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Quality and quantity of visceral fat tissue are associated with insulin resistance and survival outcomes after chemotherapy in patients with breast cancer

  • Epidemiology
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Abstract

Purpose

Recent studies suggest that the quality and quantity of visceral adipose tissue (VAT) play significant roles in adipocyte function, and are related to insulin resistance. We tested the hypothesis that high amounts of upper VAT (aVAT) and low-quality VAT worsen treatment outcomes via altered insulin metabolism.

Methods

Cohort 1 included 106 women with breast cancer who were undergoing surgery. Homeostasis model assessment of insulin resistance (HOMA-R), insulin-like growth factor (IGF)-1, and IGF-binding protein 3 (IGFBP3) were measured before the initiation of treatment. aVAT was measured via computed tomography (CT). VAT quality was assessed using CT-determined Hounsfield units (VAT-HU). Associations between the variables investigated and VAT quality and quantity were analyzed. Cohort 2 included 271 patients who underwent chemotherapy. Associations between the variables investigated and survival outcomes after chemotherapy were analyzed via retrospective chart review.

Results

In cohort 1, aVAT was significantly correlated with insulin and HOMA-R levels. As body mass index (BMI) class increased, mean IGF-1 increased and mean IGFBP3 decreased, but these trends were not statistically significant. In cohort 2, aVAT was significantly positively correlated with BMI. The patients in the third aVAT tertiles had significantly shorter distant disease-free survival (dDFS) after neoadjuvant chemotherapy setting. In multivariate analysis, aVAT and VAT-HU were significantly associated with shorter dDFS.

Conclusions

High aVAT and low-quality VAT were associated with poor survival outcome, increased insulin levels, and insulin resistance. The present study suggests the importance of evaluating the quality and quantity of VAT when estimating insulin resistance and treatment outcomes.

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References

  1. Society AC (2018) Breast Cancer Facts & Figures 2017-2018

  2. Cancer Facts & Figures 2018 [Internet] (2018) Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf

  3. Prevalence of Obesity Among Adults and Youth: United States, 2015–2016 [Internet]. 2017. Available from: https://www.cdc.gov/nchs/data/databriefs/db288.pdf

  4. Fontanella C, Lederer B, Gade S, Vanoppen M, Blohmer JU, Costa SD et al (2015) Impact of body mass index on neoadjuvant treatment outcome: a pooled analysis of eight prospective neoadjuvant breast cancer trials. Breast Cancer Res Treat 150(1):127–139

    Article  CAS  Google Scholar 

  5. Iwase T, Nakamura R, Yamamoto N, Yoshi A, Itami M, Miyazaki M (2014) The effect of molecular subtype and body mass index on neo-adjuvant chemotherapy in breast cancer patients. Breast 23(3):264–272

    Article  Google Scholar 

  6. Litton JK, Gonzalez-Angulo AM, Warneke CL, Buzdar AU, Kau SW, Bondy M et al (2008) Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer. J Clin Oncol 26(25):4072–4077

    Article  Google Scholar 

  7. Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Investig 106(4):473–481

    Article  CAS  Google Scholar 

  8. Lewitt MS, Dent MS, Hall K (2014) The insulin-like growth factor system in obesity, insulin resistance and type 2 diabetes mellitus. J Clin Med 3(4):1561–1574

    Article  Google Scholar 

  9. Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. JNCI 92(18):1472–1489

    Article  CAS  Google Scholar 

  10. Cecchini RS, Swain SM, Costantino JP, Rastogi P, Jeong JH, Anderson SJ et al (2016) Body mass index at diagnosis and breast cancer survival prognosis in clinical trial populations from NRG Oncology/NSABP B-30, B-31, B-34, and B-38. Cancer Epidemiol Biomark Prev 25(1):51–59

    Article  Google Scholar 

  11. Erbes T, Stickeler E, Rucker G, Buroh S, Asberger J, Dany N et al (2016) BMI and pathologic complete response to neoadjuvant chemotherapy in breast cancer: a Study and Meta-Analysis. Clin Breast Cancer 16(4):e119–e132

    Article  Google Scholar 

  12. Warner ET, Ballman KV, Strand C, Boughey JC, Buzdar AU, Carey LA et al (2016) Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426). Breast Cancer Res Treat 159(1):109–118

    Article  CAS  Google Scholar 

  13. Denis GV, Obin MS (2013) ‘Metabolically healthy obesity’: origins and implications. Mol Aspects Med 34(1):59–70

    Article  CAS  Google Scholar 

  14. Iwase T, Sangai T, Nagashima T, Sakakibara M, Sakakibara J, Hayama S et al (2016) Impact of body fat distribution on neoadjuvant chemotherapy outcomes in advanced breast cancer patients. Cancer Med 5(1):41–48

    Article  Google Scholar 

  15. Ritter A, Friemel A, Fornoff F, Adjan M, Solbach C, Yuan J et al (2015) Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells. Oncotarget 6(33):34475–34493

