Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Carcinoma

Breast Neoplasms

Carcinoma in Situ

Body Weight

Weight Loss

Carcinoma, Ductal

Carcinoma, Intraductal, Noninfiltrating

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Carcinoma In Situ

PRT will be done with resistance bands; participants will receive instruction on three resistance band exercises (triceps, biceps, and shoulder overhead) from an American College of Sports Medicine (ACSM) certified exercise specialist. Participants also will receive dietary counseling from a registered dietitian on correcting nutrient deficiencies that are detected during analysis of their 2-day dietary recalls.

This arm will receive all components of the active comparator arm, plus counseling to achieve a weight loss of 1.5-2 pounds/week. Participants will be trained on how to achieve this caloric deficit through both dietary restriction and increased physical activity. Weight loss will be promoted via a healthy, nutritionally adequate diet consistent with American Cancer Society guidelines. Protein levels will be based on 0.8 g/kg body weight. The distribution of food groups will be customized for preferences. An exercise program will be tailored taking into account kcal expenditure for various activities at a specific body weight; expenditures of 200-400 kcal/day will serve as a goal. Aerobic training of large muscles (legs) will be emphasized to achieve a greater kcal deficit; ramping of intensity and volume over time will be pursued as per the ACSM guidelines. Participants will train once weekly while supervised by an exercise physiologist and daily at home.

no additional information; see arm description

Active Comparator: Progressive Resistance Training (PRT) and a healthy diet

no additional information, see arm description

Experimental: PRT and a healthy diet, plus weight loss

Wendy Demark-Wahnefried, PhD, RD

This pilot/feasibility trial seeks to explore whether an acute bout of negative energy balance prior to surgery affects biomarkers of neoplasia. Forty overweight or obese postmenopausal women diagnosed with ductal carcinoma in situ (DCIS) or early stage breast cancer (Stage I or II) who elect mastectomy or lumpectomy will be randomly assigned 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, Vascular Epithelial Growth Factor (VEGF), Nuclear Factor kappa beta (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. 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 standard therapies.

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), the investigators propose a pilot study that builds on the investigators 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?" The investigators will randomly assign 40 overweight or obese postmenopausal women diagnosed with ductal carcinoma in situ (DCIS) or early stage breast 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, Vascular Epithelial Growth Factor (VEGF), Nuclear Factor kappa beta (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 standard therapies. Thus, the research that is proposed will not only increase the investigators 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, as well as a novel adjunct therapy for women with early stage invasive disease.

Effects of Diet and Exercise on Ductal Carcinoma in Situ

Exploring Effects of Weight Loss on Ductal Carcinoma In Situ

Ki-67 will be used to determine tumor proliferation. Ki-67 is a cancer antigen that is found in growing, dividing cells but is absent in the resting phase of cell growth. This characteristic makes Ki-67 a good tumor marker. This test is done on a sample of tumor tissue, to help predict prognosis. High levels of Ki-67 indicate an aggressive tumor and predict a poor prognosis. High scores mean that the cancer cells are growing and dividing at a rapid pace. The Ki-67 scores will be compared between arms.

Enroll 40 subjects within 2-year study, retain \>80% of the sample and completion \>70% of contact sessions.

Tumor Markers on the CHIEF (Convergence of Hormonal, Inflammatory and Energy-related Factors) Pathway, e.g., Insulin Receptor, Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor alpha (TNF-alpha), Nuclear Factor Kappa Beta (NFKB), caspase-3, as well as various phosphoproteins.

Insulin, leptin, Sex Hormone Binding Globulin, VEGF, TNF-alpha

Select genes on the CHIEF pathway as well as \~47,231 curated and putative genes and expressed sequence tags (ESTs)

24-hour recalls to assess kcal intake as well as intake of fat, protein, and carbohydrate and diet quality

Assessed via accelerometry as well as via questionnaire

Sub-maximal testing and a modified version of the Naughton Protocol

Spots Global Cancer Trial Database for experimental: prt and a healthy diet, plus weight loss