Abstract 4248: A high-fat diet induces an inflammatory tumor microenvironment in MNU-induced estrogen receptor positive mammary tumors

Abstract

Abstract The link between obesity and breast cancer has received much attention because it is associated with an increased risk of breast cancer, an increased incidence of recurrence, higher death rates, and reduced sensitivity to anti-hormonal therapy in post-menopausal women. In addition, obesity is associated with a chronic, low grade inflammatory status. Surprisingly, obesity can have different effects in pre-menopausal women where patient outcome is actually better in obese than lean women. This study was conducted to create an animal model to examine the effects of high-fat (HF) diet on estrogen-dependent mammary tumors in cycling rats. Sprague-Dawley rats were injected with N-Methyl-N-Nitrosourea (MNU) at 6 weeks of age to induce mammary tumors. The next day they received HF diet (45% kcal from fat) or normal fat (NF) diet (10% fat) (n=6-7) and animals were kept on these diets for an average of 15 weeks. Ninety-six percent of rats developed mammary tumors and all the tumors were ER positive. The tumor volume, tumor weight and tumor growth rate were not different between the HF or NF diet groups. Also, the HF diet did not influence the body weight, liver weight and adipose mass weight. However, the expression of pro-inflammatory cytokines, such as TNFa and IL-1b, was significantly up-regulated in tumors of the HF diet group compared to control. Macrophage infiltration was also increased in the tumors of the HF diet group. There was also a tendency of increased NFkB DNA binding activity in the HF diet group. Moreover, macrophage infiltration was significantly correlated with the amount of proinflammatory cytokine gene expression in the HF but not the NF diet group. In agreement with clinical data, cycling rats on the HF diet responded better to tamoxifen than did rats on the NF diet, with a greater reduction in tumor size over 20 days of treatment. Taken together, these results indicate that a HF diet induces a pro-inflammatory tumor microenvironment without causing obesity in cycling rats and that these tumors may be more responsive to endocrine therapy. Our findings also provide a model for future studies into the mechanism by which high fat diet may affect tumor growth and response to therapy in premenopausal women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4248. doi:1538-7445.AM2012-4248