Effects of Diet and Exercise on Ductal Carcinoma in Situ

Not Applicable

Completed

• Conditions: Ductal Carcinoma In Situ; Breast Cancer

• Registration Number: NCT02224807
• Lead Sponsor: University of Alabama at Birmingham

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 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.

Detailed Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-08-19
• Study First Submitted QC: 2014-08-21
• Study First Posted: 2014-08-25
• Primary Completion: 2018-07
• Study Completion: 2018-07
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-29
• Last Update Posted: 2018-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 32

Inclusion Criteria

• Postmenopausal women with intermediate-to-high nuclear grade DCIS or stage I or II breast cancer who elect surgery and who have >3-week lag-time between the start of the intervention and their scheduled surgery;
• Overweight or obese (BMI:25-60);
• English speaking/reading
• Willing to be assigned to either study arm

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Exclusion Criteria

• Have a pre-existing medical condition(s) that preclude adherence to unsupervised exercise;
• Have a current medical condition that affects weight status;
• Has an active malignancy, other than DCIS, invasive breast cancer, or non-melanoma skin cancer;
• Currently enrolled in a weight loss program
• Have received or scheduled to receive neoadjuvant chemotherapy prior to mastectomy or lumpectomy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Tumor proliferation	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.
Feasibility	Baseline to Time of Surgery	Enroll 40 subjects within 2-year study, retain \>80% of the sample and completion \>70% of contact sessions.
Weight	Baseline to Time of Surgery

Secondary Outcome Measures

Name	Time	Method
Body Composition	Baseline to Time of Surgery	Via Dual Energy Absorptiometry (DXA)
Cardiorespiratory Fitness	Baseline to Time of Surgery	Sub-maximal testing and a modified version of the Naughton Protocol
Waist Circumference	Baseline to Time of Surgery
Serum Biomarkers	Baseline to Time of Surgery	Insulin, leptin, Sex Hormone Binding Globulin, VEGF, TNF-alpha
Tumor markers	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.
Gene expression	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	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	Baseline to Time of Surgery	Assessed via accelerometry as well as via questionnaire
Quality of Life	Baseline to Time of Surgery	Using the FACT-B

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States