Advertisement

Breast Cancer Research and Treatment

, Volume 168, Issue 1, pp 147–157 | Cite as

Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention

  • Christina M. Dieli-ConwrightEmail author
  • Jean-Hugues Parmentier
  • Nathalie Sami
  • Kyuwan Lee
  • Darcy Spicer
  • Wendy J. Mack
  • Fred Sattler
  • Steven D. Mittelman
Clinical trial

Abstract

Purpose

Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. Obesity stimulates cancer progression through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter ATM phenotype in obese postmenopausal breast cancer survivors.

Methods

Twenty obese postmenopausal breast cancer survivors were randomized to a 16-week aerobic and resistance exercise (EX) intervention or delayed intervention control (CON). The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and superficial subcutaneous abdominal adipose tissue biopsies at baseline and following the 16-week study period.

Results

EX participants experienced significant improvements in body composition, cardiometabolic biomarkers, and systemic inflammation (all p < 0.03 vs. CON). Adipose tissue from EX participants showed a significant decrease in ATM M1 (p < 0.001), an increase in ATM M2 (p < 0.001), increased adipose tissue secretion of anti-inflammatory cytokines such as adiponectin, and decreased secretion of the pro-inflammatory cytokines IL-6 and TNF- α (all p < 0.055).

Conclusions

A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.

