Excess body fat and sedentary behavior are associated with increased breast cancer risk and mortality, including in normal weight women. To investigate underlying mechanisms, we examined whether adiposity and exercise impact the breast microenvironment (e.g., inflammation and aromatase expression) and circulating metabo-inflammatory factors. In a cross-sectional cohort study, breast white adipose tissue (WAT) and blood were collected from 100 women undergoing mastectomy for breast cancer risk reduction or treatment. Self-reported exercise behavior, body composition measured by dual-energy x-ray absorptiometry (DXA), and waist:hip ratio were obtained prior to surgery. Breast WAT inflammation (B-WATi) was assessed by IHC and aromatase expression was assessed by quantitative PCR. Metabolic and inflammatory blood biomarkers that are predictive of breast cancer risk and progression were measured. B-WATi was present in 56 of 100 patients and was associated with older age, elevated BMI, postmenopausal status, decreased exercise, hypertension and dyslipidemia ( P s < 0.001). Total body fat and trunk fat correlated with B-WATi and breast aromatase levels ( P s < 0.001). Circulating C-reactive protein, IL6, insulin, and leptin positively correlated with body fat and breast aromatase levels, while negative correlations were observed for adiponectin and sex hormone binding globulin ( P < 0.001). Inverse relationships were observed with exercise ( P s < 0.05). In a subgroup of 39 women with normal BMI, body fat levels positively correlated with B-WATi and aromatase expression ( P s < 0.05). In conclusion, elevated body fat levels and decreased exercise are associated with protumorigenic micro- and host environments in normal, overweight, and obese individuals. These findings support the development of BMI-agnostic lifestyle interventions that target adiposity. Prevention Relevance: We report that individuals with high body fat and low exercise levels have breast inflammation, higher breast aromatase expression, and levels of circulating metabo-inflammatory factors that have been associated with increased breast cancer risk. These findings support interventions to lower adiposity, even among normal weight individuals, to prevent tumor growth.

中文翻译：

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肥胖和运动对高危或诊断为乳腺癌的女性乳腺组织和全身代谢炎症因子的影响

体内脂肪过多和久坐行为与乳腺癌风险和死亡率增加有关，包括在正常体重女性中。为了研究潜在的机制，我们检查了肥胖和运动是否影响乳房微环境（例如炎症和芳香酶表达）和循环代谢炎症因子。在一项横断面队列研究中，收集了 100 名接受乳房切除术以降低或治疗乳腺癌风险的女性的乳房白色脂肪组织 (WAT) 和血液。在手术前获得自我报告的运动行为、双能 X 射线吸收仪 (DXA) 测量的身体成分和腰臀比。通过 IHC 评估乳房 WAT 炎症 (B-WATi)，并通过定量 PCR 评估芳香酶表达。测量了预测乳腺癌风险和进展的代谢和炎症血液生物标志物。B-WATi 出现在 100 名患者中的 56 名中，与年龄较大、BMI 升高、绝经后状态、运动减少、高血压和血脂异常有关（P s < 0.001）。全身脂肪和躯干脂肪与 B-WATi 和乳房芳香化酶水平相关 ( P s < 0.001)。循环C反应蛋白、IL6、胰岛素和瘦素与体脂和乳房芳香化酶水平呈正相关，而脂联素和性激素结合球蛋白呈负相关（P < 0.001）。运动与运动呈负相关（P s < 0.05）。在 39 名 BMI 正常的女性亚组中，体脂水平与 B-WATi 和芳香酶表达呈正相关（ P s < 0.05）。综上所述，体脂水平升高和运动减少与正常、超重和肥胖个体的促肿瘤微生物和宿主环境有关。这些发现支持开发针对肥胖的与 BMI 无关的生活方式干预措施。预防相关性：我们报告高体脂和低运动水平的个体有乳房炎症、更高的乳房芳香酶表达和与乳腺癌风险增加相关的循环代谢炎症因子水平。这些发现支持降低肥胖的干预措施，即使是在正常体重的个体中，也可以防止肿瘤生长。这些发现支持开发针对肥胖的与 BMI 无关的生活方式干预措施。预防相关性：我们报告高体脂和低运动水平的个体有乳房炎症、更高的乳房芳香酶表达和与乳腺癌风险增加相关的循环代谢炎症因子水平。这些发现支持降低肥胖的干预措施，即使是在正常体重的个体中，也可以防止肿瘤生长。这些发现支持开发针对肥胖的与 BMI 无关的生活方式干预措施。预防相关性：我们报告高体脂和低运动水平的个体有乳房炎症、更高的乳房芳香酶表达和与乳腺癌风险增加相关的循环代谢炎症因子水平。这些发现支持降低肥胖的干预措施，即使是在正常体重的个体中，也可以防止肿瘤生长。