Background and Purpose: Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. There are over 2.5 million breast cancer survivors, 64% of whom are overweight/obese (BMI >25 kg/m2). A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs, and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter adipose tissue inflammation by changing ATM phenotype and cytokine secretion in obese postmenopausal breast cancer survivors.
Experimental Design: Twenty obese postmenopausal breast cancer survivors were recruited from USC and randomized to either the exercise (EX) or control (CON) group. The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Sessions included total-body resistance training consisting of 8 exercises with a rest period of 45 seconds between each set of resistance exercise followed by 30 minutes of moderate-vigorous intensity (65-80% HRmax) aerobic exercise. The CON group was asked to maintain their current activity levels. Superficial subcutaneous abdominal adipose tissue biopsies were performed at baseline and following the 16-week study period. Adipose tissue samples were analyzed using fluorescence-activated cell sorting (FACS) to characterize ATM characterization (M1 vs M2). Portions (~100 mg) of each biopsy were incubated in media overnight to measure cytokine secretion. A 2x2 (group x time) repeated measures ANOVA was used to evaluate changes in adipose tissue and systemic inflammation.
Summary of Results: At baseline, there were no group differences (p>0.05) in age (55.1±5.2 yrs), BMI (34.4±7.5 kg/m2), percent body fat (36.2±4.9%), or ATM M1 (25.4±6.7%) and M2 (4.2±0.9%) levels. EX was associated with a significant decrease in ATM M1 (-18.8±7.3%) and increase in ATM M2 (9.6±1.6%; p<0.01). EX increased adipose tissue secretion of the anti-inflammatory cytokines, adiponectin (14.6±5.2%), IL-12 p40 (2.4±0.8), IL-12 p70 (2.8±1.8%) and decreased secretion of IL-6 (-4.8±2.0%), and TNF-a (-2.0±0.7; p<0.01). The CON group did not experience any changes in ATM characterization and cytokine secretion during the study period (p>0.01).
Conclusions: A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized controlled trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.
Citation Format: Christina M. Dieli-Conwright, Jean Hughes-Parmentier, Kyuwan Lee, Darcy Spicer, Wendy Mack, Fred Sattler, Steven D. Mittelman. Adipose tissue inflammation in breast cancer survivors: Effects of a 16-week aerobic and resistance exercise intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 985. doi:10.1158/1538-7445.AM2017-985