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: 8396307
• 负责人: Nina A. Bickell
• 金额: $ 72.13万
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8396307
• 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; Epidemiologic Studies; 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; Left; 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; Patients; Pattern; Peripheral; Population; Process; Race; Randomized Controlled Trials; Receptor Signaling; Recruitment Activity; Recurrence; Reporting; Research; Risk; Role; Sampling; Screening procedure; Signal Pathway; Signal Transduction; Staging; Testing; Tissues; Woman; Work; breast cancer diagnosis; cancer therapy; cell growth; diabetic; improved; insulin signaling; malignant breast neoplasm; mortality; new therapeutic target; non-diabetic; outcome forecast; prognostic; racial difference; tumor; 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; Epidemiologic Studies; 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; Left; 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; Patients; Pattern; Peripheral; Population; Process; Race; Randomized Controlled Trials; Receptor Signaling; Recruitment Activity; Recurrence; Reporting; Research; Risk; Role; Sampling; Screening procedure; Signal Pathway; Signal Transduction; Staging; Testing; Tissues; Woman; Work; breast cancer diagnosis; cancer therapy; cell growth; diabetic; improved; insulin signaling; malignant breast neoplasm; mortality; new therapeutic target; non-diabetic; outcome forecast; prognostic; racial difference; 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. PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）：尽管乳腺癌诊断和治疗方面有所改善，但黑人乳腺癌的预后仍比白人女性差。这项研究的目的是确定胰岛素抵抗的差异是否可以解释黑人和白人妇女之间乳腺癌生存的差异。胰岛素抵抗是肥胖症，代谢综合征和早期2型糖尿病的重要组成部分，与更具侵略性的乳腺癌亚型相关的疾病以及死亡率增加。白人女性胰岛素水平较高，也与乳腺癌死亡率升高有关，尽管尚未在黑人妇女中进行研究。鉴于肥胖症和糖尿病流行不成比例地影响少数群体，因此重要的是了解高胰岛素血症的关系，肥胖，胰岛素抵抗和IR信号对乳腺癌进展的结果。了解这些关系可以解释不同种族群体中看到的疾病的不同模式，并有助于识别患者 将从有针对性的治疗中受益。我们的研究试图解决文献中的一些差距。我们有2个主要目的：目标1：检查外周胰岛素抵抗与乳腺癌与预后不良之间的关联是否有所不同。目标2：证明肿瘤的胰岛素受体和 /或IGF-1受体信号传导途径是否与较差的预后特征有关，以及该途径的激活是否在黑人和白人女性之间有所不同。我们将招募936名白人妇女和350名患有新诊断的乳腺癌的黑人妇女，以研究胰岛素抵抗，乳腺癌侵略和种族之间的联系。将收集胰岛素抵抗，代谢综合征和肥胖症的措施，以研究胰岛素是否是肥胖与乳腺癌侵略性之间关联的关键机械联系，以及种族如何影响这种关联。在对新的原发性乳腺癌的女性进行术前评估期间，将采取胰岛素抵抗和人体测量措施的血液样本。将使用免疫组织化学来检查原次手术切除过程中去除的乳腺癌组织样本，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。 公共卫生相关性：这项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妇女之间乳腺癌生存的差异。胰岛素抵抗是肥胖症，代谢综合征和早期2型糖尿病的重要组成部分，与更具侵略性的乳腺癌亚型相关的疾病以及死亡率增加。