虽然生活压力在乳腺癌发病中的作用尚不清楚，但社交孤立与乳腺癌风险和死亡率的增加是一致的。社交孤立可以定义为孤独或缺乏感知到的社交联系。在雌性小鼠和大鼠中，社交孤立通过将动物单独地放置在笼子里来模拟。社交孤立引起许多生物学变化，其中包括炎症标志物的增加和线粒体和细胞代谢的紊乱。目前尚不清楚两种传统应激途径，即下丘脑-垂体-肾上腺轴（HPA）导致肾上腺皮质释放糖皮质激素和自主神经系统（ANS）导致肾上腺髓质和后神经节神经元释放儿茶酚胺的方式如何解释社交孤立个体乳腺癌风险的增加。例如，糖皮质激素受体在雌激素受体阳性的乳腺癌细胞中的激活抑制了细胞的增殖，并且β肾上腺素能受体（β-AR）的激活在不成熟的免疫细胞中促进了它们向抗肿瘤的T细胞的分化。然而，HPA和ANS通路的激活可能导致大脑-肠道-菌群轴的紊乱，从而导致肠道微生物失调。肠道微生物失调反过来会导致细菌代谢物（如短链脂肪酸）的产生改变，引发全身轻度慢性炎症，诱导线粒体和细胞代谢功能失调。社交孤立诱导的乳腺癌风险和死亡率增加与肠道微生物失调之间可能存在着因果关系，应予以调查，因为这提供了预防乳腺癌的新工具。 © 作者 2023 年。由牛津大学出版社代表内分泌学会出版。保留所有权利。有关权限，请发送电子邮件至：journals.permissions@oup.com。

Although the role of life-stressors in breast cancer remains unclear, social isolation is consistently associated with increased breast cancer risk and mortality. Social isolation can be defined as loneliness or an absence of perceived social connections. In female mice and rats, social isolation is mimicked by housing animals one per cage. Social isolation causes many biological changes, of which an increase in inflammatory markers and disruptions in mitochondrial and cellular metabolism are commonly reported. It is not clear how the two traditional stress-induced pathways, i.e., hypothalamic-pituitary axis (HPA), resulting a release of glucocorticoids from the adrenal cortex, and autonomic nervous system (ANS), resulting a release of catecholamines from the adrenal medulla and post-ganglionic neurons, could explain the increased breast cancer risk in socially isolated individuals. For example, glucocorticoid receptor activation in estrogen receptor positive breast cancer cells inhibits their proliferation, and activation of β-adrenergic receptor (β-AR) in immature immune cells promotes their differentiation towards anti-tumorigenic T cells. However, activation of HPA and ANS pathways may cause a disruption in the brain-gut-microbiome axis, resulting gut dysbiosis. Gut dysbiosis, in turn, leads to an alteration in the production of bacterial metabolites, such as short chain fatty acids, causing a systemic low-grade inflammation and inducing dysfunction in mitochondrial and cellular metabolism. A possible causal link between social isolation -induced increased breast cancer risk and mortality and gut dysbiosis should be investigated, as it offers new tools to prevent breast cancer.© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.