The mechanistic target of rapamycin (mTOR) pathway promoted by positive energy imbalance and insulin-like growth factors can be a mechanism by which obesity influences breast cancer risk. We evaluated the associations of body fatness with the risk of breast cancer varied with phosphorylated (p)-mTOR protein expression, an indication of the pathway activation. Women with newly diagnosed breast cancer (n = 715; 574 [80%] Black and 141 [20%] White) and non-cancer controls (n = 1983; 1280 [64%] Black and 713 [36%] White) were selected from the Women’s Circle of Health Study. Surgical tumor samples among the cases were immunostained for p-mTOR (Ser2448) and classified as p-mTOR-overexpressed, if the expression level ≥ 75th percentile, or p-mTOR-negative/low otherwise. Anthropometrics were measured by trained staff, and body composition was determined by bioelectrical impedance analysis. Odds ratios (ORs) of p-mTOR-overexpressed tumors and p-mTOR-negative/low tumors compared to controls were estimated using polytomous logistic regression. The differences in the associations by the p-mTOR expression status were assessed by tests for heterogeneity. Cases with p-mTOR-overexpressed tumors, but not cases with p-mTOR-negative/low tumors, compared to controls were more likely to have higher body mass index (BMI), percent body fat, and fat mass index (P-heterogeneity < 0.05), although the OR estimates were not significant. For the measurement of central adiposity, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 2.52, 95% CI = 1.46 to 4.34) and Q4 (OR = 1.99, 95% CI = 1.12 to 3.50) of waist circumference (WC) compared to controls. Similarly, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 1.82, 95% CI = 1.11 to 2.98) and Q4 (OR = 1.81, 95% CI = 1.11 to 2.98) of WHR compared to controls. These associations of WC and waist-to-hip ratio (WHR) did not differ by tumor p-mTOR status (P-heterogeneity = 0.27 and 0.48, respectively). Our findings suggest that in this population composed of predominately Black women, body fatness is associated with breast cancer differently for p-mTOR overexpression and p-mTOR negative/low expression. Whether mTOR plays a role in the obesity and breast cancer association warrants confirmation by prospective studies.

中文翻译：

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在以黑人女性为主的样本中，体脂和乳腺癌风险与磷酸化 mTOR 表达相关

正能量失衡和胰岛素样生长因子促进的雷帕霉素 (mTOR) 通路的机制靶点可能是肥胖影响乳腺癌风险的机制。我们评估了身体肥胖与乳腺癌风险的关联，随磷酸化 (p)-mTOR 蛋白表达而变化，这是通路激活的一个迹象。新诊断的乳腺癌妇女（n = 715；574 [80%] 黑人和 141 [20%] 白人）和非癌症对照妇女（n = 1983；1280 [64%] 黑人和 713 [36%] 白人）是选自女性健康研究圈。病例中的手术肿瘤样本对 p-mTOR (Ser2448) 进行免疫染色，如果表达水平≥ 75%，则归类为 p-mTOR 过表达，否则归类为 p-mTOR 阴性/低。人体测量学由训练有素的工作人员测量，并且通过生物电阻抗分析确定身体成分。使用多分逻辑回归估计 p-mTOR 过表达肿瘤和 p-mTOR 阴性/低肿瘤与对照相比的优势比 (OR)。通过异质性测试评估 p-mTOR 表达状态的关联差异。与对照组相比，具有 p-mTOR 过表达肿瘤的病例，但不是具有 p-mTOR 阴性/低肿瘤的病例，更有可能具有更高的体重指数 (BMI)、体脂百分比和脂肪质量指数（P-异质性） < 0.05)，尽管 OR 估计值不显着。对于中心性肥胖的测量，p-mTOR 过表达肿瘤的病例在 Q3（OR = 2.52，95% CI = 1.46 至 4.34）和 Q4（OR = 1.99，95% CI = 1.12 至 3.50）的几率更高) 的腰围 (WC) 与对照相比。类似地，与 WHR 相比，p-mTOR 过表达肿瘤病例在第三季度（OR = 1.82，95% CI = 1.11 至 2.98）和第四季度（OR = 1.81，95% CI = 1.11 至 2.98）的几率更高控件。WC 和腰臀比 (WHR) 的这些关联不因肿瘤 p-mTOR 状态而异（P-异质性分别 = 0.27 和 0.48）。我们的研究结果表明，在这个主要由黑人女性组成的人群中，身体肥胖与乳腺癌的相关性不同，p-mTOR 过表达和 p-mTOR 阴性/低表达。mTOR 是否在肥胖和乳腺癌关联中起作用需要前瞻性研究证实。WC 和腰臀比 (WHR) 的这些关联不因肿瘤 p-mTOR 状态而异（P-异质性分别 = 0.27 和 0.48）。我们的研究结果表明，在这个主要由黑人女性组成的人群中，身体肥胖与乳腺癌的相关性不同，p-mTOR 过表达和 p-mTOR 阴性/低表达。mTOR 是否在肥胖和乳腺癌关联中起作用需要前瞻性研究证实。WC 和腰臀比 (WHR) 的这些关联不因肿瘤 p-mTOR 状态而异（P-异质性分别 = 0.27 和 0.48）。我们的研究结果表明，在这个主要由黑人女性组成的人群中，身体肥胖与乳腺癌的相关性不同，p-mTOR 过表达和 p-mTOR 阴性/低表达。mTOR 是否在肥胖和乳腺癌关联中起作用需要前瞻性研究证实。