Insulin Resistance and Breast Cancer Prognosis in Black & White Women

描述(申请人提供)：尽管乳腺癌的诊断和治疗有所改善，但患有乳腺癌的黑人女性的预后仍然比白人女性差。这项研究的目的是确定胰岛素抵抗的差异是否可以部分解释黑人和白人女性乳腺癌存活率的差异。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，这些疾病与更具侵袭性的乳腺癌亚型和增加的死亡率相关。白人女性较高的胰岛素水平也与乳腺癌死亡率的增加有关，尽管这一点尚未在黑人女性中进行研究。鉴于肥胖和糖尿病的流行对少数群体的影响不成比例，了解由肥胖、胰岛素抵抗和IR信号增加导致的高胰岛素血症与乳腺癌进展的关系是重要的。了解这些关系可以解释不同种族群体中出现的不同疾病模式，并有助于识别 会从靶向治疗中受益。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系是否存在差异。目的：探讨肿瘤的胰岛素受体和/或胰岛素样生长因子-1受体信号通路是否与预后不良有关，以及该通路的激活在黑人和白人女性中是否存在差异。我们将招募936名患有新诊断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指标，以调查胰岛素是否是肥胖和乳腺癌侵袭性之间关联的关键机制链接，以及种族如何影响这种关联。在对患有新的原发乳腺癌的妇女进行术前评估期间，将采集血液样本进行胰岛素抵抗和人体测量。在初次手术切除过程中切除的乳腺癌组织样本将通过免疫组织化学进行检查，以评估不同种族之间胰岛素的作用，胰岛素样差异在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女性乳腺癌存活率的差异。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，这些疾病与更具侵袭性的乳腺癌亚型和增加的死亡率相关。

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.