Effects of Diet and Exercise on Ductal Carcinoma in Situ

NCT02224807 | Completed DMC

• 1 other identifier: R21CA178359-01A1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Ductal Carcinoma In Situ; Breast Cancer

Keywords

breast cancer; diet; exercise; weight loss

Outcome Measures

Primary Outcomes (3)

• 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

• Weight

  Baseline to Time of Surgery

• 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 Outcomes (9)

• Body Composition

  Baseline to Time of Surgery

• Waist Circumference

  Baseline to Time of Surgery

• Tumor markers

  Baseline to Time of Surgery

• Serum Biomarkers

  Baseline to Time of Surgery

• Gene expression

  Baseline to Time of Surgery

Study Arms (2)

Progressive Resistance Training (PRT) and a healthy diet

ACTIVE COMPARATOR

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.

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

PRT and a healthy diet, plus weight loss

EXPERIMENTAL

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.

Behavioral: Experimental: PRT and a healthy diet, plus weight loss

Interventions

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

no additional information; see arm description

Also known as: Diet; Exercise; Physical activity

Progressive Resistance Training (PRT) and a healthy diet

Experimental: PRT and a healthy diet, plus weight loss BEHAVIORAL

no additional information, see arm description

Also known as: Diet; Exercise, Physical Activity

PRT and a healthy diet, plus weight loss

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (3)

• Smith KS, Fruge AD, van der Pol W, Caston NE, Morrow CD, Demark-Wahnefried W, Carson TL. Gut microbial differences in breast and prostate cancer cases from two randomised controlled trials compared to matched cancer-free controls. Benef Microbes. 2021 Jun 15;12(3):239-248. doi: 10.3920/BM2020.0098. Epub 2021 Apr 1.

  PMID: 33789551 DERIVED

• Fruge AD, Van der Pol W, Rogers LQ, Morrow CD, Tsuruta Y, Demark-Wahnefried W. Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial. J Acad Nutr Diet. 2020 Apr;120(4):650-659. doi: 10.1016/j.jand.2018.08.164. Epub 2018 Nov 9.

  PMID: 30420171 DERIVED

• Tsuruta Y, Rogers LQ, Krontiras H, Grizzle WE, Fruge AD, Oster RA, Umphrey HR, Jones LW, Azrad M, Demark-Wahnefried W. Exploring effects of presurgical weight loss among women with stage 0-II breast cancer: protocol for a randomised controlled feasibility trial. BMJ Open. 2016 Sep 15;6(9):e012320. doi: 10.1136/bmjopen-2016-012320.

  PMID: 27633639 DERIVED

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Breast Neoplasms; Motor Activity; Weight Loss

Interventions

Hypoxanthine Phosphoribosyltransferase; Diet; Exercise

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Behavior; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pentosyltransferases; Glycosyltransferases; Transferases; Enzymes; Enzymes and Coenzymes; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Wendy Demark-Wahnefried, PhD, RD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 25, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: August 31, 2018

Record last verified: 2018-08

Locations

US (1)