The Effects of Pulsed Alcohol Consumption on Mouse Mammary Tumorigenesis

Alcohol has been implicated as the only dietary factor that increases the risk of breast cancer in women. It is not known whether the effects of alcohol exposure are the same throughout the lifetime, or if alcohol exerts a greater effect at times of rapid remodeling of breast tissue, such as puberty or post-lactational involution, compared to a resting adult state. The purpose of this study is to define the effects of short term pulsing with ethanol on subsequent tumor development and metastasis in resting, nonparous mice. These resting mice serve as age-matched controls for a larger study comparing ethanol’s effects on parous mice when administered during post-lactational involution. For this project, transgenic FVB-MMTV- HER2/neu mice, which overexpress the epidermal growth factor receptor type 2 in the mammary gland, are used to model the etiology of HER2-overexpressing human breast cancers. Nonparous female mice, aged 70-85 days, were administered 0, 0.5%, 1%, or 2% alcohol in liquid diets for a 2 week period, and then evaluated for tumorigenesis over the following 9 months. No significant difference is observed between control or alcohol-fed mice in terms of tumor latency, multiplicity, burden, or growth rate. Alcohol feeding likewise has no effect on frequency of lung metastases. However, nonparous mice show an increased latency compared to parous mice, confirming that parity accelerates tumorigenesis. These results show that alcohol consumption for short time periods has no effect on HER2-mediated mammary tumorigenesis in the nonparous mouse