Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis
Open accessAbstract
Evidence is strong that a reduction in risk for breast cancer is associated with moderate to vigorous physical activity (PA); however, there is limited understanding of the role of type, intensity, duration, and frequency of PA and their mechanisms in accounting for this health benefit. The objective of this review is to stimulate investigations of candidate mechanisms that may account for the effects of the intensity and duration of aerobic PA on breast cancer risk and tumor burden. Three hypotheses are considered: 1) the mTOR network hypothesis: PA inhibits carcinogenesis by suppressing the activation of the mTOR signaling network in mammary carcinomas; 2) the hormesis hypothesis: the carcinogenic response to PA is nonlinear and accounted for by a physiological cellular stress response; and 3) the metabolic reprogramming hypothesis: PA limits the amount of glucose and glutamine available to mammary carcinomas thereby inducing apoptosis because tumor‐associated metabolic programming is reversed. To link these hypotheses to systemic effects of PA, it is recommended that consideration be given to determining: 1) what contracting muscle releases into circulation or removes from circulation that would directly modulate the carcinogenic process in epithelial cells; 2) whether the effects of muscle contraction on epithelial cell carcinogenesis are exerted in an endocrine, paracrine, autocrine, or intracrine manner; and 3) if the effects of muscle contraction on malignant cells differ from effects on normal or premalignant cells that do not manifest the hallmarks of malignancy. © 2009 IUBMB IUBMB Life 61(9): 895–901, 2009
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Impact of exercise on cancer: mechanistic perspectives and new insights
Ye, F., Feng, X., Wan, R., Luo, Z., Qu, L., & Wang, Q. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1474770 · Cited by 51 · see citing works
Goh, J., & Ladiges, W. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2014.06.004 · Cited by 50 · see citing works
Kou, X., Chen, D., & Chen, N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071591 · Cited by 50 · see citing works
The therapeutic potential of exercise to treat cachexia
Lira, F. S., Antunes, B. M., Seelaender, M. C. L., & Neto, J. C. R. (2015) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000170 · Cited by 48 · see citing works
Amani-Shalamzari, S., Agha-Alinejad, H., Alizadeh, S., Shahbazi, S., Khatib, Z. K., Kazemi, A., Saei, M. A., & Minayi, N. (2014) · PubMed Central · Cited by 47 · see citing works
Cancer, Physical Activity, and Exercise
Brown, J. C., Winters‐Stone, K. M., Lee, A. C., & Schmitz, K. H. (2012) · Comprehensive physiology · doi:10.1002/j.2040-4603.2012.tb00476.x · Cited by 46 · see citing works
“In a review by Thompson et al. (162) numerous candidate pathways have been identified to associate with varying doses of physical activity in animal models of mammary carcinogenesis (Fig.”
Fournier, A., Santos, G. D., Guillas, G., Bertsch, J., Duclos, M., Boutron‐Ruault, M., Clavel‐Chapelon, F., & Mesrine, S. (2014) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-14-0150 · Cited by 45 · see citing works
Zhu, Z., Jiang, W., Zacher, J. H., Neil, E. S., McGinley, J. N., & Thompson, H. J. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0454 · Cited by 45 · see citing works
“Mechanistic inquiries of the relationship between energetics and cancer risk canbedivided into the investigationof host systemic factors and cell autonomous processes, and undoubtedly they are related and both are important to the full understanding of how various interventions impact breast cancer risk (15, 16).”
Self-citationOrange, S. T., Jordan, A., & Saxton, J. (2020) · Physiological Reports · doi:10.14814/phy2.14635 · Cited by 35 · see citing works
“For instance, murine studies show that aerobic exercise regulates the Protein Kinase B/mammalian target of rapamycin (AKT/mTOR) signaling pathway (Thompson et al., 2009) which is a key cell growth regulator and is hyperactivated in many cancer types (Porta et al.”
The Influence of Exercise on Cancer Risk, the Tumor Microenvironment and the Treatment of Cancer
He, A., Pu, Y., Jia, C., Wu, M., He, H., & Xia, Y. (2024) · Sports Medicine · doi:10.1007/s40279-024-02031-2 · Cited by 29 · see citing works
“Exercise is involved in the regulation of metabolism-related pathways, including the mammalian target of rapamycin (mTOR), which may represent a molecular target for cancer suppression mediated by exercise training [157].”
