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既定的负面预后因素，已经提出了几种机制来解释这一观察结果。 一种可能的机制与过量脂肪组织对循环性腺激素的影响有关，因为脂肪组织是来自前体肾上腺雄激素的雌激素的重要性腺外来源。肥胖与绝经后妇女中雌酮和雌二醇的循环浓度增加有关，并且还与性激素结合球蛋白（SHBG）水平降低有关，这增加了生物可利用的雌激素部分。另一种可能的机制涉及胰岛素和胰岛素样生长因子（IGF）-I，以及这些因素与肥胖和体重的相互作用。循环胰岛素浓度与乳腺癌幸存者的肥胖程度高度相关。资助的随机对照研究，我们正在测试多组分减肥计划对超重和肥胖乳腺癌幸存者（n=85）的体重和身体组成变化的影响，并在基线、16周（强化治疗阶段后）和一年时从研究参与者收集血液样品。 干预措施包括认知行为疗法，增加身体活动以促进维持（或增加）瘦体重，饮食调整以促进能量失衡，以及改善身体形象和自我接受的策略。 拟议的小额赠款项目的目的是（1）在参加减肥计划的乳腺癌幸存者中进行SHBG和血清雌激素的实验室测定，并检查干预对这些激素因子的影响（与等待名单对照组中的女性相比），使用在入组时和参与后收集的储存血液样本，以及（2）对参与该计划的乳腺癌幸存者进行血清胰岛素、总IGF-I、游离IGF-I和关键结合蛋白（IGFBP-3）的实验室测定，并检查干预对这些激素因子的影响（与等待名单对照组中的女性相比），使用在招募时和参与后收集的储存血液样本。本项目中分析的激素因素和数据的测量将提供有关这些激素因素对以下因素的反应性的重要信息：超重和肥胖乳腺癌幸存者的体重减轻和身体成分的变化此外，这项研究的结果将为超重或肥胖影响乳腺癌患者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.