The Effects of a High-Fat Diet on Mammary Gland Biology in a Model of Triple-Negative Breast Cancer

Breast cancer is still the leading cause of death for women in the US. Triple-negative breast cancer (TNBC), which has been correlated with obesity in both pre and post-menopausal women, makes up only 10-20% of breast cancer cases but offers a poorer prognosis and lack of response to treatment. Diets high in fat plays a large role in the increase in obesity we therefore hypothesize that diets high in fat play a role in tumor development and progression due to changes in mammary gland microenvironment. More specifically, we hypothesize that changes in mammary adipose tissue (MAT) result in different more pro-tumorigenic secreted factors being released from the MAT and negatively affect the adjacent epithelial cells. HF feeding resulted in minimal changes in body weight but did increase fasting blood glucose as expected, pointing to the mice having become insulin resistant. MRI images of the inguinal mammary glands of mice fed HFD, additionally showed denser parenchyma compared to control-fed counterparts. H&E staining of the inguinal mammary glands demonstrated much higher adipocyte content and more active glands with HFD. Increases in secreted factors due to HFD, such as pentraxin 3, IL-6, and LPA, which have all been associated with poorer prognosis in TNBC, make the mammary microenvironment more invasive as which saw with the increase in poorly differentiated tumors with HF feeding at 20-21 weeks. These data suggest that the changes to the mammary adipose tissue due to high animal fat consumption not only leads to a more carcinogenic environment but also results in poorly-differentiated and higher grade tumors. This suggests that diets low in animal fat may be an effective treatment for TNBC but that inhibiting proteins pentraxin 3, like may also be an effective treatment for TNBC.