A new study has reported that alcohol consumption promotes premenopausal HER2 overexpressing (HER2+) breast cancer development in a mouse model of HER2+ breast cancer. Alcohol consumption is known to increase the risk of breast cancer. However, alcohol's mechanism of action in promoting breast cancer remains unclear.
A large reduction in estrogen levels takes place during the transition to postmenopausal status as ovarian estrogen production drops. It has not been determined whether the risk of breast cancer attributable to alcohol consumption is influenced by the different levels of estrogen found in premenopausal and postmenopausal women.
Mouse mammary tumor virus neu transgenic mice (MMTV-neu mice) that overexpress human epidermal growth factor receptor 2 (HER2/neu) were used as a breast cancer model in the study. These mice spontaneously develop estrogen receptor negative HER2+ mammary tumors. The mammary tumorigenesis process in MMTV-neu mice resembles that of patients with HER2+ breast cancer. The mice were divided into two groups: nonovariectomized mice (intact and functioning ovaries) and ovariectomized (ovaries surgically removed to model postmenopausal status).
The mice were further subdivided into groups that received either 0% (control), 5%, or 20% alcohol (ethanol) in their drinking water. Mammary tumor development and progression were measured, in addition to the effects of alcohol on estrogen availability and signaling.
Exposure to 20% alcohol drinking water was found to promote tumor development in the mice, but only in the presence of ovarian hormones. Tumor development was associated with increased estrogen levels, increased aromatase activity (in which androgens are converted to estrogens in the body), and increased expression of ER in the tumors of the 20% alcohol ovariectomized MMTV-neu mice. Ovariectomy blocked these effects.
The authors conclude that alcohol consumption promotes HER2 breast cancer development via the estrogen signaling pathway.
Please see our articles on alcohol and on breast cancer diet for HER2+ patients and survivors for more information.