Aerobic Exercise as a Cardioprotective Strategy in Breast Cancer Patients Undergoing Anthracycline-Based Chemotherapy
A Narrative Review
DOI:
https://doi.org/10.12775/QS.2026.68.74425Keywords
breast cancer, anthracyclines, aerobic training, cardiotoxicity, cardioprotection, cardio-oncology, lifestyle, healthAbstract
Background: Advances in breast cancer diagnosis and treatment have significantly extended patient survival, leading to this cancer being increasingly viewed as a chronic disease. However, the use of classic anthracycline-based chemotherapy is associated with a high risk of cardiotoxicity. With extended survival post-therapy, cardiovascular complications emerge as the leading non-oncological cause of mortality among breast cancer survivors
Aim: Summary of the current state of knowledge regarding the role and mechanisms of aerobic training as a cardioprotective strategy in breast cancer patients undergoing anthracycline chemotherapy.
Materials and methods: Analysis of contemporary scientific literature, preclinical studies, and guidelines from international oncology and cardiology societies (e.g., ASCO, ACS, ICOS-CORE).
Results: Anthracyclines damage the myocardium and microcirculation by interacting with topoisomerase IIβ (TOP2B), activating the TGF-β/Smad3 axis, and generating oxidative stress. Aerobic exercise effectively mitigates this cardiotoxicity at the cellular level by strengthening antioxidant defense systems, preserving mitochondrial ultrastructure, promoting biogenesis, and inhibiting apoptotic pathways and myocardial atrophy. Implementing regular exercise during treatment improves therapy tolerance, VO2 peak, and vascular and muscular function.
Conclusions: Regular, structured aerobic training (exercise preconditioning) demonstrates a strong, multifaceted cardioprotective effect. Cardio-oncology rehabilitation programs (CORE) should be an integral component of oncology care and a further research focus.
References
1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3):209–249. https://doi.org/10.3322/caac.21660
2. Yang, M., Yang, Q., Tse, G., Ma, Y., Lyu, Q. Y., Wang, W., Lai, A. Y., Zhang, Y., Wong, C. W. M., & Liu, X. (2026). Effectiveness of self-management interventions in reducing cancer treatment-related cardiotoxicity in breast cancer survivors: A systematic review. Asia-Pacific Journal of Oncology Nursing, 13(1),100931. https://doi.org/10.1016/j.apjon.2026.100931
3. Guan, T., Zhang, H., Yang, J., Lin, W., Wang, K., & Su, M. (2021). Increased Risk of Cardiovascular Death in Breast Cancer Patients Without Chemotherapy or (and) Radiotherapy: A Large Population-Based Study. Frontiers in Oncology, 10:619622. https://doi.org/10.3389/fonc.2020.619622
4. Varghese, S. S., Johnston, W. J., Eekhoudt, C. R., Keats, M. R., Jassal, D. S., & Grandy, S. A. (2021). Exercise to Reduce Anthracycline-Mediated Cardiovascular Complications in Breast Cancer Survivors. Current Oncology, 28(5):4139–4156. https://doi.org/10.3390/curroncol28050351
5. He, J., Wang, S., Liu, H., Duan, C., Zhang, H., Wen, F., & Zhang, C. (2023). Competing risk analysis of cardiovascular death in breast cancer: evidence from the SEER database. Translational Cancer Research, 12(12):3591–3603. https://doi.org/10.21037/tcr-23-1163
