Abstract 1812: Effects of vitamin D on obesity-induced increase in ER-positive and ER-negative mammary cancer in mice

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL We have previously found that dietary exposure to vitamin D (VD3) reverses the increase in endometrial cancer in obese Pten+/- mice. Since obesity also increases breast cancer risk and recurrence, this study investigated whether VD3 supplementation may inhibit development of mammary cancer in obese mice. As the protective effect of VD3 in the endometrium was not related to the estrogen receptor (ER), we pursued another potential pathway and determined whether VD3 reverses obesity-induced insulin resistance. Methods: Two mouse models were used: DMBA-treated C57BL/6 mice developing ER positive (ER+) mammary tumors, and Pten+/- mice which develop triple negative mammary tumors. C57BL/6 mice were wild type littermates of the Pten+/- mice. Mice in the two models were divided into four groups after weaning, and they were fed (a) AIN93G based control diet, (b) diet supplemented with 20K IU VD3, (c) obesity-inducing diet (OID), or (d) OID supplemented with 25K IU VD3. Results: OID induced insulin resistance and increased mammary tumorigenesis in both C57BL/6 and Pten+/- mice. VD3 significantly inhibited ER+ (p<0.05) and ER- (p<0.04) mammary cancer, but did not reverse the obesity-induced increase in cancer risk. Results obtained in the insulin tolerance test, however, indicated that VD3 prevented the development of insulin resistance in the OID fed obese C57BL/6 and Pten+/- mice. Conclusions: Dietary exposure to VD3 protects against development of ER+ and triple negative mammary cancer, but only in lean mice. VD3 supplementation also prevents insulin resistance in obese mice, but this is not sufficient to reduce mammary cancer risk in either C57BL/6 or Pten+/- mice Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1812. doi:10.1158/1538-7445.AM2011-1812