Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, 1428 Madison Avenue, Box 1055, New York, NY, 10029, USA.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Breast Cancer Res. 2020 May 12;22(1):40. doi: 10.1186/s13058-020-01281-y.
Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women.
We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) > 4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC).
Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p < 0.0001). HOMA-IR was higher in Black women than in White women (1.9 ± 1.2 vs 1.3 ± 1.4, p = 0.0005). Poor breast cancer prognosis was more prevalent in Black women than in White women (28% vs 15%. p = 0.004). HOMA-IR was positively associated with NPI score (r = 0.1, p = 0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (β = 0.04, 95% CI 0.005-0.009, p = 0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p = 0.004), and greater IR/IGF-1R ratio was also associated with higher NPI score (IR/IGF-1R > 1: 4.2 ± 0.8 vs IR/IGF-1R = 1: 3.9 ± 0.8 vs IR/IGF-1R < 1: 3.5 ± 1.0, p < 0.0001).
In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.
黑人和白人女性在所有乳腺癌阶段的乳腺癌生存方面都存在种族差异。胰岛素抵抗的代谢综合征（MetS）不成比例地影响更多的黑人女性比白人女性。尚未确定胰岛素抵抗是否介导了种族与乳腺癌预后不良之间的联系。我们旨在确定胰岛素抵抗是否部分介导了种族与乳腺癌预后之间的关联，以及黑人女性和白人女性的肿瘤中胰岛素受体（IR）和胰岛素样生长因子受体（IGF-1R）的表达是否存在差异。
我们进行了一项跨十个医院的横断面、多中心研究。招募了新诊断为浸润性乳腺癌的自我认定的黑人女性和白人女性。主要结局是使用多元线性中介模型确定胰岛素抵抗（使用稳态模型评估的胰岛素抵抗（HOMA-IR））是否部分介导了种族对预后的影响。收集人口统计学数据、人体测量测量和空腹血液。预后不良定义为诺丁汉预后指数（NPI）>4.4。通过免疫组织化学（IHC）评估乳腺癌病理标本中 IR 和 IGF-1R 的表达。
共招募了 515 名女性（83%为白人，17%为黑人）。黑人女性的代谢综合征比白人女性更普遍（40%比 20%，p<0.0001）。黑人女性的 HOMA-IR 高于白人女性（1.9±1.2 比 1.3±1.4，p=0.0005）。黑人女性的不良乳腺癌预后比白人女性更普遍（28%比 15%，p=0.004）。HOMA-IR 与 NPI 评分呈正相关（r=0.1，p=0.02）。调整年龄后的中介模型表明，HOMA-IR 显著介导了黑人种族与不良预后之间的关联（β=0.04，95%CI 0.005-0.009，p=0.002）。黑人女性肿瘤中的 IR 表达高于白人女性（79%比 52%，p=0.004），并且更高的 IR/IGF-1R 比值也与更高的 NPI 评分相关（IR/IGF-1R>1:4.2±0.8 比 IR/IGF-1R=1:3.9±0.8 比 IR/IGF-1R<1:3.5±1.0，p<0.0001）。
在这项针对新诊断为浸润性乳腺癌的美国女性的多中心、横断面研究中，胰岛素抵抗是介导种族与乳腺癌预后不良之间部分关联的因素之一。