6. Migliari, M., Fazzini, L., Campana, N., Deidda, M., Dessì, M., & Cadeddu Dessalvi, C. (2025). Current strategies for prevention of cancer therapy-related cardiotoxicity: pharmacological, non-pharmacological and emerging approaches. Frontiers in Cardiovascular Medicine, 12:1668308. https://doi.org/10.3389/fcvm.2025.1668308
7. Cai, S., Yu, S., Lin, X., Zhou, Q., Zheng, X., Chen, H., Ma, T., Chen, X., Sun, H., & Shi, Y. (2026). Adjuvant pegylated liposomal doxorubicin versus epirubicin sequential paclitaxel in triple-negative breast cancer: comparable efficacy with a distinct safety profile. Frontiers in Immunology, 17:1690888. https://doi.org/10.3389/fimmu.2026.1690888
8. Jensen, B. V. (2006). Cardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer. Seminars in Oncology, 33(3 Suppl 8):S15–S21. https://doi.org/10.1053/j.seminoncol.2006.04.022
9. Cardinale, D., Iacopo, F., & Cipolla, C. M. (2020). Cardiotoxicity of Anthracyclines. Frontiers in Cardiovascular Medicine, 7:26. https://doi.org/10.3389/fcvm.2020.00026
10. Vejpongsa, P., & Yeh, E. T. H. (2014). Prevention of Anthracycline-Induced Cardiotoxicity. Journal of the American College of Cardiology, 64(9):938–945. https://doi.org/10.1016/j.jacc.2014.06.1167
11. Vuong, J. T., Stein-Merlob, A. F., Cheng, R. K., & Yang, E. H. (2022). Novel Therapeutics for Anthracycline Induced Cardiotoxicity. Frontiers in Cardiovascular Medicine, 9:872740. https://doi.org/10.3389/fcvm.2022.872740
12. Wang, Q., Zhang, W., Chen, J., Stenson, K. T., Parsai, S., Parthasarathy, P. B., Wang, L., & Zheng, Z. (2026). Novel Mechanism of and Therapeutic Approach for Anthracycline-Induced Cardiotoxicity. Cancer Research Communications, 6(6):1261–1277. https://doi.org/10.1158/2767-9764.CRC-25-0511
13. Cobb, M. S., Tao, S., Shortt, K., Girgis, M., Hauptman, J., Schriewer, J., Chin, Z., Dorfman, E., Campbell, K., Heruth, D. P., Shohet, R. V., & Dawn, B. (2022). Smad3 promotes adverse cardiovascular remodeling and dysfunction in doxorubicin-treated hearts. American Journal of Physiology-Heart and Circulatory Physiology, 323(6):H1091-H1107. https://doi.org/10.1152/ajpheart.00312.2022
14. Dozic, S., Howden, E. J., Bell, J. R., Mellor, K. M., Delbridge, L. M. D., & Weeks, K. L. (2023). Cellular Mechanisms Mediating Exercise-Induced Protection against Cardiotoxic Anthracycline Cancer Therapy. Cells, 12(9):1312. https://doi.org/10.3390/cells12091312
15. Gaytan, S. L., Lawan, A., Chang, J., Nurunnabi, M., Bajpeyi, S., Boyle, J. B., & Sanchez, C. A. (2023). The beneficial role of exercise in preventing doxorubicin-induced cardiotoxicity. Frontiers in Cardiovascular Medicine,14:1133423 . https://doi.org/10.3389/fphys.2023.1133423
16. Montalvo, R. N., Boeno, F. P., Dowllah, I. M., Moritz, C. E. J., Nguyen, B. L., Doerr, V., & Powers, S. K. (2023). Exercise and Doxorubicin Modify Markers of Iron Overload and Cardiolipin Deficiency in Cardiac Mitochondria. International Journal of Molecular Sciences, 24(9):7689. https://doi.org/10.3390/ijms24097689
17. Christidi, E., & Brunham, L. R. (2021). Regulated cell death pathways in doxorubicin-induced cardiotoxicity. Cell Death & Disease, 12(4):339. https://doi.org/10.1038/s41419-021-03614-x
18. Liu, J., Zheng, H., Tang, M., Ryu, Y. C., & Wang, X. (2008). A therapeutic dose of doxorubicin activates ubiquitin-proteasome system-mediated proteolysis by acting on both the ubiquitination apparatus and proteasome. American Journal of Physiology-Heart and Circulatory Physiology, 295(6):H2541–H2550. https://doi.org/10.1152/ajpheart.01052.2008
