Cheng Ting-Yuan David, Omilian Angela R, Yao Song, Sanchez Pamela V, Polk Latasia Z, Zhang Weizhou, Datta Susmita, Bshara Wiam, Ondracek Rochelle Payne, Davis Warren, Liu Song, Hong Chi-Chen, Bandera Elisa V, Khoury Thaer, Ambrosone Christine B
Department of Epidemiology, University of Florida, Gainesville, FL USA.
Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY USA.
NPJ Breast Cancer. 2020 Sep 21;6:45. doi: 10.1038/s41523-020-00187-4. eCollection 2020.
Energy imbalance has an important role in breast cancer prognosis. Hyperactive mechanistic Target of Rapamycin (mTOR) pathway is associated with breast tumor growth, but the extent to which body fatness is associated with mTOR pathway activities in breast cancer is unclear. We performed immunostaining for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-p70S6K in tumor tissue from 590 women (464 African Americans/Blacks and 126 Whites) with newly diagnosed invasive breast cancer in the Women's Circle of Health Study. Anthropometric measures were taken by study staff, and body composition was measured by bioelectrical impedance analysis. Linear regressions were used to estimate percent differences in protein expression between categories of body mass index (BMI), waist circumference, waist/hip ratio, fat mass, fat mass index, and percent body fat. We observed that BMI ≥ 35.0 vs. <25 kg/m was associated with 108.3% (95% CI = 16.9%-270.9%) and 101.8% (95% CI = 17.0%-248.8%) higher expression in p-mTOR and normalized p-mTOR, i.e., p-mTOR/mTOR, respectively. Quartiles 4 vs. 1 of waist/hip ratio was associated with 41.8% (95% CI = 5.81%-89.9%) higher mTOR expression. Similar associations were observed for the body fat measurements, particularly in patients with estrogen receptor-negative (ER-) tumors, but not in those with ER+ tumors, although the differences in associations were not significant. This tumor-based study found positive associations between body fatness and mTOR pathway activation, evident by a p-mTOR expression, in breast cancer. Our findings suggest that mTOR inhibition can be a treatment strategy to prevent the recurrence of these tumors in obese individuals.
能量失衡在乳腺癌预后中起着重要作用。雷帕霉素机制性靶标（mTOR）通路过度活跃与乳腺肿瘤生长相关，但身体肥胖与乳腺癌中mTOR通路活性的关联程度尚不清楚。在“健康女性圈研究”中，我们对590名新诊断为浸润性乳腺癌的女性（464名非裔美国人/黑人及126名白人）的肿瘤组织进行了mTOR、磷酸化（p）-mTOR、p-AKT和p-p70S6K的免疫染色。研究人员进行了人体测量，并通过生物电阻抗分析测量了身体成分。采用线性回归来估计体重指数（BMI）、腰围、腰臀比、脂肪量、脂肪量指数和体脂百分比类别之间蛋白质表达的百分比差异。我们观察到，BMI≥35.0与<25kg/m²相比，p-mTOR和标准化p-mTOR（即p-mTOR/mTOR）的表达分别高108.3%（95%CI=16.9%-270.9%）和101.8%（95%CI=17.0%-248.8%）。腰臀比的第4四分位数与第1四分位数相比，mTOR表达高41.8%（95%CI=5.81%-89.9%）。在身体脂肪测量中也观察到了类似的关联，尤其是在雌激素受体阴性（ER-）肿瘤患者中，但在ER+肿瘤患者中未观察到，尽管关联差异不显著。这项基于肿瘤的研究发现，身体肥胖与乳腺癌中mTOR通路激活之间存在正相关，这在p-mTOR表达中很明显。我们的研究结果表明，抑制mTOR可能是预防肥胖个体这些肿瘤复发的一种治疗策略。
