitro models. We also include human intervention studies in this review.
Data synthesis: We evaluated evidence regarding the possible mechanisms of phytoestrogen action. Discussions of these mechanisms were organized into those activities related to the estrogen receptor, cell growth and proliferation, tumor development, signaling pathways, and estrogen-metabolizing enzymes.
Conclusions: We suggest that despite numerous investigations, the mechanisms of phytoestrogen action in breast cancer have yet to be elucidated. It remains uncertain whether these plant compounds are chemoprotective or whether they may produce adverse outcomes related to breast carcinogenesis.

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.


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