Steiner, J. L., DAVIS, J. M., McClellan, J. L., Enos, R. T., & Murphy, E. A. (2013) · International Journal of Oncology · doi:10.3892/ijo.2013.1827 · Cited by 25 · see citing works
Lee, M., Lee, Y., Jang, D., & Shin, A. (2021) · Cancers · doi:10.3390/cancers13194804 · Cited by 25 · see citing works
Thompson, H. J., Wolfe, P., McTiernan, A., Jiang, W., & Zhu, Z. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0078 · Cited by 25 · see citing works
Self-citationFigueira, A. C., Cortinhas, A., Soares, J., Leitão, J. C., Ferreira, R. M., & Duarte, J. A. (2018) · International Journal of Sports Medicine · doi:10.1055/s-0044-101149 · Cited by 23 · see citing works
“…0.862 – 0.685 – 0.384 – 0.752 – 0.946 – 0.474 Jiang, Zhu and Thompson, 2009 a Jiang, Zhu and Thompson, 2009 b Jiang, Zhu and Thompson, 2009 c Jiang, Zhu and Thompson, 2013 Jiang, Zhu and Thompson, 2013 Zhu, Jiang, Thompson et al, 2009 Zhu, Jiang, Thompson et al, 2009 Zhu, Jiang, Thompson et…”
BackgroundResultInfluentialHara, M., Nishida, Y., Shimanoe, C., Otsuka, Y., Nanri, H., Yasukata, J., Miyoshi, N., Yamada, Y., Horita, M., Kawai, K., et al. (2016) · Cancer Science · doi:10.1111/cas.13070 · Cited by 19 · see citing works
Jiang, W., Zhu, Z., & Thompson, H. J. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs350 · Cited by 18 · see citing works
Self-citationInherent aerobic capacity-dependent differences in breast carcinogenesis
Thompson, H. J., Jones, L. W., Koch, L. G., Britton, S. L., Neil, E. S., & McGinley, J. N. (2017) · Carcinogenesis · doi:10.1093/carcin/bgx066 · Cited by 15 · see citing works
Self-citationExercise-induced extracellular vesicles in reprogramming energy metabolism in cancer
Puurand, M., Llorente, A., Linē, A., & Käämbre, T. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2024.1480074 · Cited by 13 · see citing works
Exercise May Affect Metabolism in Cancer-Related Cognitive Impairment
Shahid, M., & Kim, J. (2020) · Metabolites · doi:10.3390/metabo10090377 · Cited by 12 · see citing works
The interplay of exercise and green tea: a new road in cancer therapy
Liu, B., Tian, H., & Momeni, M. R. (2025) · Cancer Cell International · doi:10.1186/s12935-024-03632-7 · Cited by 12 · see citing works
Metabolic Rewiring During Metastasis: The Interplay Between the Environment and the Host
Vandekeere, A., Kharraz, S. E., Altea‐Manzano, P., & Fendt, S. (2024) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062822-122840 · Cited by 9 · see citing works
IGF-1 Mediates Exercise-Induced Phospholipid Alteration in the Murine Skin Tissues
Jiang, Y. (2012) · Journal of Nutrition & Food Sciences · doi:10.4172/2155-9600.s2-003 · Cited by 9 · see citing works
“Several proposed hypotheses include DNA repair, apoptosis regulation, oncogene inhibition and hormone alteration [8].”
BackgroundKruk, J. (2012) · Współczesna Onkologia · doi:10.5114/wo.2012.32493 · Cited by 8 · see citing works
Yang, G., Yang, W., & Kiarasi, F. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.70758 · Cited by 7 · see citing works
Decoding the Inter-Relationship between Sleep Disorders and Alzheimer’s Disease Pathogenesis
Mueed, Z., Rai, P. K., Kamal, M. A., & Poddar, N. K. (2020) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527319666200903161249 · Cited by 6 · see citing works
Isolation and Characterization of Muscle Fatigue Substance with Anti-Tumor Activities
Muñoz, R. M., Han, H., Tegeler, T. J., Pétritis, K., Hoff, D. D. V., & Hoffman, S. A. (2013) · Journal of Cancer · doi:10.7150/jca.5418 · Cited by 6 · see citing works
“Our current results are also consistent with Thompson’s recent report showing apoptosis in breast cancer cells injected with extracts isolated from stimulated muscles (14).”
