One fourth of breast cancer can be attributed to sedentary lifestyles and being overweight or obese. This pilot study was conducted to explore whether a 6-month lifestyle intervention affected body composition and obesity-related biomarkers among women at high risk of breast cancer. Overweight/obese women at high risk of breast cancer were randomized to the control group or to the intervention. The intervention was an individually tailored, cognitive-behavioral therapy program that assists women in identifying strategies to improve their nutrition and physical activity habits with the goal of reduced adiposity. We compared changes in body composition and plasma biomarkers from baseline to 6 months. Body weight, adiposity, leptin, insulin resistance, and C-reactive protein were significantly reduced in the intervention group versus controls. No significant differences were observed in adiponectin, insulin, glucose, or interleukin-6. Our findings suggest that this intervention improves the metabolic and inflammatory profiles of overweight/obese women at risk of breast cancer.

Sedentary lifestyles and obesity are known risk factors for breast cancer. Elevated estrogen levels correlate with obesity and, independently, with increased breast cancer risk. Lifestyle interventions that reduce obesity may mitigate this risk, potentially via estrogen pathways. In a 6-month lifestyle intervention, overweight/obese women with high breast cancer risk were randomized to control ( n = 7) or intervention ( n = 6) and analyzed for sex hormone levels. Serum and urine hormones were evaluated by ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) and sex hormone binding globulin (SHBG) by enzyme-linked immunosorbent assay (ELISA). Serum estrone (E1) and estradiol (E2) were reduced by 12.1% and 50.8%, respectively, at 9 months in the intervention group, which differed from controls ( p = .043 and .020). This contrasted with a 73.3% increase in urine E1 at 6 months in the intervention group ( p = .035). These results suggest that a lifestyle intervention led to a favorable estrogen profile in relation to breast cancer risk.

Background: Breast cancer is the most common non-dermatologic malignancy in women. One-fifth of breast cancers can be attributed to sedentary lifestyles and overweight/obesity. More than two-thirds of U.S. women are overweight or obese. Excess body weight and body fat may affect breast cancer risk through a number of mechanisms, including metabolic pathways (i.e., adipokines, inflammation, and insulin) and estrogen metabolism. To date, limited research has investigated the impact of lifestyle interventions on metabolic changes among women at high risk for breast cancer. The purpose of this pilot study was to test the feasibility of the 6-month exercise and diet intervention and to explore the impact of lifestyle intervention versus control on metabolic changes. Methods: Participants were recruited through the Seattle Cancer Care Alliance. Sixteen women were randomized with half assigned to the control group. Eligible women were 35-65 years of age, had a body mass index (BMI) between 28-40, and were at high risk of breast cancer. Dual-energy X-ray Absorptiometry (DEXA) scans, questionnaire data, blood and urine samples were collected at baseline, 3, 6, and 9- months. The DEEM lifestyle intervention is an individually-tailored intervention that includes motivational enhancement therapy, cognitive and behavioral skills training, and psychological education. Group counseling sessions were conducted weekly for 3 months then tapered over next 3 months. We measured the changes in weight, percent adiposity, central waist/hip circumferences, plasma biomarkers (adiponectin, leptin, C-reactive protein [CRP], Interleukin-6 [IL-6], Homeostatic Model Assessment-Insulin Resistance [HOMA-IR]), and urinary estrogen metabolites (Estrogen DNA Adduct [EDA]). Results: Results showed an average weight loss of 4.1 kg (- 4.6 %) in intervention group versus controls (weight gain 1.4 kg, +1.6 %) at 6 months (p = 0.02). Intervention participants experienced a decrease in percent mean adiposity (-3 %) and waist circumference (-0.2 inches) but no change in hip circumference; controls had increases in all 3 measures (+1.5 %, +0.7 inches, +2.9 inches). These changes were not significantly different. Self-reported physical activity differed between intervention and control participants (6.8 versus.1.4 hrs. /wk., p = 0.01). On average vegetable, fruit, protein intake increased and carbohydrate intake decreased only in intervention group, but not significantly different from controls. Women in the intervention arm reduced plasma CRP (mg/dL) from 0.39 to 0.26 (- 0.13 [34.5 %]) versus from 0.45 to 0.63 (+ 0.18 [39 %]) in controls (p = 0.06); and reduced plasma leptin (ng/ml) from 18.1 to 14.7 (-3.4 [18 %]) versus from 21.8 to 21.9 (+0.1 [0.1 %]) in controls (p = 0.10). Twenty-five percent of the intervention participants went from insulin resistant to non-insulin resistant (HOMA-IR< 2.0), while none of the controls reduced their HOMA-IR. No significant differences were observed in adiponectin, IL-6 and EDA. Conclusion: In this pilot study, the DEEM intervention facilitated weight loss and reduced adiposity. Our findings also suggest that a lifestyle intervention can improve the metabolic health of overweight/obese women at high risk of breast cancer. Future work is needed to confirm this finding in a large-scale study. Citation Format: Claire Jungyoun Han, Larissa Korde, Scott Reding, Kerryn Reding. Impact of a lifestyle intervention on metabolic pathways: Results from the Diet, Exercise, Emotional Processing, and Mindfulness (DEEM) intervention. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A34.