Keywords

Adipose tissue Macrophages Obesity Body composition 

Notes

Acknowledgements

We are grateful to the Clinical Investigations Support Office of the Norris Comprehensive Cancer Center for their support of this investigation and the extreme generosity of our study participants. This work was supported by grants K07CA160718 from the National Cancer Institute; and grants UL1TR001855 and UL1TR000130 from the National Center for Advancing Translational Science (NCATS) of the U.S. National Institutes of Health. The content is solely the responsibility of the authors, and does not necessarily represent the official views of the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29CrossRefPubMedGoogle Scholar
  2. 2.
    Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–635CrossRefPubMedGoogle Scholar
  3. 3.
    Iyengar NM, Hudis CA, Dannenberg AJ (2013) Obesity and inflammation: new insights into breast cancer development and progression. American Society of Clinical Oncology educational book/ASCO American Society of Clinical Oncology Meeting:46–51Google Scholar
  4. 4.
    Campbell KL, Makar KW, Kratz M, Foster-Schubert KE, McTiernan A, Ulrich CM (2009) A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk. Cancer Prev Res (Phila) 2(1):37–42CrossRefGoogle Scholar
  5. 5.
    Campbell KL, Foster-Schubert KE, Makar KW, Kratz M, Hagman D, Schur EA et al (2013) Gene expression changes in adipose tissue with diet- and/or exercise-induced weight loss. Cancer Prev Res (Phila) 6(3):217–231CrossRefGoogle Scholar
  6. 6.
    Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35CrossRefPubMedGoogle Scholar
  7. 7.
    Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5(12):953–964CrossRefPubMedGoogle Scholar
  8. 8.
    Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y et al (2009) Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58(11):2574–2582CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cao Y (2010) Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov 9(2):107–115CrossRefPubMedGoogle Scholar
  10. 10.
    Mayi TH, Daoudi M, Derudas B, Gross B, Bories G, Wouters K et al (2012) Human adipose tissue macrophages display activation of cancer-related pathways. J Biol Chem 287(26):21904–21913CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444CrossRefPubMedGoogle Scholar
  12. 12.
    Auerbach P, Nordby P, Bendtsen LQ, Mehlsen JL, Basnet SK, Vestergaard H et al (2013) Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men. Am J Physiol Regul Integr Comp Physiol 305(5):R490–R498CrossRefPubMedGoogle Scholar
  13. 13.
    Ahmadizad S, Ghorbani S, Ghasemikaram M, Bahmanzadeh M (2014) Effects of short-term nonperiodized, linear periodized and daily undulating periodized resistance training on plasma adiponectin, leptin and insulin resistance. Clin Biochem 47(6):417–422CrossRefPubMedGoogle Scholar
  14. 14.
    Kang DW, Lee J, Suh SH, Ligibel J, Courneya KS, Jeon JY (2017) Effects of exercise on insulin, igf axis, adipocytokines, and inflammatory markers in breast cancer survivors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 26(3):355–365CrossRefPubMedGoogle Scholar
  15. 15.
    Meneses-Echavez JF, Correa-Bautista JE, Gonzalez-Jimenez E, Schmidt Rio-Valle J, Elkins MR, Lobelo F et al (2016) The effect of exercise training on mediators of inflammation in breast cancer survivors: a systematic review with meta-analysis. Cancer Epidemiol Biomarkers Prev 25(7):1009–1017CrossRefPubMedGoogle Scholar
  16. 16.
    Ebbeling CB, Ward A, Puleo EM, Widrick J, Rippe JM (1991) Development of a single-stage submaximal treadmill walking test. Med Sci Sports Exerc 23(8):966–973CrossRefPubMedGoogle Scholar
  17. 17.
    Brzycki M (1993) Strength testing: predicting a one-rep max from repetition-to-fatigue. JOHPERD 64:88–90Google Scholar
  18. 18.
    Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL et al (2012) Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62(4):243–274CrossRefPubMedGoogle Scholar
  19. 19.
    Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM et al (2010) American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42(7):1409–1426CrossRefPubMedGoogle Scholar
  20. 20.
    Alderete TL, Sattler FR, Richey JM, Allayee H, Mittelman SD, Sheng X et al (2015) Salsalate treatment improves glycemia without altering adipose tissue in nondiabetic obese hispanics. Obesity (Silver Spring) 23(3):543–551CrossRefGoogle Scholar
  21. 21.
    Oliveira AG, Araujo TG, Carvalho BM, Guadagnini D, Rocha GZ, Bagarolli RA et al (2013) Acute exercise induces a phenotypic switch in adipose tissue macrophage polarization in diet-induced obese rats. Obesity 21(12):2545–2556CrossRefPubMedGoogle Scholar
  22. 22.
    Kawanishi N, Yano H, Yokogawa Y, Suzuki K (2010) Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc Immunol Rev 16:105–118PubMedGoogle Scholar
  23. 23.
    Linden MA, Pincu Y, Martin SA, Woods JA, Baynard T (2014) Moderate exercise training provides modest protection against adipose tissue inflammatory gene expression in response to high-fat feeding. Physiol Rep 2(7):e12071CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Rogers LQ, Fogleman A, Trammell R, Hopkins-Price P, Vicari S, Rao K et al (2013) Effects of a physical activity behavior change intervention on inflammation and related health outcomes in breast cancer survivors: pilot randomized trial. Integr Cancer Ther 12(4):323–335CrossRefPubMedGoogle Scholar
  25. 25.
    Ergun M, Eyigor S, Karaca B, Kisim A, Uslu R (2013) Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients. Eur J Cancer Care (Engl) 22(5):626–637CrossRefGoogle Scholar
  26. 26.
    Hutnick NA, Williams NI, Kraemer WJ, Orsega-Smith E, Dixon RH, Bleznak AD et al (2005) Exercise and lymphocyte activation following chemotherapy for breast cancer. Med Sci Sports Exerc 37(11):1827–1835CrossRefPubMedGoogle Scholar
  27. 27.
    Gomez AM, Martinez C, Fiuza-Luces C, Herrero F, Perez M, Madero L et al (2011) Exercise training and cytokines in breast cancer survivors. Int J Sports Med 32(6):461–467CrossRefPubMedGoogle Scholar
  28. 28.
    Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51CrossRefPubMedGoogle Scholar
  29. 29.
    Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL et al (2008) Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 300(23):2754–2764CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK et al (2009) American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc 41(2):459–471CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Division of Biokinesiology and Physical Therapy, Ostrow School of DentistryUniversity of Southern California (USC)Los AngelesUSA
  2. 2.Diabetes & Obesity Program and Department of Pediatrics, Children’s Hospital Los AngelesKeck School of Medicine (KSOM)Los AngelesUSA
  3. 3.Department of Medicine, KSOMUSCLos AngelesUSA
  4. 4.Department of Preventive Medicine, KSOMUSCLos AngelesUSA
  5. 5.Division of Pediatric Endocrinology, Mattel Children’s HospitalUniversity of California, Los AngelesLos AngelesUSA

Personalised recommendations