Obesity and breast cancer: a multipartite connection.
Obesity and breast cancer: a multipartite connection.
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DOI：
10.1007/s10911-013-9306-4
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发表时间：
2013-12
影响因子：
2.5
通讯作者：
Davidson, Nancy E.
中科院分区：
文献类型：
--
作者：
Sharma, Dipali;Davidson, Nancy E.
导致肥胖和乳腺癌的肿瘤。本期包含讨论肥胖对乳腺癌影响的评论，并剖析潜在的分子网络，我们认为这些分子网络代表了介导肥胖状态对乳腺癌发生影响的关键途径。在过去的几年里，基础科学已经发展到可以开发创新工具来研究和针对肥胖与乳腺癌之间联系的关键节点的程度。将讨论这些模型和新兴的治疗靶点。这是一个非常及时的问题。过去二十年来，美国和许多其他国家的超重和肥胖患病率急剧上升。值得注意的是，肥胖是仅次于烟草的第二大癌症危险因素，近 30% 的癌症归因于肥胖。多项研究已经检验了肥胖与乳腺癌的关联。目前已知，肥胖不仅是肥胖乳腺癌患者肿瘤侵袭性增加、预后较差、复发率较高、生存期较差的危险因素，而且还会影响乳腺癌新发病例的发生。最近一项研究肥胖对乳腺癌女性生存影响的荟萃分析显示，肥胖受试者与非肥胖受试者的死亡率风险比 (HR) 为 1.30-1.35 [1]。还发现诊断时肥胖与乳腺癌复发风险增加两倍以上相关 (HR 2.43)[2]。已经进行了多项临床研究来检查在调节肥胖对乳腺癌结果的影响中发挥作用的因素。肥胖是一种复杂的生理状态，与能够调节肿瘤细胞行为以及周围微环境各方面的多种分子变化相关。对正常、超重和肥胖乳腺癌患者乳腺肿瘤的基因表达分析揭示了与肥胖相关的乳腺癌转录基因特征，当使用各种公共表达数据集进行分析时，该特征与较差的患者预后相关[3]。肥胖状态似乎调节肿瘤细胞的基因表达模式，可能改变它们的生长和转移潜力。乳腺肿瘤微环境中的多种因素可以影响乳腺肿瘤细胞。正常脂肪细胞的大小异质性通常在肥胖中消失，有利于脂肪细胞肥大（细胞大小增加）和增生（细胞数量增加）。肥大脂肪细胞数量的增加可能会产生更高水平的激素（例如雌激素），从而促进肿瘤细胞的侵袭行为[4]。此外，肿瘤微环境中分泌巨噬细胞、内皮细胞、T 细胞、肥大细胞和其他免疫细胞的浸润性 TNFα 和白细胞介素 (IL)-6 数量增加会改变肥胖条件下的肿瘤行为 [5, 6]。与肥胖相关的高胰岛素血症会促进胰岛素样生长因子-1 (IGF-1) 的生物活性，并改变促炎细胞因子、趋化因子和脂肪因子的水平和活性 [7]，导致乳腺肿瘤进展和转移。流行病学研究表明，循环胰岛素和 C 肽水平高与乳腺癌预后不良之间存在密切关系 [8, 9]。对不同人群、性别和年龄组的各种研究发现了非线性关系
Neoplasia that is devoted to obesity and breast cancer. This issue contains reviews discussing the impact of obesity on breast cancer and dissecting the underlying molecular networks that, in our opinion, represent key pathways mediating the effects of obese state on breast carcinogenesis. In the last few years, basic science has advanced to the point where innovative tools have been developed to study and target the key nodes of obesity-breast cancer link; these models and emerging therapeutic targets will be discussed. This is a very timely issue. The prevalence of overweight and obesity has dramatically increased in the last two decades in the United States and many other countries. Notably, obesity is second only to tobacco as a leading risk factor for cancer and nearly 30% of cancers are attributable to obesity. The association of obesity with breast cancer has been examined in multiple studies. It is now known that obesity is not only a risk factor for the increased tumor aggressiveness, poorer prognosis, higher rate of recurrence and poorer survival of obese breast cancer patients, but it also affects the development of new cases of breast cancer. A recent meta-analysis examining the effect of obesity on survival of women with breast cancer reported a hazard ratio (HR) of 1.30–1.35 for mortality in obese vs. non-obese subjects [1].Obesity at time of diagnosis was also found to be associated with a greater than two-fold increased risk of breast cancer recurrence (HR 2.43)[2]. Multiple clinical studies have been conducted to examine the factors that play a role in mediating the impact of obesity on breast cancer outcomes. Obesity is a complex physiologic state that is associated with multiple molecular changes capable of modulating tumor cell behavior as well as aspects of the surrounding microenvironment. Gene expression analysis of breast tumors from normal, overweight and obese breast cancer patients revealed an obesity-associated breast cancer transcriptional gene signature which correlated with worse patient outcome when analyzed using various public expression data sets [3]. Obese state appears to modulate gene expression patterns of the tumor cells, potentially altering their growth and metastatic potential. Multiple factors in the breast tumor microenvironment can influence breast tumor cells. Size heterogeneity of normal adipocytes is often lost in obesity in favor of adipocyte hypertrophy (increase in cell size) and hyperplasia (increase in cell number). Increased number of hypertrophied adipocytes may produce increased levels of hormones (eg, estrogen) to promote aggressive behavior of tumor cells [4]. Additionally, increased numbers of infiltrating TNFα and interleukin (IL)-6 secreting macrophages, endothelial cells, T-cells, mast cells and other immune cells in the tumor microenvironment alter tumor behavior in obese conditions [5, 6]. Hyperinsulinemia associated with obesity promotes the biological activity of insulin-like growth factor-1 (IGF-1) and alters the levels and activity of proinflammatory cytokines, chemokines and adipokines [7] leading to breast tumor progression and metastasis. Epidemiological studies have shown a strong relationship between high levels of circulating insulin and c-peptide and poor prognosis of breast cancer [8, 9]. Various studies of different populations, genders and age groups have found a non-linear relationship
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影响因子：
2.5
作者：
Hovey, Russell C.;Aimo, Lucila
通讯作者：
Aimo, Lucila
影响因子：
16.2
作者：
Dankner R;Shanik MH;Keinan-Boker L;Cohen C;Chetrit A
通讯作者：
Chetrit A
影响因子：
2.3
作者：
Kamineni，Aruna;Anderson，Melissa L.;Buist，Diana S. M.
通讯作者：
Buist，Diana S. M.
影响因子：
4.7
作者：
Pacher, Margit;Seewald, Michael J.;Schreiber, Martin
通讯作者：
Schreiber, Martin
影响因子：
45.3
作者：
Goodwin, PJ;Ennis, M;Hood, N
通讯作者：
Hood, N