Hormones During Weight Loss in Breast Cancer Survivors

描述(由申请人提供) 超重或肥胖是绝经前和绝经后乳腺癌的一个公认的负面预后因素，已经提出了几种机制来解释这一观察结果。一个可能的机制与过量的脂肪组织对循环性腺激素的影响有关，因为脂肪组织是性腺外雌激素的重要来源，来自前体肾上腺雄激素。肥胖与绝经后妇女血液中雌酮和雌二醇浓度的升高有关，也与性激素结合球蛋白(SHBG)水平降低有关，性激素结合球蛋白(SHBG)水平增加了生物可利用的雌激素成分。另一种可能的机制与胰岛素和胰岛素样生长因子(IGF-I)有关，这些因素与肥胖和体重的相互作用与乳腺癌幸存者的肥胖程度高度相关。在一项由NCI资助的随机对照研究中，我们正在测试一项多成分减肥计划对超重和肥胖乳腺癌幸存者(n=85)体重和身体成分变化的影响。并在基线、16周(在强化治疗阶段之后)和一年从研究参与者那里采集血样。干预包括认知行为疗法，增加体力活动以促进保持(或增加)瘦体重，调整饮食以促进能量失衡，以及改善身体形象和自我接纳的策略。拟议的小额赠款项目的目的是(1)利用登记时和参与后收集的储存血液样本，对参加减肥计划的乳腺癌幸存者(与等待名单对照组中的妇女相比)进行SHBG和血清雌激素的实验室分析，并检查干预对这些激素因素的影响；以及(2)进行血清胰岛素、总IGF-I、游离IGF-I的实验室分析。和一个关键的结合蛋白(IGFBP-3)，并检验参与该计划的乳腺癌幸存者(与等待名单对照组中的女性相比)对这些激素因素的干预效果，使用登记时和参与后收集的储存血液样本，测量荷尔蒙因素和本项目中分析的数据，将提供有关这些荷尔蒙因素对体重减轻的反应和超重和肥胖乳腺癌幸存者的身体成分变化的重要信息。此外，这项研究的结果将为超重或肥胖影响已被诊断为乳腺癌的女性的预后的可能机制提供有价值的见解。

DESCRIPTION (provided by applicant) Overweight or obesity is an established negative prognostic factor in both pre-menopausal and postmenopausal breast cancer, and several mechanisms have been proposed to explain this observation. One possible mechanism relates to the effect of excess adipose tissue on circulating gonadal hormones, because adipose tissue is an important extragonadal source of estrogens from precursor adrenal androgens. Obesity is associated with increased circulating concentrations of estrone and estradiol in postmenopausal women, and it also is associated with decreased levels of sex-hormone binding globulin (SHBG), which increases the bioavailable estrogen fraction Another possible mechanism relates to insulin and insulin-like growth factor (IGF)-I, and the interactions of these factors with adiposity and weight Circulating insulin concentration is highly correlated with degree of adiposity in breast cancer survivors In an ongoing NCI-funded randomized controlled study, we are testing the effect of a multi-component weight reduction program on change in body weight and body composition in overweight and obese breast cancer survivors (n=85), and blood samples are collected from the study participants at baseline, 16 weeks (after the intensive treatment phase), and one year. The intervention incorporates cognitive-behavioral therapy, increased physical activity to promote maintenance of (or increased) lean body mass, diet modification to facilitate an energy imbalance, and strategies to improve body image and self-acceptance. The aims of the proposed small grant project are (1) To conduct laboratory assays of SHBG and serum estrogens, and to examine the effect of the intervention on these hormonal factors, in breast cancer survivors participating in a weight reduction program (compared to women in a wait-list control group), using stored blood samples collected at enrollment and following participation, and (2) To conduct laboratory assays of serum insulin, total IGF-I, free IGF-I, and a key binding protein (IGFBP-3) and to examine the effect of the intervention on these hormonal factors in breast cancer survivors participating in the program (compared to women in a wait-list control group), using stored blood samples collected at enrollment and following participation The measurement of hormonal factors and data analyzed in this project will provide vital information about the responsiveness of these hormonal factors to weight loss and change in body composition in overweight and obese breast cancer survivors Also, the results from this study will provide valuable insight about possible mechanisms by which overweight or obesity influences prognosis in women who have been diagnosed with breast cancer.