Effect of a Low-Calorie Diet and/or Exercise Program on Risk Factors for Developing Breast Cancer in Overweight or Obese Postmenopausal Women
Effect of a Low-Calorie Diet and/or Exercise Program on Risk Factors for Developing Breast Cancer in Overweight or Obese Postmenopausal Women
RATIONALE: A low-calorie diet and/or exercise program may help lower an overweight or obese
 postmenopausal woman's risk of developing breast cancer. It is not yet known whether a
 low-calorie diet and/or exercise program are more effective than no diet or exercise program
 in lowering an overweight or obese postmenopausal woman's risk of developing breast cancer.

 PURPOSE: This randomized clinical trial is studying the effect of a low-calorie diet and/or
 exercise program on risk factors for developing breast cancer compared with no diet or
 exercise program in overweight or obese postmenopausal women.
OBJECTIVES:

 Primary

 -  Compare the effects of a 1-year exercise intervention, reduced-calorie diet
 intervention, or a combined exercise and reduced-calorie diet intervention vs no
 intervention on serum estrone concentrations in overweight or obese postmenopausal
 women.

 Secondary

 -  Compare the effects of these interventions on serum levels of estradiol and free
 estradiol in these participants.

 -  Compare the effects of these interventions on serum levels of testosterone and free
 testosterone in these participants.

 -  Compare the effects of these interventions on serum levels of sex hormone binding
 globulin in these participants.

 -  Compare the effects of these interventions on serum levels of insulin in these
 participants.

 -  Compare the effects of these interventions on serum levels of glucose in these
 participants.

 -  Compare the effects of these interventions on serum levels of c-peptide in these
 participants.

 -  Compare the effects of these interventions on serum levels of insulin-like growth factor
 I (IGF-1) in these participants.

 -  Compare the effects of these interventions on serum levels of insulin-like growth factor
 binding-protein-3 (IGFBP-3) in these participants.

 -  Compare the effects of these interventions on serum levels of c-reactive protein (CRP)
 in these participants.

 -  Compare the effects of these interventions on serum levels of serum amyloid protein A
 (SAA) in these participants.

 -  Compare the effects of these interventions on serum levels of interleukin-6 (IL-6) in
 these participants.

 -  Compare the effects of these interventions on serum levels of adiponectin in these
 participants.

 -  Compare the effects of these interventions on serum levels of leptin in these
 participants.

 -  Compare the effects of these interventions on serum levels of ghrelin in these
 participants.

 -  Compare the effects of these interventions on serum levels of Vitamin D in these
 participants.

 -  Compare the effects of these interventions on mammographic density in these
 participants.

 -  Compare the effects of these interventions on anthropometrics and body composition
 (i.e., weight, body mass index, total and percentage body fat, and waist and hip
 circumferences) in these participants.

 -  Compare the effects of these interventions on quality of life in these participants.

 -  Compare the effects of these interventions on numbers of leukocytes and neutrophiles in
 these participants.

 -  Compare the effects of these interventions on VO2max in these participants.

 OUTLINE: This is a randomized study. Participants are stratified according to body mass index
 (< 30 vs ≥ 30). Participants are randomized to 1 of 4 intervention arms.

 -  Arm I (exercise program): Participants exercise 3 days per week under the supervision of
 a physiologist and 2 days per week independently at home, for a total of 5 exercise
 sessions (at least 45 minutes of moderate-intensity exercise per session) weekly over 12
 months.

 -  Arm II (reduced-calorie diet): Participants meet with a nutritionist individually and in
 small groups. Participants receive general information about diet and behavior
 strategies such as self-monitoring, goal-setting, stimulus-control, problem-solving, and
 relapse-prevention training. Participants learn to set a calorie goal and a fat gram
 goal and how to achieve the goal calorie reduction. Meetings are held weekly during the
 first 6 months of the diet program but taper off over the course of the study.

 -  Arm III (exercise program and reduced-calorie diet): Participants meet with a
 physiologist and a nutritionist, as in arms I and II, and exercise and diet accordingly.

