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Impact Of Obesity On Tamoxifen Chemoprevention In A Model Of Ductal Carcinoma In Situ

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Annual summary 15 Sep 2010-14 Sep 2011

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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-2neu proto-oncogene is amplified in 25-30 of human primary breast cancers, and increased levels of HER-2neu 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 factorshormones 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-2neu overexpressing mice Specific Aim 1.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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