Improving risk assessment of obesity-associated breast cancer.

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1544 Background: Elevated body mass index (BMI) is associated with increased risk of estrogen receptor (ER)-positive postmenopausal breast cancer. The risk is also elevated in women with a normal BMI but excess body fat. These risks may be driven by breast white adipose tissue inflammation (WATi), which is associated with elevated aromatase levels and systemic metabolic dysfunction (e.g. hyperinsulinemia). We hypothesized that body fat assessment is superior to BMI for detecting the pathophysiology that promotes obesity-related breast cancer, particularly among normal BMI women. Methods: Non-tumorous breast tissue was collected from women undergoing mastectomy for breast cancer treatment or prevention. Breast WATi was detected by the presence of crown-like structures in the breast, which are composed of a dead/dying adipocyte surrounded by CD68+ macrophages. Body composition was measured prior to mastectomy via dual energy X-ray absorptiometry. Exercise behavior was also assessed prior to surgery using the Godin Leisure Time Exercise Questionnaire. Associations among categorical variables were examined using Χ2 or Fisher’s exact test. Relationships between continuous variables were examined using the Spearman correlation. Results: From April 5, 2016 to August 31, 2018, 100 patients were enrolled; median age 49 (range 29 to 82) years. Breast WATi was present in 56/100 (56%) women and was associated with elevated BMI and body fat levels, breast adipocyte hypertrophy, postmenopausal status, metabolic syndrome and decreased physical activity (P < 0.05). Among 39 women with normal BMI, breast WATi was present in 14 (36%) and was associated with elevated body fat levels, breast adipocyte hypertrophy, dyslipidemia, and decreased physical activity (P < 0.05). There was no statistically significant association between BMI and breast WATi in the normal BMI group. Menopausal status and total fat mass had greater sensitivity and specificity for the detection of breast WATi compared to a BMI-based model (AUC 0.843 vs. 0.779, respectively). Conclusions: Measurement of body fat is superior to BMI for predicting breast inflammation, which has been shown to promote obesity-related breast cancer.