    Article  Google Scholar 

  16. Donohoe CL, Doyle SL, Reynolds JV (2011) Visceral adiposity, insulin resistance and cancer risk. Diabetol Metab Syndr 3:12

    Article  Google Scholar 

  17. Catalan V, Gomez-Ambrosi J, Rodriguez A, Ramirez B, Silva C, Rotellar F et al (2011) Up-regulation of the novel proinflammatory adipokines lipocalin-2, chitinase-3 like-1 and osteopontin as well as angiogenic-related factors in visceral adipose tissue of patients with colon cancer. J Nutr Biochem 22(7):634–641

    Article  CAS  Google Scholar 

  18. Divella R, De Luca R, Abbate I, Naglieri E, Daniele A (2016) Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation. J Cancer 7(15):2346–2359

    Article  CAS  Google Scholar 

  19. van Kruijsdijk RC, van der Wall E, Visseren FL (2009) Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomark Prevent 18(10):2569–2578

    Article  Google Scholar 

  20. Rosenquist KJ, Pedley A, Massaro JM, Therkelsen KE, Murabito JM, Hoffmann U et al (2013) Visceral and subcutaneous fat quality and cardiometabolic risk. JACC Cardiovasc Imaging 6(7):762–771

    Article  Google Scholar 

  21. Cote JA, Nazare JA, Nadeau M, Leboeuf M, Blackburn L, Despres JP et al (2016) Computed tomography-measured adipose tissue attenuation and area both predict adipocyte size and cardiometabolic risk in women. Adipocyte 5(1):35–42

    Article  CAS  Google Scholar 

  22. Hu HH, Chung SA, Nayak KS, Jackson HA, Gilsanz V (2011) Differential computed tomographic attenuation of metabolically active and inactive adipose tissues: preliminary findings. J Comput Assist Tomogr 35(1):65–71

    Article  Google Scholar 

  23. Green MC, Buzdar AU, Smith T, Ibrahim NK, Valero V, Rosales MF et al (2005) Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol 23(25):5983–5992

    Article  CAS  Google Scholar 

  24. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2014) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 138(2):241–256

    Article  Google Scholar 

  25. Edge SBBD, Compton CC, Fritz AG, Greene FL, Trotti A (2009) American Joint Committee on cancer staging manual, 7th edn. Spinger, New York

    Google Scholar 

  26. Lee JJ, Pedley A, Hoffmann U, Massaro JM, Fox CS (2016) Association of changes in abdominal fat quantity and quality with incident cardiovascular disease risk factors. J Am Coll Cardiol 68(14):1509–1521

    Article  Google Scholar 

  27. Item F, Konrad D (2012) Visceral fat and metabolic inflammation: the portal theory revisited. Obes Rev 13(Suppl 2):30–39

    Article  Google Scholar 

  28. Shen W, Punyanitya M, Wang Z, Gallagher D, St-Onge MP, Albu J et al (2004) Visceral adipose tissue: relations between single-slice areas and total volume. Am J Clin Nutr 80(2):271–278

    Article  CAS  Google Scholar 

  29. van der Kooy K, Seidell JC (1993) Techniques for the measurement of visceral fat: a practical guide. Int J Obes Relat Metab Disord 17(4):187–196

    PubMed  Google Scholar 

  30. Shen W, Wang Z, Punyanita M, Lei J, Sinav A, Kral JG et al (2003) Adipose tissue quantification by imaging methods: a proposed classification. Obes Res 11(1):5–16

    Article  Google Scholar 

  31. Doyle SL, Donohoe CL, Lysaght J, Reynolds JV (2012) Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc 71(1):181–189

    Article  CAS  Google Scholar 

  32. Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8(12):915–928

    Article  CAS  Google Scholar 

  33. Lee JJ, Pedley A, Hoffmann U, Massaro JM, Keaney JF Jr, Vasan RS et al (2016) Cross-sectional associations of computed tomography (CT)-derived adipose tissue density and adipokines: the Framingham Heart Study. J Am Heart Assoc 5(3):e002545

    PubMed  PubMed Central  Google Scholar 

  34. Ohtomo K, Baron RL, Dodd GD 3rd, Federle MP, Miller WJ, Campbell WL et al (1993) Confluent hepatic fibrosis in advanced cirrhosis: appearance at CT. Radiology 188(1):31–35

    Article  CAS  Google Scholar 

  35. Odegaard JI, Chawla A (2008) Mechanisms of macrophage activation in obesity-induced insulin resistance. Nat Clin Pract Endocrinol Metab 4(11):619–626

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the patients who participated in this research. We also thank Owen Proudfoot, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This research project was funded by the Japanese Society for the Promotion of Science (KAKENHI; Grant No. JP16K19887).

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Correspondence to Toshiaki Iwase.

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

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

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Iwase, T., Sangai, T., Fujimoto, H. et al. Quality and quantity of visceral fat tissue are associated with insulin resistance and survival outcomes after chemotherapy in patients with breast cancer. Breast Cancer Res Treat 179, 435–443 (2020). https://doi.org/10.1007/s10549-019-05467-7

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