Gallagher Emily J, LeRoith Derek, Franco Rebeca, Antoniou Irini Markella, Nayak Anupma, Livaudais-Toman Jennifer, Bickell Nina A
Icahn School of Medicine at Mount Sinai, Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, New York, NY, USA.
Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy, Department of Medicine, New York, NY, USA.
Diabetes Metab Res Rev. 2016 Oct;32(7):745-753. doi: 10.1002/dmrr.2795. Epub 2016 Apr 21.
Women with obesity and type 2 diabetes (T2D) are at greater risk of dying from breast cancer than women without these conditions. Obesity and T2D are associated with insulin resistance and endogenous hyperinsulinemia and are more common in Black women. There is increasing disparity in breast cancer mortality between Black and White women in the USA. We hypothesize that insulin resistance and endogenous hyperinsulinemia in Black women with breast cancer contribute to their greater breast cancer mortality and are associated with increased insulin receptor signalling in tumours.
We will recruit 350 Black women and 936 White women with newly diagnosed breast cancer. We will determine the presence or absence of the metabolic syndrome/pre-diabetes and insulin resistance by measuring body mass index, waist circumference, lipids, blood pressure, glucose, insulin-like growth factor binding protein 1 and insulin. Breast cancer prognosis will be determined by a Nottingham Prognostic Index (NPI), with poor prognosis being defined as NPI >4.4. Tumour insulin receptor signalling will be determined by immunohistochemistry. Insulin receptor subtype expression will be measured using Nanostring. Analysis of these factors will determine whether endogenous hyperinsulinemia is associated with a worse prognosis in Black women than White women and increased tumour insulin receptor signalling.
The results of this study will determine if the metabolic syndrome and pre-diabetes contribute to racial disparities in breast cancer mortality. It may provide the basis for targeting systemic insulin resistance and/or tumour insulin receptor signalling to reduce racial disparities in breast cancer mortality. Copyright © 2016 John Wiley & Sons, Ltd.
患有肥胖症和2型糖尿病（T2D）的女性死于乳腺癌的风险高于未患这些疾病的女性。肥胖症和T2D与胰岛素抵抗和内源性高胰岛素血症相关，且在黑人女性中更为常见。在美国，黑人女性和白人女性之间的乳腺癌死亡率差距日益增大。我们推测，患有乳腺癌的黑人女性的胰岛素抵抗和内源性高胰岛素血症导致了她们更高的乳腺癌死亡率，并且与肿瘤中胰岛素受体信号传导增加有关。
我们将招募350名新诊断为乳腺癌的黑人女性和936名白人女性。我们将通过测量体重指数、腰围、血脂、血压、血糖、胰岛素样生长因子结合蛋白1和胰岛素来确定是否存在代谢综合征/糖尿病前期和胰岛素抵抗。乳腺癌预后将通过诺丁汉预后指数（NPI）来确定，预后不良定义为NPI>4.4。肿瘤胰岛素受体信号传导将通过免疫组织化学来确定。胰岛素受体亚型表达将使用Nanostring进行测量。对这些因素的分析将确定内源性高胰岛素血症是否与黑人女性比白人女性更差的预后以及肿瘤胰岛素受体信号传导增加有关。
本研究结果将确定代谢综合征和糖尿病前期是否导致乳腺癌死亡率的种族差异。它可能为针对全身性胰岛素抵抗和/或肿瘤胰岛素受体信号传导以减少乳腺癌死亡率的种族差异提供依据。版权所有© 2016约翰·威利父子有限公司。
