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Peer-reviewedCC BY 4.0Metabolites

Exploratory Plasma Metabolomic Analysis of Aerobic Exercise-Associated Responses During Anthracycline-Based Chemotherapy in Patients with Breast Cancer: A Randomized Controlled Trial

  • Hongmei Li1,2
  • Jing Zuo2
  • Jingzhe Xiao3
  • Die Sang4
  • Yimin Zhang2,5
  • Lijing Gong5,6,7
7 affiliations
  1. 1School of Physical Education, South-Central Minzu University, Wuhan 430074, China
  2. 2School of Sport Science, Beijing Sport University, Beijing 100084, China
  3. 3China Ice Sport College, Beijing Sport University, Beijing 100084, China
  4. 4Department of Breast Medicine, Sanhuan Cancer Hospital, Beijing 100021, China
  5. 5Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China
  6. 6China Institute of Sport and Health Science, Beijing Sport University, Beijing 100084, China
  7. 7Key Laboratory for Performance Training & Recovery of General Administration of Sport, Beijing 100084, China
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Abstract

Background/Objectives: Anthracycline-based chemotherapy is associated with systemic toxicities in patients with breast cancer. Aerobic exercise may help mitigate treatment-related effects, but its associated metabolic responses during chemotherapy remain poorly understood. This study assessed biochemical and circulating metabolomic responses to aerobic exercise during anthracycline-based chemotherapy. Methods: This exploratory secondary analysis included 40 participants from a randomized controlled trial (trained n = 21; control, n = 19). Participants in the trained group completed a 12-week aerobic exercise intervention during chemotherapy. Biochemical markers and untargeted plasma LC–MS metabolomic profiles were assessed before and after intervention. Exploratory metabolic candidates were evaluated using linear mixed-effects models with Benjamini–Hochberg correction. Results: Significant Group × Time interactions were observed for 10 of 12 physiological and biochemical markers after BH-FDR correction in the primary analysis. However, baseline-adjusted ANCOVA sensitivity analyses showed that only IL-6 retained statistical significance after BH-FDR correction (adjusted between-group difference: −15.58 pg/mL, 95% CI: −20.72 to −10.45; FDR < 0.001). Despite limited global metabolomic separation, sequential screening identified 26 candidate features, seven of which showed significant Group × Time interactions after correction across candidates. Five had putative annotations, including lysophosphatidylcholine (LPC) 14:1, lysophosphatidylethanolamine (LPE) 17:1, cis-7-hexadecenoic acid, L-ascorbate, and vitamin E acetate. In a full-feature sensitivity analysis, only Com_3317_pos remained significant after BH-FDR correction across all 1150 metabolic features (FDR = 0.0228). Conclusions: Aerobic exercise during anthracycline-based chemotherapy was associated with changes in circulating biochemical markers, although these findings were less robust after baseline adjustment. Untargeted metabolomics identified exploratory exercise-associated metabolic features, particularly those putatively related to lipid metabolism, but most did not remain significant after full-feature multiple-testing correction. Further validation is warranted.

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Cite

BibTeXRIS
BibTeX
@article{li2026exploratory,
  title = {{Exploratory Plasma Metabolomic Analysis of Aerobic Exercise-Associated Responses During Anthracycline-Based Chemotherapy in Patients with Breast Cancer: A Randomized Controlled Trial}},
  author = {Hongmei Li and Jing Zuo and Jingzhe Xiao and Die Sang and Yimin Zhang and Lijing Gong},
  journal = {Metabolites},
  year = {2026},
  month = nov,
  doi = {10.3390/metabo16110869},
  url = {https://www.mdpi.com/2218-1989/16/11/869},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Exploratory Plasma Metabolomic Analysis of Aerobic Exercise-Associated Responses During Anthracycline-Based Chemotherapy in Patients with Breast Cancer: A Randomized Controlled Trial
AU  - Hongmei Li
AU  - Jing Zuo
AU  - Jingzhe Xiao
AU  - Die Sang
AU  - Yimin Zhang
AU  - Lijing Gong
PY  - 2026
DA  - 2026/11/09
JO  - Metabolites
DO  - 10.3390/metabo16110869
UR  - https://www.mdpi.com/2218-1989/16/11/869
AB  - Background/Objectives: Anthracycline-based chemotherapy is associated with systemic toxicities in patients with breast cancer. Aerobic exercise may help mitigate treatment-related effects, but its associated metabolic responses during chemotherapy remain poorly understood. This study assessed biochemical and circulating metabolomic responses to aerobic exercise during anthracycline-based chemotherapy. Methods: This exploratory secondary analysis included 40 participants from a randomized controlled trial (trained n = 21; control, n = 19). Participants in the trained group completed a 12-week aerobic exercise intervention during chemotherapy. Biochemical markers and untargeted plasma LC–MS metabolomic profiles were assessed before and after intervention. Exploratory metabolic candidates were evaluated using linear mixed-effects models with Benjamini–Hochberg correction. Results: Significant Group × Time interactions were observed for 10 of 12 physiological and biochemical markers after BH-FDR correction in the primary analysis. However, baseline-adjusted ANCOVA sensitivity analyses showed that only IL-6 retained statistical significance after BH-FDR correction (adjusted between-group difference: −15.58 pg/mL, 95% CI: −20.72 to −10.45; FDR < 0.001). Despite limited global metabolomic separation, sequential screening identified 26 candidate features, seven of which showed significant Group × Time interactions after correction across candidates. Five had putative annotations, including lysophosphatidylcholine (LPC) 14:1, lysophosphatidylethanolamine (LPE) 17:1, cis-7-hexadecenoic acid, L-ascorbate, and vitamin E acetate. In a full-feature sensitivity analysis, only Com_3317_pos remained significant after BH-FDR correction across all 1150 metabolic features (FDR = 0.0228). Conclusions: Aerobic exercise during anthracycline-based chemotherapy was associated with changes in circulating biochemical markers, although these findings were less robust after baseline adjustment. Untargeted metabolomics identified exploratory exercise-associated metabolic features, particularly those putatively related to lipid metabolism, but most did not remain significant after full-feature multiple-testing correction. Further validation is warranted.
SN  - 2218-1989
ER  -