Exploring Effects of Weight Loss on Ductal Carcinoma In Situ

探索减肥对导管原位癌的影响

基本信息

批准号：
8701513
负责人：
Wendy Demark-Wahnefried
金额：
$ 15.99万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8701513
关键词：
Acute Adherence Affect American Angiogenic Factor Animals Apoptosis Attention Behavior Therapy Biological Biological Markers Biometry Biopsy Blood Body Weight Body Weight decreased Body mass index Breast Caloric Restriction Cancer Biology Cancer Prognosis Cancer Survivor Cells Characteristics Clinical Consent Control Groups Counseling Data Diagnosis Diet Disease Duct (organ) structure Economic Burden Energy Intake Energy Metabolism Enrollment Environment Estradiol Exercise Exhibits Exposure to Flax Gene Expression Health Hormonal Hormones Human Incidence Inflammation Instruction Insulin Insulin Receptor Intervention Intervention Studies Ipsilateral Lead Link Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate Malnutrition Mammary Gland Parenchyma Mastectomy Measures Menopause Modeling Molecular Profiling Monitor Morbidity - disease rate National Comprehensive Cancer Network Neoplasms Noninfiltrating Intraductal Carcinoma Nutrient Obesity Operative Surgical Procedures Outcome Overweight Participant Pathology Pathway interactions Patients Peripheral Blood Mononuclear Cell Phase Phosphoproteins Physical activity Pilot Projects Postmenopause Precancerous Conditions Proto-Oncogene Proteins c-akt Quality of life Randomized Randomized Controlled Trials Regimen Research Risk Factors Sampling Serum Sex Hormone-Binding Globulin Speed Supplementation Surgical Models TNF gene Time Tissues Tumor Biology Tumor Markers Tumor Tissue Vascular Endothelial Growth Factors Weight Woman Work arm base biobehavior breast lumpectomy cytokine density diet and exercise dietary restriction energy balance fitness group intervention improved leptin receptor malignant breast neoplasm mortality nutrition post intervention preclinical study prevent public health relevance response standard of care strength training success translational study trend tumor tumor growth tumor progression waist circumference

项目摘要

DESCRIPTION (provided by applicant): Obesity is a known risk factor for invasive breast cancers that occur post-menopause. Obese women also die twice as frequently from breast cancer than those of normal weight. Numerous preclinical studies show the benefits of caloric restriction on cancer progression in animals - but, will similar effects be seen in humans? In response to a call for translational studies that will identify biological/biobehavioral pathways through which weight loss may affect cancer prognosis (PAR-12-229), we propose a pilot study that builds on our success of pre-surgical interventions to answer the research question, "does negative energy balance with concomitant weight loss invoke anti-cancer effects on tumor biology and the host environment?" We will randomly assign 40 overweight or obese postmenopausal women diagnosed with ductal carcinoma in situ (DCIS) (a precursor to invasive cancer) who elect mastectomy or lumpectomy to 1-of-2 study arms: 1) an Attention Control Group that receives instruction on dietary approaches to correct nutritional deficiencies and progressive resistance training (PRT) that targets the arm ipsilateral to the affected breast; or 2 an Experimental Group that will receive PRT and guidance to correct nutritional deficiencies plus an intensive intervention to promote a 1.5-2 pound/week weight loss through diet, exercise, and behavior modification. This study will explore and contrast changes in body mass index (BMI) observed from enrollment to the time of surgery in the experimental vs. attention control arms, and also monitor changes in energy intake and physical activity. These changes will be studied in relation to the following endpoints: a) changes in select circulating biomarkers and gene expression related to cancer progression, hormonal status, inflammation and other energy-related factors; b) rates of tumor proliferation and apoptosis; c) tumor markers, e.g., insulin receptor, VEGF, AKT, NFkB, and phosphoproteins associated with the Convergence of Hormones, Inflammation and Energy-Rated Factors (CHIEF) pathway; and d) functional and health-related outcomes. Because both tumor tissue and blood will be examined from pre-to-post-intervention, this study will provide exciting new data that can elucidate pathways by which energy balance affects breast cancer progression from a non-invasive to an invasive state. Although longer term weight loss is recommended for overweight and obese breast cancer survivors, it is not known whether placing the body in a state of negative energy balance will have a favorable impact on the tumor. If beneficial changes in tumor biology and the host environment occur with short-term, pre-surgical weight loss, this study provides proof of concept that weight loss may offer an acceptable and complementary treatment option that could be combined with active surveillance for longer term management. Thus, the research that is proposed will not only increase our understanding of the impact of negative energy balance on tumor biology, but could change the standard of care and offer a more conservative treatment option for the 50,000 American women who are diagnosed with DCIS each year.

描述（由申请人提供）：肥胖是侵入性乳腺癌的已知危险因素。肥胖的妇女也死于乳腺癌的频率是正常体重的两倍。许多临床前研究表明，热量限制对动物癌症进展的好处 - 但是，在人类中会看到类似的影响吗？ In response to a call for translational studies that will identify biological/biobehavioral pathways through which weight loss may affect cancer prognosis (PAR-12-229), we propose a pilot study that builds on our success of pre-surgical interventions to answer the research question, "does negative energy balance with concomitant weight loss invoke anti-cancer effects on tumor biology and the host environment?" We will randomly assign 40 overweight or obese postmenopausal women diagnosed with ductal carcinoma in situ (DCIS) (a precursor to invasive cancer) who elect mastectomy or lumpectomy to 1-of-2 study arms: 1) an Attention Control Group that receives instruction on dietary approaches to correct nutritional deficiencies and progressive resistance training (PRT) that targets the arm ipsilateral to the affected 胸部;或2一个实验组，将获得PRT和指导，以纠正营养缺乏症，并采取强化干预措施，以通过饮食，运动和行为修改来促进1.5-2磅/周的体重减轻。这项研究将探索和对比度的变化体重指数（BMI）从入学到实验与注意力控制臂的手术时间观察到的，并监测能量摄入和体育活动的变化。这些变化将与以下终点有关：a）与癌症进展，荷尔蒙状态，炎症和其他能量相关因素有关的选择循环生物标志物和基因表达的变化； b）肿瘤增殖和凋亡率； c）肿瘤标记，例如胰岛素受体，VEGF，AKT，NFKB和磷蛋白与激素，炎症和能量评分因子（主要）途径相关的磷酸蛋白； d）功能和健康相关的结果。由于肿瘤组织和血液都将从预干预前进行检查，因此这项研究将提供令人兴奋的新数据，这些数据可以阐明能量平衡影响从非侵入性到侵入性状态的乳腺癌进展的途径。尽管建议对超重和肥胖的乳腺癌幸存者进行长期体重减轻，但尚不知道将身体处于负能量平衡状态是否会对肿瘤产生有利的影响。如果肿瘤生物学和宿主环境的有益变化发生在短期，手术前的体重减轻，这项研究提供了概念证明，即减肥可能会提供可接受的补充治疗方案，可以将其与长期管理的主动监视结合使用。因此，提出的研究不仅会增加我们对负能量平衡对肿瘤生物学的影响的理解，而且可以改变护理标准，并为每年被诊断出患有DCI的50,000名美国女性提供更保守的治疗选择。