Effect of soy isoflavones on the growth of human breast tumors: findings from preclinical studies.

Youngjoo Kwon

doi:10.1002/fsn3.142

Abstract

Breast cancer is the most common cancer among women worldwide, and many women with breast cancer live more than 5 years after their diagnosis. Breast cancer patients and survivors have a greater interest in taking soy foods and isoflavone supplements. However, the effect of isoflavones on breast cancer remains controversial. Thus, it is critical to determine if and when isoflavones are beneficial or detrimental to breast cancer patients. According to the available preclinical data, high concentrations of isoflavones inhibit the proliferation of breast cancer cells, regardless of their estrogen receptor (ER) status. In comparison, genistein, a major isoflavone, has stimulated tumor growth at low concentrations and mitigated tamoxifen efficacy in ER-positive breast cancer. Studies have indicated that the relative levels of genistein and estrogen at the target site are important to determine the genistein effect on the ER-positive tumor growth. However, studies using ovariectomized mice and subcutaneous xenograft models might not truly reflect estrogen concentrations in human breast tumors. Moreover, it may be an oversimplification that isoflavones stimulate hormone-dependent tumor growth due to their potential estrogenic effect since studies also suggest nonestrogenic anticancer effects of isoflavones and ER-independent anticancer activity of tamoxifen. Therefore, the concentrations of isoflavones and estrogen in human breast tumors should be considered better in future preclinical studies and the parameters that can estimate those levels in breast tumors are required in human clinical/epidemiological investigation. In addition, it will be important to identify the molecular mechanisms that either inhibit or promote the growth of breast cancer cells by soy isoflavones, and use those molecules to evaluate the relevance of the preclinical findings to the human disease and to predict the health effects of isoflavones in human breast tumors.

Highlights

High concentrations of genistein (at a 50 or 100 lmol/L level) inhibited the proliferation of human breast cancer cells, including estrogen receptor (ER)-positive MCF-7 cell line (Peterson and Barnes 1991, 1996; Pagliacci et al 1994; Chen et al 2003)
Food Science & Nutrition published by Wiley Periodicals, Inc
Based on available preclinical data, the high concentration of genistein and equol, which might be difficult to be achieved in human breast tissues or tumors, effectively inhibited the growth of breast cancer cells regardless of their estrogen receptor (ER) status

Summary

Introduction

High concentrations of genistein (at a 50 or 100 lmol/L level) inhibited the proliferation of human breast cancer cells, including ER-positive MCF-7 cell line (Peterson and Barnes 1991, 1996; Pagliacci et al 1994; Chen et al 2003). A high concentration of genistein (>25 lmol/L) inhibits the growth of ER-positive breast cancer cells in vitro through both ER-dependent and -independent mechanisms. More detailed molecular mechanisms than the estrogen agonist effect will provide a better rationale for the inhibition of soy intake in breast cancer patients or women at high risk for breast cancer.

Results

Conclusion