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

Abstract

Simple SummaryObesity increases the risk of postmenopausal, hormone receptor-positive breast cancer and has been linked to a higher risk of recurrence and mortality. During obesity, adipose tissue can become dysfunctional, resulting in chronic low-grade inflammation. Crown-like structures in breast adipose tissue (CLS-B), composed of macrophages surrounding dead or dying adipocytes in a crown-like pattern, are a new histologic marker of local inflammation. In this review, we aim to evaluate the early evidence of CLS-B in breast cancer. There is consistent evidence that CLS-B are more frequently detected among obese compared to non-obese breast cancer patients. Additionally, several studies have found that CLS-B presence is associated with metabolic and inflammatory factors that contribute to breast cancer development and progression. However, more studies are needed to understand the potential clinical utility of CLS-B as a marker of breast cancer risk or prognosis.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.