Impact Of Obesity On Tamoxifen Chemoprevention In A Model Of Ductal Carcinoma In Situ
Abstract
Obesity increases risk for breast cancer in postmenopausal women and increases mortality in pre- and postmenopausal women, in fact, 30-50% of breast cancer deaths in post-menopausal women may be attributed to excess body weight (1). The HER-2/neu proto-oncogene is amplified in 25-30% of human primary breast cancers, and increased levels of HER-2/neu expression in tumors can have a negative impact on prognosis of the cancer (2). Approximately two-thirds of breast cancers arising in postmenopausal women are positive for estrogen receptor (ER) in carcinoma cells. However, tumors negative for estrogen receptor (ER-) confer a much worse prognosis (3). Energy balance modulation through diet-induced obesity and calorie restriction has been shown to modulate serum levels of many growth factors and hormones, including estrogen. Additionally, energy balance modulation affects cancer initiation and progression multiple mouse and primate models (4). However, the specific mechanisms by which obesity affects ER- breast cancer risk or prognosis are not clearly understood, and strategies for offsetting the negative effects of obesity are urgently needed, so the purpose of my project is twofold. First, we will determine which obesity-related growth factors/hormones are key to tumor progression. Second, we will determine how blocking specific growth factors (specifically components of the IGF-I pathway) can decrease the negative effects of obesity on breast cancer and increase response to chemopreventive drugs (chemopreventive drugs are compounds given to prevent breast cancer, i.e. tamoxifen). This annual report summarizes the characterization of the effects of dietary energy balance modulation on metabolic hormones and mammary tumor development, growth, and progression in MMTV-neu (HER-2/neu overexpressing) mice (Specific Aim 1).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA555053
Entities
People
- Sarah D. Smith
Organizations
- University of Texas at Austin