Exercise Programs in Healthy Young Women at Increased Risk of Developing Breast Cancer

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.