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 ( = 72), breast WAT inflammation was present in 31 (43%) women and was associated with elevated BMI ( < 0.01) and increased levels of body fat ( < 0.01), C-reactive protein ( = 0.02), triglycerides ( < 0.01), insulin resistance scores ( = 0.04), and lower HDL cholesterol ( < 0.01). ER tumors were associated with greater body fat versus other subtypes ( = 0.03). Compared with U.S. Caucasians ( = 267), Taiwanese women had larger breast adipocytes despite lower BMI after adjusting for BMI and menopausal status ( = 0.01). A subclinical inflammatory state associated with increased adiposity and metabolic dysfunction could contribute to breast cancer pathogenesis in Asian women. .

Breast Cancer in Lean Postmenopausal Women Might Have Specific Pathological Features

“…Lyengar et al recently reported the very interesting findings that menopausal Taiwanese women had pathologically enlarged adipocytes in breast tissue, meaning that more inflammation was involved, despite having a lower BMI than Caucasian women in the United States (22). Our data showed lean patients to more frequently have high-density breast tissue, reflecting lower adipose tissue contents.…”

BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment

“…New research is forcing consideration of the disturbing possibility that “obesity‐associated” breast cancer is rising worldwide in women who are not apparently obese. Within the last year, work has shown that certain lean women show elevated biomarkers of inflammation both systemically and locally in breast adipose tissue, which associate with increased aromatase and breast cancer risk . These insights provoke a radical hypothesis: obesity per se is less important for cancer risk than metabolic inflammation , which need not accompany expanded fat depots or elevated body mass at all.…”

Hybrid Dietary-Blood Inflammatory Profiles and Postmenopausal Breast Cancer: A Case-Control Study

“…There are a variety of inflammatory biomarkers, which may be involved in carcinogenesis [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. One of the major pro-inflammatory cytokines produced by cells in inflamed tissue is Interleukin-6 (IL-6) [ 7 , 8 , 9 , 10 ]. IL-6 has an important role in chronic inflammatory diseases and may play a role in cancer development [ 7 , 8 , 9 , 10 ].…”

“…One of the major pro-inflammatory cytokines produced by cells in inflamed tissue is Interleukin-6 (IL-6) [ 7 , 8 , 9 , 10 ]. IL-6 has an important role in chronic inflammatory diseases and may play a role in cancer development [ 7 , 8 , 9 , 10 ]. However, the current evidence of the link between the IL-6 and BC risk is insufficient [ 7 , 8 ].…”

“…However, the current evidence of the link between the IL-6 and BC risk is insufficient [ 7 , 8 ]. The next, widely used marker of systemic inflammation is non-specific C-reactive protein (CRP), hepatic-synthesized in response to pro-inflammatory cytokines [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. CRP has been recognised as a risk factor for BC in epidemiologic studies [ 18 , 19 ].…”