Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics Journal Article


Authors: Demark-Wahnefried, W.; Rogers, L. Q.; Gibson, J. T.; Harada, S.; Frugé, A. D.; Oster, R. A.; Grizzle, W. E.; Norian, L. A.; Yang, E. S.; Della Manna, D.; Jones, L. W.; Azrad, M.; Krontiras, H.
Article Title: Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics
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 CD56dimNK 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. © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
Keywords: clinical trial; breast cancer; exercise; diet; ki67
Journal Title: International Journal of Cancer
Volume: 146
Issue: 10
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 2020-05-15
Start Page: 2784
End Page: 2796
Language: English
DOI: 10.1002/ijc.32637
PUBMED: 31442303
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Lee Winston Jones
    129 Jones