Elevated aromatase in the setting of adipose dysfunction provides a possible mechanism for the higher incidence of hormone-dependent breast cancer in obese women after menopause.

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. .

Excess body fat and sedentary behavior are associated with increased breast cancer risk and mortality, including in normal weight women. To investigate underlying mechanisms, we examined whether adiposity and exercise impact the breast microenvironment (e.g., inflammation and aromatase expression) and circulating metabo-inflammatory factors. In a cross-sectional cohort study, breast white adipose tissue (WAT) and blood were collected from 100 women undergoing mastectomy for breast cancer risk reduction or treatment. Self-reported exercise behavior, body composition measured by dual-energy x-ray absorptiometry (DXA), and waist:hip ratio were obtained prior to surgery. Breast WAT inflammation (B-WATi) was assessed by immunohistochemistry and aromatase expression was assessed by quantitative PCR. Metabolic and inflammatory blood biomarkers that are predictive of breast cancer risk and progression were measured. B-WATi was present in 56/100 patients and was associated with older age, elevated BMI, postmenopausal status, decreased exercise, hypertension and dyslipidemia (Ps<0.001). Total body fat and trunk fat correlated with B-WATi and breast aromatase levels (Ps<0.001). Circulating C-reactive protein, interleukin-6, insulin and leptin positively correlated with body fat and breast

Breast white adipose tissue inflammation (BWATi) is associated with obesity and higher breast cancer (BC) risk among non-Hispanic white women. Obesity is prevalent in Hispanic/Latina BC patients, and the occurrence of BWATi in this population is not well-characterized. The association between BWATi and body mass index (BMI) was evaluated in Hispanic/Latina BC patients who underwent mastectomy. BWATi was defined as the presence of crown-like structures of the breast (CLS-B), detected by CD68 immunohistochemistry in non-tumor breast tissue. BWATi severity was quantified as number of CLS-B/cm2. Adipocyte diameter was measured using hematoxylin and eosin (H&E) stained breast tissue sections. Preoperative BMI (within 1 week prior to mastectomy) was categorized as normal (18.5 to <25.0 kg/m2), overweight (25.0 to <30.0 kg/m2), class I obesity (30.0 to <35.0 kg/m2), and class II-III obesity (35.0 kg/m2 or above). Patient charts were abstracted to record clinicopathologic features and liver function tests <90 days before mastectomy. The study included 91 women (mean age 69 years; range 36–96 years). Prevalence of BWATi increased with BMI (24% in normal weight, 34% in overweight, 57% in class I obesity, and 65% in class II-III obesity; P for trend <0.01). Severe BWATi (>0.27 CLS-B/cm2) was associated with higher BMI (P for trend=0.046) and greater adipocyte diameter (P=0.04). Adjusting for BMI, neoadjuvant chemotherapy and elevated alanine aminotransferase were associated with severe BWATi, and current smoking was associated with mild BWATi (all P<0.05). BWATi was associated with higher BMI in Hispanic/Latina BC patients, consistent with previously described associations in other populations.

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