Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

BACKGROUND: Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. METHODS: A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. RESULTS: We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). CONCLUSIONS: In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. IMPACT: Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR.

Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial.

UNLABELLED: Medical and surgical interventions for elevated breast cancer risk (e.g., BRCA1/2 mutation, family history) focus on reducing estrogen exposure. Women at elevated risk may be interested in less aggressive approaches to risk reduction. For example, exercise might reduce estrogen, yet has fewer serious side effects and less negative impact than surgery or hormonal medications. Randomized controlled trial. Increased risk defined by risk prediction models or BRCA mutation status. Eligibility: Age 18-50, eumenorrheic, non-smokers, and body mass index (BMI) between 21 and 50 kg/m(2). 139 were randomized. Treadmill exercise: 150 or 300 min/week, five menstrual cycles. Control group maintained exercise <75 min/week. PRIMARY OUTCOME: Area under curve (AUC) for urinary estrogen. Secondary measures: urinary progesterone, quantitative digitized breast dynamic contrast-enhanced magnetic resonance imaging background parenchymal enhancement. Mean age 34 years, mean BMI 26.8 kg/m(2). A linear dose-response relationship was observed such that every 100 min of exercise is associated with 3.6 % lower follicular phase estrogen AUC (linear trend test, p = 0.03). No changes in luteal phase estrogen or progesterone levels. There was also a dose-response effect noted: for every 100 min of exercise, there was a 9.7 % decrease in background parenchymal enhancement as measured by imaging (linear trend test, p = 0.009). Linear dose-response effect observed to reduce follicular phase estrogen exposure measured via urine and hormone sensitive breast tissue as measured by imaging. Future research should explore maintenance of effects and extent to which findings are repeatable in lower risk women. Given the high benefit to risk ratio, clinicians can inform young women at increased risk that exercise may blunt estrogen exposure while considering whether to try other preventive therapies.

Women In Steady Exercise Research (WISER) Sister: study design and methods.

PURPOSE: Women at elevated risk for breast cancer are motivated to reduce their risk. Current approaches rely primarily on hormonal intervention. A preventive exercise intervention might address the same hormonal issues, yet have fewer serious side effects and less negative impact on quality of life as compared to prophylactic mastectomy. WISER Sister was a randomized controlled trial which examined effects of two doses of exercise training on endogenous sex hormone exposure, hormonally active breast tissue, and other breast cancer risk factors. METHODS: Subjects for this single site trial were recruited from across the U.S., in collaboration with organizations that serve women at elevated risk, via emails, flyers, and letters. Eligibility criteria included age ≥ 18, eumenorrheic, and at elevated risk for breast cancer (e.g. BRCA1 or BRCA2 mutation and/or ≥ 18% lifetime risk according to prediction models). A 1:1:1 randomization scheme was used to allocate participants into: control, low dose (150 min/week), or high dose (300 min/week) home based treadmill exercise. Participants provided first morning urine samples daily for two menstrual cycles at study beginning and end for calculation of endogenous hormone exposure. In addition, women completed breast dynamic contrast enhanced magnetic resonance imaging, a fasting blood draw, a treadmill exercise test, and surveys at baseline and follow-up. DISCUSSION: WISER Sister randomized 139 women, 122 of whom completed the study. The overall drop-out rate was 12%. Findings will be useful in understanding the potential for exercise to assist with reducing risk for breast cancer among women at elevated risk.

Patterns of weight change in black Americans: pooled analysis from three behavioral weight loss trials.

OBJECTIVE: Differentiating trajectories of weight change and identifying associated baseline predictors can provide insights for improving behavioral obesity treatment outcomes. METHODS: Secondary, observational analyses using growth mixture models were conducted in pooled data for 604 black American, primarily female adults in three completed clinical trials. Covariates of identified patterns were evaluated. RESULTS: The best fitting model identified three patterns over 2 years: 1) mean weight loss of approximately 2 kg (n = 519); 2) mean weight loss of approximately 3 kg at 1 year, followed by ∼4 kg regain (n = 61); and 3) mean weight loss of ∼20 kg at 1 year followed by ∼4 kg regain (n = 24, with 23 from one study). In final multivariate analyses, higher BMI predicted having pattern 2 (OR [95% CI]) 1.10 [1.03, 1.17]) or 3 (OR [95% CI] 1.42 [1.25, 1.63]), and higher dietary fat score was predictive of a lower odds of having patterns 2 (OR [95% CI] 0.37[0.15, 0.94]) or 3 (OR [95% CI] 0.23 [0.07, 0.79]). CONCLUSIONS: Findings were consistent with moderate, clinically non-significant weight loss as the predominant pattern across all studies. Results underscore the need to develop novel and more carefully targeted and tailored approaches to facilitating weight loss in black American adults.