Plain language summary
Obesity directly impacts survival in individuals with breast cancer. Previous studies in animals and at the cellular level have shown that calorie restriction and increased physical activity to achieve a negative energy balance may inhibit cancer progression, however effects in patients are unknown. This randomised control trial aimed to determine the impact of a pre surgery weight loss programme in 32 women with breast cancer on tumour biology and other markers of disease. The results were mixed and showed that proteins which bind to hormones involved in breast cancer were increased, which could decrease severity of disease. However, tumour biology was negatively affected; specific genes involved in breast cancer progression were increased and those involved in tumour suppression were decreased. Although this did result in no net effect on the rate at which new tumours were formed. It was concluded that although the study showed mixed results, ultimately the rate at which new tumours were formed remained unaffected. This trial could be used by healthcare professionals to understand that the role of negative energy intake in breast cancer development is complicated and warrants further research.
Abstract
Obesity adversely impacts overall and cancer-specific survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, feasibility and effects in patients are unknown. A two-arm, single-blinded, randomized controlled weight-loss trial was undertaken presurgery among 32 overweight/obese, Stage 0-II breast cancer patients. The attention control arm (AC) received basic nutritional counseling and upper-body progressive resistance training whereas the weight loss intervention (WLI) arm received identical guidance, plus counseling on caloric restriction and aerobic exercise to promote 0.68-0.92 kg/week weight loss. Anthropometrics, body composition, blood and survey data were collected at baseline and presurgery ∼30 days later. Tumor markers (e.g., Ki67) and gene expression were assessed on biopsy and surgical specimens; sera were analyzed for cytokines, growth and metabolic factors. Significant WLI vs. AC differences were seen in baseline-to-follow-up changes in weight (-3.62 vs. -0.52 kg), %body fat (-1.3 vs. 0%), moderate-to-vigorous physical activity (+224 vs. +115 min/week), caloric density (-0.3 vs. 0 kcal/g), serum leptin (-12.3 vs. -4.0 ng/dl) and upregulation of tumor PI3Kinase signaling and cell cycle-apoptosis related genes (CC-ARG; all p-values <0.05). Cytolytic CD56dim NK cell expression was positively associated with weight loss; CC-ARG increased with physical activity. Increased tumor (nuclear) TNFα and IL-1β, CX3CL1 and CXCL1 gene expression was observed in the WLI. Tumor Ki67 did not differ between arms. Feasibility benchmarks included 80% accrual, 100% retention, no adverse effects and excellent adherence. Short-term weight loss interventions are feasible; however, mixed effects on tumor biology suggest unclear benefit to presurgical caloric restriction, but possible benefits of physical activity.
Methodological quality
Jadad score
:
2
Allocation concealment
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No
