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

Wendy Demark-Wahnefried, Laura Q. Rogers, Justin T. Gibson, Shuko Harada, Andrew D. Frugé, Robert A. Oster, William E. Grizzle, Lyse A. Norian, Eddy S. Yang, Deborah Della Manna, Lee W. Jones, Maria Azrad, Helen Krontiras

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish
Pages (from-to)2784-2796
Number of pages13
JournalInternational Journal of Cancer
Issue number10
StatePublished - May 15 2020

Bibliographical note

Funding Information:
We thank the efforts of Drs Kimberly Keene, Catherine Parker, Jennifer De Los Santos, Drexell Boggs, Marshall Urist, Carla Falkson, Andres Forero, Kirby Bland, Chris Vaklavas, Erica Stringer-Reasor, Yuko Tsuruta and Markus Bredel. Moreover, we are grateful for the assistance from Alma del Grosso, RN, Kathleen Romundstad, RN, Sara Mansfield, MS, ACSM Certified Exercise Trainer (CET), Alexandra Yates, MS, ACSM CET, Britney Blackstock, Heather Hunter, MS, Madeline Morgan and Lora Roberson. We also are appreciative of the UAB nanoString Shared Resource. Most all, we acknowledge the efforts of our study participants without whom this research would not be possible.

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


  • Ki67
  • breast cancer
  • clinical trial
  • diet
  • exercise

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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