Exercise Programs in Healthy Young Women at Increased Risk of Developing Breast Cancer
Condition: Breast Cancer; Healthy, no Evidence of Disease
MeSH terms: Breast Neoplasms
Study type: Interventional

Summary: 
      RATIONALE: Exercise may change the risk of developing breast cancer. It is not yet known
      whether low-intensity exercise or high-intensity exercise is more effective in lowering the
      risk of breast cancer.

      PURPOSE: This randomized clinical trial is studying how well exercise programs work in
      healthy young women at increased risk of developing breast cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To conduct a dose response study of low- or high-dose exercise over 5 menstrual cycles,
           with no concomitant dietary changes producing a caloric deficit, in healthy younger
           women with ≥ 18% lifetime risk for developing breast cancer.

        -  To determine the effects of this exercise regimen on variables known to be associated
           with breast mitotic activity in these participants.

      Secondary

        -  To assess changes in other physiologic parameters associated with breast mitotic
           activity (i.e., urinary progesterone [pregnanediol-glucuronide, PdG] from daily first
           morning urine samples; follicular phase circulating [serum] levels of estradiol,
           progesterone, testosterone, and prolactin; follicular phase breast density
           [fibroglandular tissue volume] from magnetic resonance imaging; estrogen metabolites
           [estrone, estradiol, estriol, 2-OHE_1, 2-OHE_2, 4-OHE_1, 4-OHE_2, 16-OHE_1 and ratios];
           adipokines [i.e., adiponectin and Leptin]; and body composition [i.e., % body fat, lean
           mass, fat mass, total mass]) in these participants.

        -  To assess the extent to which changes in body composition and/or body mass mediate
           observed changes in these participants.

        -  To quantify the relationship between estrogen and progesterone from daily urinary
           measurements with observed menstrual cycle alterations such as follicular and luteal
           phase length changes, and ovulatory status in these participants.

        -  To compare levels and exercise-induced changes in urinary estrogens, estrogen
           metabolites, circulating hormones, adipokines, and body size across two groups of women
           who differ as to breast cancer risk in an exploratory manner.

      OUTLINE: Patients are stratified according to body mass index (21-29.9 vs 30-50) and
      gynecologic age (< 10 vs ≥ 10 years since start of menstruation). Participants are randomized
      to 1 of 3 intervention arms.

        -  Arm I (control): Participants are placed on a waiting list to receive the exercise
           intervention at completion of the study.

        -  Arm II: Participants undergo a low-intensity exercise program comprising 150 minutes of
           exercise per week for 20 weeks. They are given a treadmill at the beginning of the study
           and offered ongoing support from a certified exercise professional. Participants may
           exercise at home on the provided treadmill or at a gym of their choosing. Participants
           must maintain weekly contact with the exercise professional for the duration of the
           study, either by phone for brief phone counseling or at a weekly group exercise session
           at a participating YMCA. The exercise professional visits the participant's home for the
           first exercise session of each of the first 5 weeks to help individualize the intensity
           and duration of the exercise session and to instruct participants on the use of the
           exercise logs and on injury prevention.

      Exercise intensity is measured by a Polar Heart Rate monitor worn by the participant to
      record heart rate response during exercise. Every two weeks, the exercise professional
      reviews downloadable heart-rate data from the monitor during the home or group exercise
      session, to objectively measure exercise adherence and provide guidance and emotional support
      to the participant.

        -  Arm III: Participants undergo a high-intensity exercise program that begins with 150
           minutes of exercise per week and then gradually builds to 300 minutes per week over 10
           weeks. Participants continue to exercise at the higher level until the end of the
           20-week intervention period. Participants also undergo exercise and heart rate
           monitoring and brief phone counseling as in arm II.

      Blood and urine samples are obtained from participants periodically before and/or during
      study to evaluate factors associated with breast mitotic activity and linked to breast cancer
      risk: urinary conjugates (i.e., E1G and PdG) by enzyme immunoassays; urinary estrogen
      metabolites by gas chromatography/mass spectrometry; circulating hormones (i.e., estradiol,
      progesterone, testosterone, and prolactin) by radioimmunoassay; and adipokines (i.e.,
      adiponectin and leptin) by sandwich ELISA. Participants also undergo physical assessments,
      including periodic measures of body composition by DEXA, follicular phase breast density
      (fibroglandular tissue volume) by MRI, and height and weight. Aerobic fitness and physical
      activity levels are also assessed.

      Participants complete surveys and questionnaires periodically during study to obtain
      information on demographics, health history, medication use, eating disorders, dietary
      intake, and menstrual history.
    

Intervention name(s): exercise intervention; counseling intervention; gas chromatography; immunoenzyme technique; immunologic technique; laboratory biomarker analysis; mass spectrometry; physiologic testing; questionnaire administration; survey administration; dual x-ray absorptometry; magnetic resonance imaging; study of high risk factors
Intervention type(s): Behavioral; Other; Other; Other; Other; Other; Other; Other; Other; Other; Procedure; Procedure; Procedure
Intervention model: Single Group Assignment
Masking: Single
Primary purpose: Other
Keywords: breast cancer; healthy, no evidence of disease