Abstract 904: Lifetime genistein alters mammary tumors’ response to anti-estrogen tamoxifen treatment by affecting immune function in rats

Abstract

Abstract Consistent with the human data showing that soy intake reduces the risk of breast cancer recurrence, we have previously reported that childhood and lifelong genistein (GEN) intake enhanced response of mammary tumors to tamoxifen (TAM) treatment and prevented recurrence in rats. Mammary tumor recurrence was also inhibited by starting GEN consumption in adulthood. Since GEN is shown to alter immune functions, and tumor immune responses can determine cancer outcome, we examined several immune markers in the tumor prior to TAM treatment. Female Sprague-Dawley rats were fed control AIN93G diet or AIN93G diet supplemented with 500 ppm GEN either during childhood (between postnatal days 15 and 30), adulthood (from 55 days to end of the study), or both. Mammary tumors were induced by DMBA at the age of 48 days, and when a tumor reached a size of 1.4 cm in diameter (criteria for starting TAM treatment in the previous study), rats were euthanized (n = 15 per group), and blood and mammary tumors were collected. We determined the expression of CD8-alpha (present in cytotoxic T lymphocytes) and Foxp3, TGFβ1 and TGF2 (present in regulatory T-cells, Treg) in mammary tumors from rats with varying lifetime exposures to GEN. Compared with the control rats, expression of CD8-alpha mRNA was significantly increased by GEN intake at any time during the life cycle, suggesting an elevation in cytotoxic T-cells density infiltrating the tumor. Foxp3 and TGF-β1 mRNA were significantly reduced by GEN consumption. Increased Treg levels in tumors result in the suppression of immune responses; therefore, a reduction in Foxp3 and TGF-β1 may indicate a decrease in immune suppression. TGF-2 mRNA expression was significantly increased in the tumors of rats that consumed GEN only as adults. In the serum, interleukin (IL)-1 and IL-6 levels were significantly elevated in rats that consumed GEN only during childhood, whilst IL-6 was reduced in rats consuming GEN during lifetime or only as adults. IL-12 that is reported to stimulate cellular immunity, was increased in the rats that consumed GEN during lifetime or as adults. Our findings suggest that the ability of GEN intake to prevent mammary cancer recurrence is associated with improved immune responses in the tumor. Citation Format: Xiyuan Zhang, Katherine Cook, Leena Hilakivi-Clarke. Lifetime genistein alters mammary tumors’ response to anti-estrogen tamoxifen treatment by affecting immune function in rats. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 904. doi:10.1158/1538-7445.AM2015-904