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. 2020 Jan;179(2):435-443. doi: 10.1007/s10549-019-05467-7. Epub 2019 Oct 16.

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.

Keywords: Breast neoplasm; Intra-abdominal fat; Neoadjuvant therapy; Obesity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Body Mass Index
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / metabolism
  • Female
  • Humans
  • Insulin Resistance*
  • Intra-Abdominal Fat*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Biomarkers