Energy Balance and Breast Cancer Aspects-II (EBBA-II)

• ClinicalTrials.gov Identifier: NCT02240836
• Recruitment Status: Active, not recruiting
• First Posted: September 16, 2014
• Last Update Posted: April 26, 2021
• Sponsor: Oslo University Hospital
• Collaborators: St. Olavs Hospital; The Research Council of Norway
• Information provided by (Responsible Party): Inger Thune, Oslo University Hospital

Study Description

Brief Summary:

The purpose of this study, the EBBA-II trial, is to determine whether a 12 month exercise program comprised of strength and endurance training among newly diagnosed breast cancer patients undergoing adjuvant therapy, will influence cardiopulmonary function. Secondary aims are to determine whether the 12 month exercise program will influence factors associated with metabolic profile, tumor growth, disease-free survival, overall mortality and breast cancer specific mortality. Furthermore, the effect on QoL parameters, and dietary factors will be assessed and evaluated.

Condition or disease	Intervention/treatment	Phase
DCIS Grade 3; Stage I Breast Cancer; Stage II Breast Cancer; LCIS, Lobular Carcinoma in Situ	Other: Intervention. Exercise	Not Applicable

Detailed Description:

The EBBA (Energy Balance and Breast cancer Aspects)-II study is a randomized clinical 12 month physical activity intervention trial, including female breast cancer patients diagnosed with histologically verified invasive cancer stage I-II or carcinoma in situ (DCIS/LCIS) grade 3.

• Participants are randomized to either control or intervention group 10 days +/- 2 days after surgery. The intervention start 3 weeks after surgery and continue throughout adjuvant treatments given (chemotherapy, radiation, endocrine therapy etc). The intervention group receive a detailed training program based on their own ventilatory maximal oxygen consumption (VO2max) at baseline. They meet for supervised training sessions in groups for 60 minutes x 2/ week during 12 months. In addition, they are informed to exercise at home for at least of total 120 minutes weekly aiming to perform a total of 240 minutes exercise, weekly. The patients in the control group receive standard of care without any restrictions regarding exercise.
• All participants will undergo a series of measurements before surgery, after surgery, 6 months and after the 12 months exercise intervention trial. Clinical measurements will include anthropometric measurements, fasting blood, fecal and urine samples and cardiopulmonary exercise test (CPET). Complete questionnaires (food diary (PFD)/food frequency questionnaires (FFQ), quality of life (QoL)).
• All participants will come to clinical examination and fasting blood sampling after 2, 3, 5 and 10 years follow up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 545 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Energy Balance and Breast Cancer Aspects-II Study
• Actual Study Start Date: September 2014
• Actual Primary Completion Date: October 31, 2017
• Estimated Study Completion Date: October 31, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention. Exercise; The intervention starts 3-4 weeks after surgical treatment. The exercise program is performed in parallel with standard breast cancer treatment, and take place in supervised exercise groups by experienced physiotherapists. The duration of the intervention exercise program is 12 months, and the participants will attend the exercise groups for training 60 minutes twice a week. Additionally, they will exercise at home for at least 120 minutes a week, aiming to perform a total of 240 minutes of exercise per week	Other: Intervention. Exercise; Physical activity. Attendance in exercise groups 60 min. twice a week and exercise at home 120 min per week. Intervention for 12 months.; Other Name: Physical activity
No Intervention: Control group; Control group, standard treatment regimen

Outcome Measures

Primary Outcome Measures :

1. VO2max [ Time Frame: Baseline,12 months ]
   Change in VO2max from baseline to 12 months

Secondary Outcome Measures :

