Influence of Exercise and Adiposity on Biomarkers of Breast Cancer Recurrence

描述（由申请人提供）：由于检测和治疗的进步，乳腺癌（BC）的生存率在过去二十年中稳步提高。观察性研究表明，如果乳腺癌幸存者（BCS）能够充分锻炼身体并控制体重，预后可能会进一步改善。虽然这些观察结果令人鼓舞，但体力活动（PA）对BC生存的这种保护作用的原因仍将是推测性的，直到建立解释这种联系的生物学机制。同样重要的是确定PA是否必须减少体内脂肪储存以发挥保护作用。在缺乏以生存期为终点的对照临床试验的情况下，提供癌症进展生物标志物数据的运动研究可以证实流行病学报告，并产生关于运动和体脂对BC生存期作用的新知识。本研究的目的是确定运动和体脂变化对与BCS癌症进展相关的3种生物标志物（性和代谢激素以及脂肪细胞因子）的影响。我们储存了3组绝经后BCS患者的血清样本，这些患者参加了以身体成分和身体功能为主要终点的抗阻运动对照试验。我们将分析来自BCS的基线和干预后样本，这些BCS参与了1年的阻力训练或1年的坐姿拉伸运动（对照条件），以获得3种类型的癌症进展标志物。该研究的具体目的是：1）确定抗阻运动对癌症进展标志物的影响，2）确定肥胖的变化是否介导癌症进展标志物的变化。拟议的研究是创新的，因为它将是第一项结合来自参与类似干预的3个BCS队列的联合收割机数据的研究，以确定力量训练对与BC进展相关的3种生物标志物的影响。这项研究也将是第一个考虑抗阻运动是否必须减少脂肪量才能出现生物标志物变化的研究。该R21应用程序符合PA-09-149的目标，要求对存储的生物样本进行新的分析，以测试新的假设，这些假设将产生关于能量平衡，癌症预后和生活质量之间关系的知识。该应用程序还解决了NCI的能量学和癌症（TREC）倡议的跨学科研究的主要目标，以更好地了解整个癌症连续体的能量平衡和致癌之间的关联机制。这项研究与公共卫生有关，因为BC是女性的主要癌症，与其他女性相比，BCS患新BC的风险高出67%。这项研究意义重大，因为临床医生和患者都需要获得基于证据的低成本策略，以降低BCS复发风险并改善生活质量。如果拟议研究的目的得以实现，这项研究的结果将产生关于最有可能改善生存结果的运动干预的类型和设计的新知识。 公共卫生相关性：这项研究与公共卫生有关，因为乳腺癌是女性的主要癌症，迫切需要改善乳腺癌幸存者生存和生活质量的策略。这项拟议中的研究将确定运动是否会减少与乳腺癌复发相关的生物标志物。

DESCRIPTION (provided by applicant): Survival rates for breast cancer (BC) have steadily improved over the past two decades because of advances in detection and treatment. Observational studies suggest that if breast cancer survivors (BCS) can become sufficiently physically active and control their weight, prognosis may improve even further. While these observational findings are encouraging, the reasons for this protective effect of physical activity (PA) on BC survival will remain speculative until a biologic mechanism(s) that explains this link is established. Equally important is to establish whether or not PA must decrease body fat stores in order to exert a protective effect. In the absence of controlled clinical trials with survival as an endpoint, exercise studies that provide data on biomarkers of cancer progression can substantiate epidemiologic reports and generate new knowledge about the role of exercise and body fat on BC survival. The purpose of the proposed study is to determine the influence of exercise and body fat changes on 3 types of biomarkers (sex and metabolic hormones and adipocytokines) associated with cancer progression in BCS. We have stored serum samples from 3 cohorts of postmenopausal BCS who participated in controlled trials of resistance exercise with primary endpoints of body composition and physical function. We will analyze baseline and post-intervention samples from BCS who participated in either 1 year of resistance training or 1 year of seated stretching exercise (control condition) for 3 types of cancer progression markers. The specific aims of the study are to: 1) determine the influence of resistance exercise on markers of cancer progression and 2) determine whether or not changes in adiposity mediate changes in cancer progression markers. The proposed study is innovative because it will be the first study to combine data from 3 cohorts of BCS participating in similar interventions in order to determine the effects of strength training on 3 types of biomarkers associated with BC progression. The study will also be the first to consider whether or not resistance exercise must reduce fat mass in order for changes in biomarkers to emerge. This R21 application matches the objectives of PA-09-149 calling for new analyses of stored biologic samples to test new hypotheses that will generate knowledge about the relationships among energy balance, cancer prognosis and quality of life. The application also addresses a primary goal of the NCI's Transdisciplinary Research on Energetics and Cancer (TREC) initiative to better understand the mechanisms underlying the association between energy balance and carcinogenesis across the cancer continuum. This study is relevant to public health because BC is the leading cancer in women and BCS have a 67% greater risk of developing a new BC compared to the other women. This research is significant because both clinicians and patients need access to evidence-based, low-cost strategies for lowering risk of recurrence and improving quality of life for BCS. If the aims of the proposed study are achieved, findings from this study will generate new knowledge about the type and design of exercise interventions most likely to improve survival outcomes. PUBLIC HEALTH RELEVANCE: This study is relevant to public health because breast cancer is the leading cancer in women and strategies that improve both survival and quality of life for breast cancer survivors are urgently needed. The proposed study will determine whether exercise reduces biological markers associated with breast cancer recurrence.