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

  • Toshiaki IwaseEmail author
  • Takafumi Sangai
  • Hiroshi Fujimoto
  • Yuji Sawabe
  • Kazuyuki Matsushita
  • Kengo Nagashima
  • Yasunori Sato
  • Ayako Nakagawa
  • Takahito Masuda
  • Takeshi Nagashima
  • Masayuki Ohtsuka



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.


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.


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.


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.


Breast neoplasm Intra-abdominal fat Neoadjuvant therapy Obesity 



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


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

Compliance with ethical standards

Conflict of interest

The authors 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 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.

Supplementary material

10549_2019_5467_MOESM1_ESM.doc (464 kb)
Supplementary material 1 (DOC 464 kb)
10549_2019_5467_MOESM2_ESM.doc (92 kb)
Supplementary material 2 (DOC 92 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Toshiaki Iwase
    • 1
    • 2
    Email author
  • Takafumi Sangai
    • 2
  • Hiroshi Fujimoto
    • 2
  • Yuji Sawabe
    • 3
  • Kazuyuki Matsushita
    • 3
  • Kengo Nagashima
    • 4
  • Yasunori Sato
    • 4
  • Ayako Nakagawa
    • 2
  • Takahito Masuda
    • 2
  • Takeshi Nagashima
    • 2
  • Masayuki Ohtsuka
    • 2
  1. 1.Department of Breast Medical OncologyMD Anderson Cancer CenterHoustonUSA
  2. 2.Department of General SurgeryChiba Graduate School of MedicineChibaJapan
  3. 3.Department of Laboratory MedicineChiba Graduate School of MedicineChibaJapan
  4. 4.Department of Global Clinical ResearchChiba Graduate School of MedicineChibaJapan

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