Background: Obesity and insulin resistance are associated with inferior levels of chemosensitivity and overall prognosis for breast cancer (BC) treatment. Recent studies suggest that the quality and quantity of visceral adipose tissue (VAT) play a significant role in adipocyte function, and are related to insulin resistance. We therefore tested the hypothesis that high amount and low quality of VAT worsen treatment outcomes via insulin resistance mechanisms.

Patients and Methods: We examined two independent studies: a cross-sectional study (cohort 1) and a retrospective study (cohort 2). Cohort 1 included 106 women with early-stage BC who were undergoing surgery. Patients with normal weight (17.5< body mass index [BMI, kg/m2] ≤25, n = 53) and overweight/obese patients (BMI >25, n = 53) were selected by a pair-matching method. Insulin resistance was evaluated by HOMA-R: fasting insulin (microU/L) × fasting glucose (nmol/L)/22.5. And insulin-like growth factor (IGF) family including IGF-1 and IGF-binding protein 3 (IGFBP3) were measured before beginning treatment. The amounts of visceral fat (aVAT) was measured by 3-dimensional volumetric software using the stocked computed tomography (CT) imaging data. The quality of VAT was assessed based on the mode value of CT Hounsfield Unit of VAT (VAT-HU) at navel level of CT axial view. The association between the former variables and the quality and quantity of VAT was analyzed. Cohort 2 included 271 patients who received chemotherapy in the neo-adjuvant (NAC) or adjuvant setting. Imaging analysis was performed in the same way, and the association between those values and survival outcome after chemotherapy was analyzed by retrospective chart review.

Results: In cohort 1, aVAT was significantly correlated with serum insulin and HOMA-R levels (Pearson's R 0.44 and 0.42, respectively; P<0.05). On comparing the two groups divided by BMI, the levels of IGF-1 and IGFBP3 were not significantly different between the normal weight and the overweight/obese groups (P = 0.31 and 0.77, respectively). However, the overweight/obese group demonstrated significantly higher HOMA-R (P<0.05). In cohort 2, aVAT was significantly correlated with BMI (P<0.05). In a multivariate analysis, pathological complete responses were not associated with aVAT (P = 0.60). After a median follow-up of 112 months, tertile stratification revealed that the third tertile of aVAT had a significantly shorter distant disease free survival (DDFS) in the NAC setting (p<0.05). When adjusted by covariates in the Cox proportional regression model, aVAT and VAT-HU demonstrated significant contribution to a worsened DDFS ([p<0.05, hazard ratio {HR} 1.39; 95% confidence interval {CI} 1.11 to 1.75] and [p<0.05, HR 1.20, 95% CI 1.01 to 1.43], respectively).

Conclusions: Our study found that high amounts and low quality of VAT worsen treatment outcomes. Furthermore, we found that insulin resistance was related to those two factors. Although further validation is needed, our present work suggests the importance of evaluating the quality and quantity of visceral fat for estimating insulin resistance and treatment outcomes after chemotherapy for patients with early-stage BC.

Citation Format: Iwase T, Sangai T, Nagashima T, Sakakibara M, Fujimoto H, Sawabe Y, Nagashima K, Otsuka M. The quality and quantity of visceral fat tissue are associated with insulin resistance and survival outcome after chemotherapy for patients with early-stage breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-23.