Adiposity, Inflammation, and Breast Cancer Pathogenesis in Asian Women

Abstract

Obesity is associated with white adipose tissue (WAT) inflammation in the breast, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that predispose to breast cancer development. We examined whether WAT inflammation and its associated systemic effects correlate with body fat levels in an Asian population where body mass index (BMI) is not an accurate assessment of obesity and cancer risk. We also investigated whether biologic differences could account for the greater proportion of premenopausal estrogen receptor (ER)-positive breast cancer in Asian versus Western countries. Breast WAT and fasting blood were prospectively collected from Taiwanese women undergoing mastectomy for breast cancer treatment. Body composition was measured in a subgroup using bioelectrical impedance analysis. WAT inflammation was defined by the presence of crown-like structures of the breast, which are composed of dead or dying adipocytes surrounded by macrophages. Findings were compared with U.S. Caucasian women. In the Taiwanese cohort (n = 72), breast WAT inflammation was present in 31 (43%) women and was associated with elevated BMI (P < 0.01) and increased levels of body fat (P < 0.01), C-reactive protein (P = 0.02), triglycerides (P < 0.01), insulin resistance scores (P = 0.04), and lower HDL cholesterol (P < 0.01). ER⁺ tumors were associated with greater body fat versus other subtypes (P = 0.03). Compared with U.S. Caucasians (n = 267), Taiwanese women had larger breast adipocytes despite lower BMI after adjusting for BMI and menopausal status (P = 0.01). A subclinical inflammatory state associated with increased adiposity and metabolic dysfunction could contribute to breast cancer pathogenesis in Asian women. Cancer Prev Res; 11(4); 227-36. ©2017 AACR.

Figure 1. Study flow diagram

Abbreviations: NTUH, National Taiwan University Hospital; WAT, white adipose tissue; BIA, bioelectrical impedance analysis

Figure 2. Obesity, adiposity, and inflammation in Taiwanese women with breast cancer

A. Anti-CD68 immunostaining showing CLS-B (arrow; 200×). B. Prevalence of WAT inflammation (CLS-B) by BMI category using standard and Asian BMI cutoffs. C. Body fat percentage is highest in Taiwanese women with HR+/HER2– breast cancer (n=31) versus women with HER2+ (n=10) and triple negative (n=3) tumors (P=0.03). D. Higher BMI correlates with larger breast adipocyte size (ρ=0.43, P=0.01). E. Higher body fat percentage correlates with larger breast adipocyte size (ρ=0.52, P<0.01). F. Taiwanese women with WAT inflammation have larger breast adipocytes than those without inflammation (P<0.01). G. Median BMI was lower in the Taiwanese cohort versus US Caucasian cohort (P<0.01). H. Median breast adipocyte size was larger in the Taiwanese cohort versus US Caucasian cohort after adjustment for BMI and menopausal status (P=0.01). Abbreviations: CLS-B, crown-like structures of breast; WAT, white adipose tissue; BMI, body mass index; Nm/Uw, normal/underweight; Ow, overweight; Ob, obese; HR, hormone receptor; HER2, human epidermal growth factor receptor-2