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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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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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Authors and Affiliations

  1. Department of Breast Medical Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Toshiaki Iwase

  2. Department of General Surgery, Chiba Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan

    Toshiaki Iwase, Takafumi Sangai, Hiroshi Fujimoto, Ayako Nakagawa, Takahito Masuda, Takeshi Nagashima & Masayuki Ohtsuka

  3. Department of Laboratory Medicine, Chiba Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan

    Yuji Sawabe & Kazuyuki Matsushita

  4. Department of Global Clinical Research, Chiba Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan

    Kengo Nagashima & Yasunori Sato

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  1. Toshiaki Iwase
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  2. Takafumi Sangai
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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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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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