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Visceral Fat and Clinical Outcomes in Breast Cancer

1/14/2020 4:12:50 PM
fatObesity is strongly associated with the development of breast cancer, resistance to treatment, and poor survival outcomes. Women with higher body mass indexes (BMIs) tend to have increased accumulation of free fatty acids in the liver and insulin resistance. Insulin resistance activates the production of insulin-like growth factor (IGF), which in turn can promote cancer cell growth and proliferation.
 
However, not all women with a high BMI exhibit disrupted metabolic function. The “obesity paradox” refers to the fact that some women who are obese, based on their BMI, maintain normal metabolic function. Recent research suggests that the paradox might be explained by differences in body composition and the function of fat tissue.

Many factors involved in fat quality

Visceral adipose tissue (VAT) exhibits unique endocrine functions and produces not only IGF but also adipocytokines and other pro-inflammatory cytokines that might promote cancer. Moreover, the microenvironment of VAT, which consists of the adipose cells, stromal cells, immune cells, and a vascular fraction, influences its endocrine function and fat “quality.”
 
In a study published in Breast Cancer Research and Treatment in October of 2019, researchers explored whether high amounts of upper VAT or low-quality VAT are associated with insulin resistance or poor treatment outcomes in patients with breast cancer.

Study examines relationship between fat, metabolic processes

Most body composition studies rely on single-slice computed tomography (CT) scans to calculate the visceral fat volume. The current study relied on more advanced 3D software to assess upper VAT volume—from the sternal end to the naval. Also, VAT quality was calculated at the naval and reported in Hounsfield units (HU). Results were reported for 2 separate cohorts of women.
 
Cohort 1 consisted of 106 women undergoing surgery for breast cancer. The results showed that higher upper VAT volume and lower VAT quality were both strongly correlated with insulin level and insulin resistance (i.e., HOMA-IR) (p<0.05). However, neither of these variables was related to levels of IGF-1. C-reactive protein was additionally positively associated with insulin level (r = 0.33, p < 0.05) and HOMA-IR (r = 0.34, p < 0.05).
 
Cohort 2 consisted of 271 women undergoing chemotherapy. For those receiving neoadjuvant chemotherapy, higher upper VAT volume and lower VAT quality were significantly associated with poorer survival outcomes after chemotherapy (defined as distant disease-free survival) (p<0.05).
 
The results of this study support the hypothesis that the quantity and quality of visceral fat influence insulin resistance and survival outcomes after chemotherapy. This information contributes to a better understanding of the mechanisms involved in obesity-related treatment resistance in women with breast cancer.   
 
Reference
Iwase, T, T Sangai, H Fujimoto, Y Sawabe, K Matsushita, K Nagashima, Y Sato, A Nakagawa, T Masuda, T Nagashima, and M Ohtsuka. “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 (2019).