Is leptin a mediator of adverse prognostic effects of obesity in breast cancer?
Is leptin a mediator of adverse prognostic effects of obesity in breast cancer?
复制标题
DOI：
10.1200/jco.2005.02.048
复制
发表时间：
2005-09-01
影响因子：
45.3
通讯作者：
Hood, N
中科院分区：
文献类型：
--
作者：
Goodwin, PJ;Ennis, M;Hood, N
目的瘦素是一种脂肪细胞源性细胞因子，在肥胖症患者中升高，与肿瘤的迁移和侵袭、血管生成增强、致癌作用和芳香化酶活性增加有关。肥胖对乳腺癌患者的预后有不良影响，瘦素可能介导肥胖对乳腺癌患者预后的不良影响。在辅助治疗前采集储存的空腹血标本，测定瘦素。结果患者年龄26 ~ 74岁，T1 = 262例，T2 = 151例，T3 = 23例，TX = 35例，NO = 323例，N1 = 148例。雌激素受体阳性286例，孕激素受体阳性259例。145例患者接受了辅助化疗，146例接受了辅助他莫昔芬，46例接受了两种治疗，134例两种治疗都没有接受。平均瘦素为15.2 +/- 10.1 ng/mL。单变量，瘦素与OS相关（总体P = 0.049;绝经后P = 0.014）。瘦素与DDFS总体或任何绝经亚组均无相关性（P >= .19）。在多变量考克斯模型中，瘦素与DDFS或OS无显著相关性（分别为P = 0.11和0.075）。调整胰岛素或体重指数进一步降低了瘦素与outcome.Conclusion虽然瘦素与肥胖和胰岛素密切相关，我们不能表明，它是独立相关的早期乳腺癌的预后。因为我们不能排除适度的预后影响，我们建议进行更多的研究来探索这种潜在的联系，特别是在绝经后妇女中。
Purpose Leptin, an adipocyte-derived cytokine that is elevated in obesity, has been associated with tumor migration and invasion, enhancement of angiogenesis, and increased carcinogenesis, aromatase activity. It has been suggested that leptin may mediate adverse prognostic effects of obesity in breast cancer.Patients and Methods Four hundred seventy-one women with surgically resected T1-3, N0-1, M0 breast cancer were studied. Leptin was assayed in stored fasting blood specimens obtained before adjuvant therapy. Women were followed prospectively for distant disease-free survival (DDFS) and overall survival (OS).Results Patients ranged from 26 to 74 years of age, and staging was as follows: T1 = 262, T2 = 151, T3 = 23, TX = 35, NO = 323, and N1 = 148. Estrogen receptor was positive in 286 patients, and progesterone receptor was positive in 259 patients. One hundred forty-five patients received adjuvant chemotherapy, 146 received adjuvant tamoxifen, 46 received both, and 134 received neither. Mean leptin was 15.2 +/- 10.1 ng/mL. Univariately, leptin was associated with OS (overall P = .049; P = .014 postmenopausal). Leptin was not associated with DDFS overall or in any menopausal subgroup (P >= .19). In multivariate Cox modeling, leptin was not significantly associated with DDFS or OS (P = .11 and 0.075, respectively). Adjustment for insulin or body mass index further reduced the association of leptin with outcome.Conclusion Although leptin is strongly correlated with obesity and insulin, we could not show that it is independently associated with prognosis in early-stage breast cancer. Because we cannot rule out modest prognostic effects, we recommend additional research to explore this potential association, particularly in postmenopausal women.