 -  Arm IV (control: delayed diet and exercise): Participants receive study materials on
 healthy diet and exercise at the end of the 12-month study period. In addition,
 participants are offered 2 months of group exercise training with a study physiologist
 and 4 group meetings with a nutritionist to learn about weight loss techniques and
 behavioral principles for achieving weight loss.

 All participants undergo testing at baseline and periodically during study. Participants
 undergo blood collection for evaluation of serum levels of sex and metabolic hormones (e.g.,
 estrone, estradiol, testosterone, free testosterone, and sex hormone binding globulin,
 radioimmunoassay and other immunoassays. Participants also undergo anthropometrics and body
 composition measurements and mammographic density assessment.

 Participants complete questionnaires at baseline and at 6 and 12 months for assessment of
 diet and exercise. Quality of life (QOL) is measured at baseline and at 6 and 12 months using
 the Medical Outcomes Study 36-Item Short Form and the Impact of Weight on QOL questionnaire.
 Information on health habits, medical history, family history of breast cancer, and
 reproductive and menstrual history is also collected.

 FINAL ACCRUAL: A total of 439 participants (118 in the caloric restriction arm, and 117 in
 both the CR+Exercise, and exercise only arm; and 87 in control arm) were accrued for this
 study.
DISEASE CHARACTERISTICS:

 -  At increased risk for developing breast cancer due to any of the following lifestyle
 risk factors:

 -  Lack of physical activity

 -  Excess weight

 -  Obesity

 -  Weight gain over lifetime

 -  Body mass index > 25.0

 -  Physically able to undertake a moderate exercise or calorie reduction program

 -  No history of invasive or in situ breast cancer

 PATIENT CHARACTERISTICS:

 -  Postmenopausal, defined by the absence of periods for the past 12 months

 -  Able to attend study clinic visits and classes, and undergo study measurements

 -  Able to fill out questionnaires and logs in English

 -  No moderate to high alcohol intake (more than 2 drinks per day)

 -  No concurrent smoking

 -  No invasive cancer within the past 10 years except simple basal cell or squamous cell
 carcinoma

 -  No diabetes mellitus

 -  Fasting blood sugar < 126 mg/dL (on 2 occasions)

 -  Hematocrit 32-48%

 -  WBC 3,000-15,000/mm³

 -  Potassium 3.5-5.0 mEq/L

 -  Creatinine ≤ 2.0 mg/dL

 -  No abnormalities on screening physical that contraindicate study participation

 -  No contraindications for treadmill testing or entry into a training program, including
 any of the following:

 -  Myocardial infarction within the past 6 months

 -  Pulmonary edema

 -  Myocarditis

 -  Pericarditis

 -  Unstable angina

 -  Pulmonary embolism or deep vein thrombosis

 -  Uncontrolled hypertension (i.e., blood pressure > 200/100 mm Hg)

 -  Orthostatic hypotension

 -  Moderate-to-severe aortic stenosis

 -  Uncontrolled arrhythmia

 -  Uncontrolled congestive heart failure

 -  Third-degree heart block

 -  Left bundle branch block

 -  Thrombophlebitis

 -  ST depression > 3 mm at rest

 -  History of cardiac arrest or stroke

 -  Normal exercise treadmill testing (ETT)

 -  Negative thallium or echo ETT required for patients with abnormal ETT (defined as
 ≥ 1.5 mm ST depression in > 1 lead within 1-minute recovery OR ≥ 1.1 mm ST
 depression in > 1 lead after 1-minute recovery OR reading of positive test by
 study doctor)

 -  No drug abuse

 -  No significant mental illness

 PRIOR CONCURRENT THERAPY:

 -  More than 6 months since prior and no concurrent menopausal hormone replacement
 therapy of any type, including vaginal route

 -  No concurrent participation in any other organized weight loss or exercise program

 -  No concurrent appetite suppressant medication

 -  No concurrent medications (e.g., weight-loss medications) likely to interfere with
 adherence to interventions or study outcomes