Transforming growth factors-beta are not good biomarkers of chemopreventive efficacy in a preclinical breast cancer model system

Using a carcinogen-initiated rat model of mammary tumorigenesis, we tested the hypothesis that transforming growth factor (TGF)-betas are useful bioma rkers of chemopreventive efficacy in the breast. The chemopreventive agents tested were tamoxifen and the retinoids 9-cis-retinoic acid (9cRA) and N-( 4-hydroxyphenyl) retinamide (4-HPR), because both antiestrogens and retinoi ds have previously been shown to upregulate TGF-betas in vitro. Despite dem onstrable chemopreventive efficacy in this model, none of these agents, alo ne or in combination, had any significant impact on the expression of TGF-b etas in the mammary ductal epithelium or periductal stroma as determined by immunohistochemistry. These data suggest that TGF-betas are not likely to be useful biomarkers of chemopreventive efficacy in a clinical setting.