1. BMI [ Time Frame: Baseline,12 months ]
   Change in BMI from baseline to 12 months
2. Systolic blood pressure [ Time Frame: Baseline,12 months ]
   Change in systolic blood pressure from baseline to 12 months
3. Diastolic blood pressure [ Time Frame: Baseline,12 months ]
   Change in diastolic blood pressure from baseline to 12 months
4. Total cholesterol [ Time Frame: Baseline,12 months ]
   Change in total cholesterol from baseline to 12 months
5. LDL cholesterol [ Time Frame: Baseline,12 months ]
   Change in LDL cholesterol from baseline to 12 months
6. HDL cholesterol [ Time Frame: Baseline,12 months ]
   Change in HDL cholesterol from baseline to 12 months
7. Total cholesterol/HDL cholesterol [ Time Frame: Baseline,12 months ]
   Change in total cholesterol/HDL cholesterol from baseline to 12 months
8. HbA1c [ Time Frame: Baseline,12 months ]
   Change in concentrations of HbA1c from baseline to 12 months
9. Insulin [ Time Frame: Baseline,12 months ]
   Change in concentrations of blood insulin levels (µIU/mL) from baseline to 12 months
10. Triglycerides [ Time Frame: Baseline,12 months ]
    Change in concentrations of triglycerides from baseline to 12 months
11. C-reactive Protein (CRP) [ Time Frame: Baseline,12 months ]
    Change in concentrations of CRP (mg/L) from baseline to 12 months
12. Heart rate [ Time Frame: Baseline,12 months ]
    Change in heart rate from baseline to 12 months
13. Total fat [ Time Frame: Baseline,12 months ]
    Change in total fat from baseline to 12 months
14. Truncated fat [ Time Frame: Baseline,12 months ]
    Change in truncated fat from baseline to 12 months
15. Waist circumference [ Time Frame: Baseline,12 months ]
    Change in waist circumference from baseline to 12 months
16. Energy from food diary [ Time Frame: Baseline,12 months ]
    Change in energy from food diary from baseline to 12 months
17. Metabolic syndrome [ Time Frame: 12 months ]
    Dichotomous outcome (yes/no)

Other Outcome Measures:

1. Respiratory Quotient (RQ) [ Time Frame: 12 months ]
   Ratio between the amount of CO2 produced in metabolism and O2 used
2. Lactate [ Time Frame: 12 months ]
   Blood lactate from fingertip one minute after test
3. HRmax [ Time Frame: 12 months ]
   Maximal heart rate
4. BORGmax [ Time Frame: 12 months ]
   Subjective measure of exhaustion
5. Disease-free survival [ Time Frame: Baseline, 1 year, 2 years, 5 years, 10 years ]
   Time from baseline to the date of cancer symptoms or death
6. Overall mortality [ Time Frame: Baseline, 1 year, 2 years, 5 years, 10 years ]
   Time from baseline until the date of death, regardless of the cause of death
7. Breast cancer-specific mortality [ Time Frame: Baseline, 1 year, 2 years, 5 years, 10 years ]
   Time from baseline until the date of breast cancer-specific death
8. Other exploratory [ Time Frame: 12 months ]

   Forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), diffusing capacity of the lung for carbon monoxide (DLco)

   Inflammatory markers, prothrombotic markers, urinary markers, adipokines

   Levels of sex steroid hormones

   Growth factors (Insulin-like growth factor [IGF], insulin, insulin-like growth factor binding protein [IGFBP])

   Microenvironment of the breast, tumor infiltrating lymphocytes (TILS), Crown like structures (CLS)

   Microbiota

   Quality of life and dietary factors

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 18-75 years
• Newly diagnosed DCIS grade 3 or invasive breast cancer stage I, II, histologically verified.
• All ethnic groups, but participants have to speak and write the Norwegian language.
• Ability to join and maintain an intervention for 12 months

Exclusion Criteria:

• Verified heart disease
• Dysregulated diabetes mellitus or thyroid disorders
• Muscular and skeletal or other disorders excluding regular physical activity performance
• Body Mass Index >40 kg/m2
• Previous surgical treatment for obesity
• Travel distance >1.5 hour from home to study site

