Effects of Diet and Exercise on Ductal Carcinoma in Situ

Breast Cancer Clinical Trial

— DCIS  

Official title:

Exploring Effects of Weight Loss on Ductal Carcinoma In Situ

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02224807
• Other study ID #: R21CA178359-01A1
• Status: Completed
• Phase: N/A
• Start date: July 2014
• Est. completion date: July 2018

Study information

• Verified date: August 2018
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Intraductal, Noninfiltrating
• Ductal Carcinoma In Situ

Intervention

Behavioral:
• 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
no additional information, see arm description

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor proliferation	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.	Baseline to Time of Surgery
Primary	Weight		Baseline to Time of Surgery
Primary	Feasibility	Enroll 40 subjects within 2-year study, retain >80% of the sample and completion >70% of contact sessions.	Baseline to Time of Surgery
Secondary	Body Composition	Via Dual Energy Absorptiometry (DXA)	Baseline to Time of Surgery
Secondary	Waist Circumference		Baseline to Time of Surgery
Secondary	Tumor markers	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.	Baseline to Time of Surgery
Secondary	Serum Biomarkers	Insulin, leptin, Sex Hormone Binding Globulin, VEGF, TNF-alpha	Baseline to Time of Surgery
Secondary	Gene expression	Select genes on the CHIEF pathway as well as ~47,231 curated and putative genes and expressed sequence tags (ESTs)	Baseline to Time of Surgery
Secondary	Dietary Intake	24-hour recalls to assess kcal intake as well as intake of fat, protein, and carbohydrate and diet quality	Baseline to Time of Surgery
Secondary	Physical Activity	Assessed via accelerometry as well as via questionnaire	Baseline to Time of Surgery
Secondary	Quality of Life	Using the FACT-B	Baseline to Time of Surgery
Secondary	Cardiorespiratory Fitness	Sub-maximal testing and a modified version of the Naughton Protocol	Baseline to Time of Surgery