Ligibel Jennifer A, Strickler Howard D
From the Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA; the Department of Epidemiology & Population Health, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY.
Am Soc Clin Oncol Educ Book. 2013:52-9. doi: 10.14694/EdBook_AM.2013.33.52.
A positive association between obesity and the risk of incident postmenopausal breast cancer has been consistently observed in epidemiologic studies. Although most studies of premenopausal women have not found a similar relationship between breast cancer and obesity, the prognosis for both pre- and postmenopausal breast cancer is substantially worse among obese than normal-weight individuals. Increasing evidence suggests that these associations may be mechanistically related to sex hormones, insulin, and certain adipokines. Insulin, for example, has important mitogenic/antiapoptotic activity in addition to its metabolic effects, and many breast tumors express high levels of the insulin receptor (IR)-A isoform. Further, the use of metformin, a diabetes medication that reduces insulin levels, has been epidemiologically associated with reduced breast cancer risk among patients with diabetes, and a recent observational study found a higher rate of pathologic complete responses among patients with diabetes and breast cancer who were using metformin. Formal clinical trials of metformin as adjuvant breast cancer therapy have been initiated and are ongoing. Similarly, the effect of lifestyle changes on breast cancer outcomes is actively being investigated. Several lifestyle intervention studies have demonstrated that weight loss, increased physical activity, and dietary changes are feasible in breast cancer populations, and that individuals who make lifestyle changes after breast cancer diagnosis experience several physical and psychologic benefits. In this article, the authors review the evidence linking obesity with breast cancer risk and outcomes and provide an overview of lifestyle intervention studies in patients with breast cancer.
流行病学研究一致观察到肥胖与绝经后乳腺癌发病风险之间存在正相关。尽管大多数针对绝经前女性的研究未发现乳腺癌与肥胖之间存在类似关系，但肥胖的绝经前和绝经后乳腺癌患者的预后均明显差于体重正常者。越来越多的证据表明，这些关联可能在机制上与性激素、胰岛素和某些脂肪因子有关。例如，胰岛素除了具有代谢作用外，还具有重要的促有丝分裂/抗凋亡活性，许多乳腺肿瘤表达高水平的胰岛素受体（IR）-A亚型。此外，使用二甲双胍这种降低胰岛素水平的糖尿病药物，在流行病学上与糖尿病患者乳腺癌风险降低相关，并且最近一项观察性研究发现，使用二甲双胍的糖尿病合并乳腺癌患者病理完全缓解率更高。二甲双胍作为辅助性乳腺癌治疗的正式临床试验已经启动并正在进行。同样，生活方式改变对乳腺癌结局的影响也正在积极研究中。几项生活方式干预研究表明，乳腺癌人群中体重减轻、增加体育活动和饮食改变是可行的，并且乳腺癌诊断后进行生活方式改变的个体在身体和心理方面都有诸多益处。在本文中，作者回顾了将肥胖与乳腺癌风险及结局联系起来的证据，并概述了乳腺癌患者的生活方式干预研究。