ResultInfluentialAdvancements in Understanding and Preventing Obesity-Related Colon Cancer
Shieh, C., Thompson, H. J., McLaughlin, E. M., Chiang, C., & Hussan, H. (2024) · The Cancer Journal · doi:10.1097/ppo.0000000000000744 · Cited by 5 · see citing works
Self-citationDasgupta, A., & Klein, K. L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405872-9.00008-2 · Cited by 5 · see citing works
Encabo, P. G., Valadés, D., de Cos, A. I., García‐Honduvilla, N., & Pérez‐López, A. (2019) · Science & Sports · doi:10.1016/j.scispo.2018.09.012 · Cited by 3 · see citing works
Houben, L. H. P., Tuytten, T. R. A. H., Holwerda, A. M., Wisanto, E., Senden, J. M., Wodzig, W. K. W. H., Damink, S. W. M. O., Beelen, M., Beijer, S., van Renterghem, K., et al. (2023) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003349 · Cited by 2 · see citing works
“Evidence suggests that higher physical activity levels downregulate translational signaling involved in the regulation of tumor protein synthesis, with enhanced AMPK activity and suppressed mTOR activity appearing to play central roles (14 – 16).”
BackgroundLutsiv, T., McGinley, J. N., Neil, E. S., & Thompson, H. J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061506 · Cited by 2 · see citing works
Self-citationBarbieri, E., Falcieri, E., Santi, M. D., Natalucci, V., Vallorani, L., Agostini, D., Annibalini, G., Stefani, L., Szychlinska, M. A., & Musumeci, G. (2018) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk3020023 · Cited by 2 · see citing works
Relations entre activité physique, équilibre pondéral et cancer du sein
Maître, C. (2013) · Annales d Endocrinologie · doi:10.1016/j.ando.2013.02.006 · Cited by 1 · see citing works
Ahmadian, M., Azizbeigi, K., Delfan, M., & Atashak, S. (2019) · Medical Journal of Tabriz University of Medical Sciences and Health Services · doi:10.34172/mj.2019.001 · Cited by 1 · see citing works
Masoudzade, G. (2019) · Iranian Journal of Breast Disease · doi:10.30699/acadpub.ijbd.11.04.17
Mohamed, M., Shabanah, M., Samir, S. M., Gad, G. E. M., & Elserougy, H. G. (2020) · Bulletin of Egyptian Society for Physiological Sciences · doi:10.21608/besps.2020.29480.1058
“Irisin levels increase during exercise training (40, 41).”
BackgroundIlozumba, M. N., Yaghjyan, L., Datta, S., Zhao, J., Gong, Z., Hong, C., Lunetta, K. L., Zirpoli, G., Bandera, E. V., Palmer, J. R., et al. (2023) · Breast Cancer Research and Treatment · doi:10.1007/s10549-023-06902-6
“In animal models, physical activity is associated with decreased signaling of mTOR and its downstream targets in mammary cancer [35], and the influence may be independent of weight reduction [40].”
BackgroundZhu, Z., Jiang, W., Zacher, J. H., Neil, E. S., McGinley, J. N., & Thompson, H. J. (2023) · doi:10.1158/1940-6207.c.6544233
Self-citationExercise training in prostate cancer patients on androgen deprivation therapy
Houben, L. H. P. (2024) · doi:10.26481/dis.20240111lh
- Authors
- Thompson, H. J., Jiang, W., & Zhu, Z.
- Affiliations
- Colorado State University (US)
- Corresponding author
- Thompson, Henry J.
- Venue
- IUBMB Life
- Publisher
- Wiley
- Published
- 2009-07-08
- Volume
- 61
- Issue
- 9
- Pages
- 895-901
- ISSN
- 1521-6543 (ISSN-L)
- 1521-6551
- PMC
- PMC4346290
- OpenAlex
- W2039413115
- Cited by
- 59
- References
- 57
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 9
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- IUBMB Life (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA100693, CA100693, U54CA116847)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- physical activity, breast cancer, mammary carcinogenesis, mTOR signaling, hormesis, metabolic reprogramming, aerobic exercise, exercise intensity and duration, muscle contraction, tumor burden, apoptosis, paracrine signaling, cancer prevention
- MeSH terms
- Breast Neoplasms, Female, Humans, Exercise
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