Crown-Like Structures in Breast Adipose Tissue: Early Evidence and Current Issues in Breast Cancer

Abstract

Obesity is an established risk factor for postmenopausal breast cancer and has been linked to worse breast cancer prognosis, most clearly for hormone receptor-positive breast cancers. The underlying mechanisms of the obesity–breast cancer association are not fully understood, but growing evidence points to the breast adipose tissue microenvironment playing an important role. Obesity-induced adipose tissue dysfunction can result in a chronic state of low-grade inflammation. Crown-like structures of the breast (CLS-B) were recently identified as a histologic marker of local inflammation. In this review, we evaluate the early evidence of CLS-B in breast cancer. Data from preclinical and clinical studies show that these inflammatory lesions within the breast are associated with local NF-κB activation, increased aromatase activity, and elevation of pro-inflammatory mediators (TNFα, IL-1β, IL-6, and COX-2-derived PGE2)—factors involved in multiple pathways of breast cancer development and progression. There is also substantial evidence from epidemiologic studies that CLS-B are associated with greater adiposity among breast cancer patients. However, there is insufficient evidence that CLS-B impact breast cancer risk or prognosis. Comparisons across studies of prognosis were complicated by differences in CLS-B evaluation and deficiencies in study design, which future studies should take into consideration. Breast adipose tissue inflammation provides a plausible explanation for the obesity–breast cancer association, but further study is needed to establish its role and whether markers such as CLS-B are clinically useful.