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

描述（由申请人提供）：乳腺癌是美国女性中最常见的癌症。乳腺癌的发病率和死亡率因种族/民族而异，但我们对乳腺癌的大部分生物学知识都是基于白种人妇女。乳腺癌是一种复杂的疾病，有多种因素，如环境、社会经济、治疗和生物因素（包括遗传）影响风险和生存。因此，我们有必要开展包括其他种族/民族群体的研究。根据国家癌症研究所的监测流行病学和最终结果（SEER）的数据，夏威夷土著妇女的乳腺癌发病率和死亡率在全国最高。然而，对夏威夷土著妇女乳腺癌生物学和预后因素的详细描述非常有限。我们的研究重点是在夏威夷土著妇女中超重和乳腺癌之间建立的联系。研究表明，超重/肥胖的女性患乳腺癌的风险更大，乳腺癌的预后也更差。超重对乳腺癌的影响对夏威夷土著妇女尤其严重因为至少70%的夏威夷土著妇女超重/肥胖。高水平的生物可利用胰岛素样生长因子（IGF），作为与肥胖相关的胰岛素抵抗的结果，被认为是肥胖女性乳腺癌风险增加和生存不良的候选机制。我们打算描述igf在夏威夷原住民乳腺癌中的作用，主要有两个目的。在第一个目标中，我们打算研究肥胖和igf激活在er阳性的夏威夷原住民乳腺癌病例中的作用，这些病例的总体生存率和乳腺癌特异性生存率分别较差和较好。igf通路的激活将通过一组基因的基因表达谱来评估，这些基因先前被确定为在IGF-1激活时上调或下调。第二个目的是比较IGF、IGFBP和IGFR蛋白的组织特异性表达与夏威夷土著、亚洲和高加索妇女乳腺癌特异性和总体生存率的关系。已建立的基于人群的注释乳腺癌组织微阵列将用于测定蛋白质表达谱，这些谱将与乳腺癌生存率相关。这项工作将为影响夏威夷原住民乳腺癌的生物学机制提供重要信息，并为针对这一人群的igf通路制定量身定制的临床策略奠定基础。

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.