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有所改善，但患有乳腺癌的黑人妇女的预后仍然比白色妇女差。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色妇女之间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型糖尿病的重要组成部分，与更侵袭性的乳腺癌亚型和死亡率增加相关。白色妇女的胰岛素水平较高也与乳腺癌死亡率增加有关，尽管这还没有在黑人妇女中进行过研究。鉴于肥胖和糖尿病流行不成比例地影响少数群体，重要的是要了解高胰岛素血症，肥胖，胰岛素抵抗和增加的IR信号传导对乳腺癌进展的结果的关系。了解这些关系可以解释不同种族群体中不同的疾病模式，并有助于识别 会从靶向治疗中获益我们的研究试图解决文献中的一些空白。我们有两个主要目标：目标1：研究外周胰岛素抵抗与乳腺癌预后不良之间的关系在黑人和白色妇女中是否存在差异。目标二：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色女性之间是否存在差异。我们将招募936名白色女性和350名新诊断乳腺癌的黑人女性，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措施，以调查胰岛素是否是肥胖和乳腺癌侵袭性之间的关联的关键机制环节，以及种族如何影响这种关联。在对新发原发性乳腺癌妇女进行术前评估期间，将采集胰岛素抵抗和人体测量的血样。将使用免疫组织化学检查在初次手术切除期间取出的乳腺癌组织样本，以评估胰岛素、胰岛素样差异在种族组之间乳腺癌预后中的作用。