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

Authors
  • Demark-Wahnefried, Wendy1, 2
  • Rogers, Laura Q2, 3
  • Gibson, Justin T1
  • Harada, Shuko2, 4
  • Frugé, Andrew D5
  • Oster, Robert A1, 3
  • Grizzle, William E2, 4
  • Norian, Lyse A1, 2
  • Yang, Eddy S2, 6
  • Della Manna, Deborah6
  • Jones, Lee W7
  • Azrad, Maria8
  • Krontiras, Helen2, 9
  • 1 Department of Nutrition Sciences, University of Alabama at Birmingham (UAB) 1675 University Blvd, Birmingham, AL.
  • 2 O'Neal Comprehensive Cancer Center at UAB, Birmingham, AL.
  • 3 Division of Preventive Medicine, Birmingham, AL.
  • 4 Department of Pathology, Birmingham, AL.
  • 5 Auburn University, Auburn, AL.
  • 6 Department of Radiation Oncology, UAB, Birmingham, AL.
  • 7 Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY.
  • 8 Department of Human Nutrition, Tuscaloosa, AL.
  • 9 Department of Surgery, UAB, Birmingham, AL.
Type
Published Article
Journal
International Journal of Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
May 15, 2020
Volume
146
Issue
10
Pages
2784–2796
Identifiers
DOI: 10.1002/ijc.32637
PMID: 31442303
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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