Contacts and Locations

Locations

Norway

Oslo University Hospital

Oslo, Norway

St. Olavs Hospital

Trondheim, Norway, 7000

Sponsors and Collaborators

Oslo University Hospital

St. Olavs Hospital

The Research Council of Norway

Investigators

• Principal Investigator: Inger Thune, MD. PhD; The Department of Oncology, Ullevål, Oslo University Hospital

  Study Documents (Full-Text)

Documents provided by Inger Thune, Oslo University Hospital:

Statistical Analysis Plan  [PDF] April 20, 2021

More Information

Publications:

Thune I, Njolstad I, Lochen ML, Forde OH. Physical activity improves the metabolic risk profiles in men and women: the Tromso Study. Arch Intern Med. 1998 Aug 10-24;158(15):1633-40. doi: 10.1001/archinte.158.15.1633. Erratum In: Arch Intern Med 1998 Jan 11;159(1):17.

Irwin ML, Yasui Y, Ulrich CM, Bowen D, Rudolph RE, Schwartz RS, Yukawa M, Aiello E, Potter JD, McTiernan A. Effect of exercise on total and intra-abdominal body fat in postmenopausal women: a randomized controlled trial. JAMA. 2003 Jan 15;289(3):323-30. doi: 10.1001/jama.289.3.323.

Furberg AS, Veierod MB, Wilsgaard T, Bernstein L, Thune I. Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk. J Natl Cancer Inst. 2004 Aug 4;96(15):1152-60. doi: 10.1093/jnci/djh216.

Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; American Heart Association; National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004 Jan 27;109(3):433-8. doi: 10.1161/01.CIR.0000111245.75752.C6. No abstract available.

Courneya KS, Segal RJ, McKenzie DC, Dong H, Gelmon K, Friedenreich CM, Yasui Y, Reid RD, Crawford JJ, Mackey JR. Effects of exercise during adjuvant chemotherapy on breast cancer outcomes. Med Sci Sports Exerc. 2014 Sep;46(9):1744-51. doi: 10.1249/MSS.0000000000000297.

Friedenreich CM, Woolcott CG, McTiernan A, Ballard-Barbash R, Brant RF, Stanczyk FZ, Terry T, Boyd NF, Yaffe MJ, Irwin ML, Jones CA, Yasui Y, Campbell KL, McNeely ML, Karvinen KH, Wang Q, Courneya KS. Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women. J Clin Oncol. 2010 Mar 20;28(9):1458-66. doi: 10.1200/JCO.2009.24.9557. Epub 2010 Feb 16.

Courneya KS, McKenzie DC, Mackey JR, Gelmon K, Friedenreich CM, Yasui Y, Reid RD, Vallerand JR, Adams SC, Proulx C, Dolan LB, Wooding E, Segal RJ. Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy. Br J Cancer. 2014 Oct 28;111(9):1718-25. doi: 10.1038/bjc.2014.466. Epub 2014 Aug 21.

Edvardsen E, Hem E, Anderssen SA. End criteria for reaching maximal oxygen uptake must be strict and adjusted to sex and age: a cross-sectional study. PLoS One. 2014 Jan 14;9(1):e85276. doi: 10.1371/journal.pone.0085276. eCollection 2014.

Peel AB, Thomas SM, Dittus K, Jones LW, Lakoski SG. Cardiorespiratory fitness in breast cancer patients: a call for normative values. J Am Heart Assoc. 2014 Jan 13;3(1):e000432. doi: 10.1161/JAHA.113.000432.

• Responsible Party: Inger Thune, Professor, Oslo University Hospital
• ClinicalTrials.gov Identifier: NCT02240836
• Other Study ID Numbers: 2014/945-1
• First Posted: September 16, 2014
• Last Update Posted: April 26, 2021
• Last Verified: April 2021

Additional relevant MeSH terms:

Breast Neoplasms; Carcinoma in Situ; Carcinoma, Lobular; Breast Carcinoma In Situ; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary