P0008 Validating the link between obesity and breast inflammation in women with breast cancer

Abstract

Background In post-menopausal women, obesity is a risk factor for hormone sensitive breast cancer. We previously described crown-like structures (CLS), consisting of macrophages surrounding dead adipocytes, in the breast tissues of mice and humans. CLS were associated with increased levels of proinflammatory mediators known to be involved in carcinogenesis. We provided the first evidence of CLS in the human breast (CLS-B), which correlated with increased aromatase expression and activity. Here, we expanded our population to prospectively validate these preliminary findings. Methods White adipose tissue (WAT) was prospectively collected from women undergoing breast and reconstructive surgery. WAT was subjected to immunohistochemistry for CD68, a macrophage marker, to detect CLS-B by light microscopy. Adipocyte diameter was measured using the Canvas 11 Software. Endpoints were CLS-B presence/absence and CLS-B index (proportion of slides with CLS-B). Findings From April 2010 to February 2012, WAT (100 mastectomy and five abdominal reconstructions) was obtained from 101 American women; median age 49 years (range 26–80). CLS-B were found in 54 (53%) patients. CLS-B were seen in 9/37 (24%) normal weight patients (body mass index [BMI] μ m) compared with those without CLS-B (91.5 ± 16.1 μm; p p = 0.04). Among 25 patients with bilateral breast WAT and five patients with paired breast and abdominal WAT, concordant CLS-B findings (+/–) were seen in 80%. Interpretation Findings from this prospective study confirm that CLS-B are associated with BMI and adipocyte size. These results provide a plausible pathophysiological link between obesity and breast cancer. Abdominal WAT may be a surrogate for breast WAT inflammation; biopsies of abdominal subcutaneous WAT are more easily done, and could be performed in future clinical trials that aim to decrease breast WAT inflammation.