19. Ascensão, A., Magalhães, J., Soares, J. M. C., Ferreira, R., Neuparth, M. J., Marques, F., Oliveira, P. J., & Duarte, J. A. (2005). Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. American Journal of Physiology-Heart and Circulatory Physiology, 289(2):H722–H731. https://doi.org/10.1152/ajpheart.01249.2004
20. Kavazis, A. N., Smuder, A. J., & Powers, S. K. (2014). Effects of short-term endurance exercise training on acute doxorubicin-induced FoxO transcription in cardiac and skeletal muscle. Journal of Applied Physiology, 117(3):223–230. https://doi.org/10.1152/japplphysiol.00210.2014
21. Dao, V., Amin, S., Kammaripalle, T., & Manning, K. (2026). Review on cardioprotective strategies in the setting of chemotherapy-induced cardiotoxicity. Cardio-Oncology, 12(1):63. https://doi.org/10.1186/s40959-026-00480-4
22. Uurasmaa, T. M., Bourdin, P., Nammas, W., Latifi, S., Liljenbäck, H., Saraste, A., & Knuuti, J. (2025). Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer. Journal of Translational Medicine, 23(1):89. https://doi.org/10.1186/s12967-025-06108-y
23. Kang, D.-W., Wilson, R. L., Christopher, C. N., Normann, A. J., Barnes, O., Lesansee, J. D., & Jones, L. W. (2022). Exercise Cardio-Oncology: Exercise as a Potential Therapeutic Modality in the Management of Anthracycline-Induced Cardiotoxicity. Frontiers in Cardiovascular Medicine, 8:805735. https://doi.org/10.3389/fcvm.2021.805735
24. Haykowsky, M. J., Weeldreyer, N. R., La Gerche, A., Sarma, S., & Foulkes, S. J. (2026). Impaired peripheral oxygen diffusion is the primary determinant of exercise intolerance in high-risk older breast cancer survivors. American Journal of Physiology-Heart and Circulatory Physiology, 331(1):H318–H326. https://doi.org/10.1152/ajpheart.00324.2026
25. Ligibel, J. A., Bohlke, K., May, A. M., Clinton, S. K., Demark-Wahnefried, W., Gilchrist, S. C., & Wollins, D. S. (2022). Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline. Journal of Clinical Oncology, 40(22):2491–2507. https://doi.org/10.1200/JCO.22.00687
26. Rock, C. L., Thomson, C., Gansler, T., Gapstur, S. M., McCullough, M. L., Patel, A. V., & Bandera, E. V. (2020). American Cancer Society guideline for diet and physical activity for cancer prevention. CA: A Cancer Journal for Clinicians, 70(4):245–271. https://doi.org/10.3322/caac.21591
27. Ghignatti, P. V. C., Marschner, R. A., Ribeiro, R. T., Gayger-Dias, V., Da Silva, V. F., Teixeira, L. V., & Schaan, B. D. (2026). Preventive Aerobic Training Protects Against Doxorubicin-Induced Cardiotoxicity by Preserving Redox Status and Attenuating Cardiac Stress-Related Signaling. Cells, 15(5):408. https://doi.org/10.3390/cells15050408
28. Adams, S. C., Rivera-Theurel, F., Scott, J. M., Nadler, M. B., Foulkes, S., Leong, D., & ICOS-CORE Working Group. (2025). Cardio-oncology rehabilitation and exercise: evidence, priorities, and research standards from the ICOS-CORE working group. European Heart Journal, 46(29):2847–2865. https://doi.org/10.1093/eurheartj/ehaf100
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Copyright (c) 2026 Zuzanna Kruszyńska, Anastasiya Aleshchyk, Michał Adamczak, Marcel Majewski, Bogumił Libura, Martyna Lazar, Łukasz Szkaradowski, Szymon Baranowski, Julia Lewańska, Krzysztof Bogdański
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