Insulin Resistance and Breast Cancer Prognosis in Black & White Women

黑人的胰岛素抵抗和乳腺癌预后

• 批准号: 9294967
• 负责人: Nina A. Bickell
• 金额: $ 52.51万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-09 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9294967
• 关键词: Address; Adjuvant; Affect; African American; Aggressive behavior; Animal Model; Blood specimen; Breast Cancer Risk Factor; Cancer Patient; Cancer Prognosis; Cell Proliferation; Cessation of life; Diabetes Mellitus; Disease; Distant; Epidemic; Evaluation; Excision; Exhibits; Goals; Growth; Growth Factor; Hormone Receptor; Hyperinsulinism; Immunohistochemistry; Incidence; Insulin; Insulin Receptor; Insulin Resistance; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Receptor; Insulin-Like-Growth Factor I Receptor; Link; Literature; Mammary Neoplasms; Measures; Mediating; Metabolic syndrome; Metformin; Minority; Mus; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Outcome; Pathway interactions; Patient Recruitments; Patients; Pattern; Peripheral; Population; Process; Race; Randomized Controlled Trials; Receptor Signaling; Recruitment Activity; Recurrence; Reporting; Research; Risk; Role; Sampling; Signal Pathway; Signal Transduction; Testing; Tissues; Woman; Work; breast cancer diagnosis; breast cancer survival; cancer subtypes; cancer therapy; cell growth; diabetic; epidemiology study; improved; insulin signaling; malignant breast neoplasm; mortality; new therapeutic target; non-diabetic; outcome forecast; prognostic; racial difference; racial disparity; screening; targeted cancer therapy; targeted treatment; tumor

DESCRIPTION (provided by applicant): Despite improvements in breast cancer diagnosis and treatment, Black women with breast cancer continue to have a worse prognosis than White women. The purpose of this study is to determine whether differences in insulin resistance can explain in part the disparities in breast cancer survival between Black and White women. Insulin resistance is an important component of obesity, the metabolic syndrome and early stage type 2 diabetes, conditions associated with more aggressive breast cancer subtypes and increased mortality. Higher insulin levels in White women have also been associated with increased breast cancer mortality, although this has not been studied in Black women. Given that obesity and diabetes epidemics disproportionately affect minority populations, it is important understand the relationship of hyperinsulinemia, a result of obesity, insulin resistance and increased IR signaling on the progression of breast cancer. Understanding these relationships could explain the different patterns of disease seen in different racial groups and help to identify patients who would benefit from targeted therapy. Our research attempts to address some of these gaps in the literature. We have 2 main aims: Aim 1: To examine whether the association between peripheral insulin resistance and breast cancer with a poor prognosis differs between black and white women. Aim 2: To demonstrate whether the tumor's insulin receptor and / or IGF-1 receptor signaling pathway is associated with poor prognostic features and whether activation of this pathway differs between black and white women. We will recruit 936 white women and 350 black women with a newly diagnosed breast cancer, to investigate the links between insulin resistance, breast cancer aggression, and race. Measures of insulin resistance, the metabolic syndrome and obesity will be collected to investigate whether insulin is a key mechanistic link in the association between obesity and breast cancer aggressivity, and how race affects this association. Blood samples for insulin resistance and anthropometric measures will be taken during the pre-operative evaluation of women with a new primary breast cancer. Samples of breast cancer tissue removed during primary surgical resection will be examined using immunohistochemistry to assess the role of insulin, insulin-like disparities in breast cancer prognosis between racial groups.

描述（由申请人提供）：尽管乳腺癌诊断和治疗取得了进步，但患有乳腺癌的黑人女性的预后仍然比白人女性更差。本研究的目的是确定胰岛素抵抗的差异是否可以部分解释黑人和白人女性乳腺癌生存率的差异。胰岛素抵抗是肥胖、代谢综合征和早期 2 型糖尿病、与更具侵袭性的乳腺癌亚型和死亡率增加相关的疾病的重要组成部分。白人女性较高的胰岛素水平也与乳腺癌死亡率增加有关，尽管尚未在黑人女性中进行研究。鉴于肥胖和糖尿病流行对少数群体的影响尤为严重，了解高胰岛素血症（肥胖、胰岛素抵抗和 IR 信号增强导致的乳腺癌进展）之间的关系非常重要。了解这些关系可以解释不同种族群体中所见的不同疾病模式，并有助于识别患有哪些疾病的患者 将受益于靶向治疗。我们的研究试图解决文献中的一些空白。我们有 2 个主要目标： 目标 1：研究黑人和白人女性外周胰岛素抵抗与预后不良的乳腺癌之间的关联是否存在差异。目标 2：证明肿瘤的胰岛素受体和/或 IGF-1 受体信号通路是否与不良预后特征相关，以及该通路的激活在黑人和白人女性之间是否存在差异。我们将招募 936 名新诊断出乳腺癌的白人女性和 350 名黑人女性，以调查胰岛素抵抗、乳腺癌侵袭性和种族之间的联系。将收集胰岛素抵抗、代谢综合征和肥胖的测量结果，以研究胰岛素是否是肥胖和乳腺癌侵袭性之间关联的关键机制联系，以及种族如何影响这种关联。在对患有新原发性乳腺癌的女性进行术前评估期间，将采集胰岛素抵抗的血样和人体测量指标。将使用免疫组织化学检查初次手术切除期间取出的乳腺癌组织样本，以评估胰岛素的作用以及胰岛素样差异在种族群体之间乳腺癌预后中的差异。