Clinical Trial: Effects of Diet and Exercise on Ductal Carcinoma in Situ

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Exploring Effects of Weight Loss on Ductal Carcinoma In Situ

Brief Summary: 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 fav

Detailed Summary: 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 G
Sponsor: University of Alabama at Birmingham

Current Primary Outcome:

  • Tumor proliferation [ Time Frame: Baseline to Time of Surgery ]
    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.
  • Weight [ Time Frame: Baseline to Time of Surgery ]
  • Feasibility [ Time Frame: Baseline to Time of Surgery ]
    Enroll 40 subjects within 2-year study, retain >80% of the sample and completion >70% of contact sessions.


Original Primary Outcome:

  • Tumor proliferation [ Time Frame: Baseline to Time of Surgery ]
    Ki67
  • Weight [ Time Frame: Baseline to Time of Surgery ]
  • Feasibility [ Time Frame: Baseline to Time of Surgery ]
    Enroll 40 subjects within 2-year study, retain >80% of the sample and completion >70% of contact sessions.


Current Secondary Outcome:

  • Body Composition [ Time Frame: Baseline to Time of Surgery ]
    Via Dual Energy Absorptiometry (DXA)
  • Waist Circumference [ Time Frame: Baseline to Time of Surgery ]
  • Tumor markers [ Time Frame: Baseline to Time of Surgery ]
    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.
  • Serum Biomarkers [ Time Frame: Baseline to Time of Surgery ]
    Insulin, leptin, Sex Hormone Binding Globulin, VEGF, TNF-alpha
  • Gene expression [ Time Frame: Baseline to Time of Surgery ]
    Select genes on the CHIEF pathway as well as ~47,231 curated and putative genes and expressed sequence tags (ESTs)
  • Dietary Intake [ Time Frame: Baseline to Time of Surgery ]
    24-hour recalls to assess kcal intake as well as intake of fat, protein, and carbohydrate and diet quality
  • Physical Activity [ Time Frame: Baseline to Time of Surgery ]
    Assessed via accelerometry as well as via questionnaire
  • Quality of Life [ Time Frame: Baseline to Time of Surgery ]
    Using the FACT-B
  • Cardiorespiratory Fitness [ Time Frame: Baseline to Time of Surgery ]
    Sub-maximal testing and a modified version of the Naughton Protocol


Original Secondary Outcome: Same as current

Information By: University of Alabama at Birmingham

Dates:
Date Received: August 19, 2014
Date Started: July 2014
Date Completion: June 2017
Last Updated: January 17, 2017
Last Verified: January 2017