Obesity and IGF-axis Activation in Native Hawaiian Women with Breast Cancer

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DESCRIPTION (provided by applicant): Breast cancer is the most common cancer among women in the U.S. Breast cancer incidence and mortality rates vary across racial/ethnic groups, yet the majority of our biological knowledge about breast cancer is based on Caucasian women. Breast cancer is a complex disease with multiple factors such as environmental, socioeconomic, treatment, and biological factors (including genetics) influencing risk and survival. Therefore it s essential that we initiate studies including individuals from other racial/ethnic groups. Based on data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER), Native Hawaiian women have the highest breast cancer incidence and mortality rates in the nation. However detailed characterization of breast cancer biology and prognostic factors for Native Hawaiian women has been remarkably limited. Our study focuses on the established link between excess weight and breast cancer in Native Hawaiian women. Studies have shown that overweight/obese women are at greater risk of developing breast cancer and experience poorer outcomes with breast cancer. The role of excess weight for breast cancer can be particularly impactful for Native Hawaiian women because at least 70% of the Native Hawaiian women are overweight/obese. High levels of bioavailable insulin-like growth factors (IGF), as a result of insulin resistance associated with obesity, have been proposed as a candidate mechanism for the increased risk and poor survival of obese women with breast cancer. We intend to characterize the role of IGFs in Native Hawaiian breast cancer with two primary aims. In the first aim we intend to examine the role of obesity and IGF-activation in ER-positive Native Hawaiian breast cancer cases with poor and good overall and breast cancer-specific survival. IGF-pathway activation will be assessed by gene expression profiling of a panel of genes previously established to be up- or down- regulated upon IGF-1 activation. The second aim will compare the association of tissue specific expression of IGF, IGFBP, and IGFR proteins in with breast cancer-specific and overall survival for Native Hawaiian, Asian, and Caucasian women. An established annotated population-based breast cancer tissue microarray will be used to assay protein expression profiles and these profiles will be correlated with breast cancer survival. The proposed work will provide important information regarding the biological mechanisms that impact Native Hawaiian breast cancer and establish a foundation for tailored clinical strategies to target the IGF-pathway for this population.