Obesity and Fibrosis: Setting the Stage for Breast Cancer

SIMPLE SUMMARY: Obesity is a significant risk factor for breast cancer in postmenopausal women. Regardless of menopausal status, women with obesity have an elevated incidence of metastasis and a decreased response to treatment. Understanding how obesity promotes the development and progression of breast cancer could improve interventions for women with obesity. Breast tissue contains fat. In response to obesity, breast tissue fat contains more collagen that surrounds the fat cells and epithelial cells. Supportive cells within the fat increase collagen production, which elevates the stiffness of the tissue. Inflammatory cells called macrophages interact with other supportive cells within the fat to increase collagen in the surrounding breast tissue. While weight loss is recommended to reduce obesity, the long-term effects on improving inflammation and the amount of collagen are less clear. Increased collagen and inflammation within breast tissue may enhance the risk for tumor development and promote characteristics associated with a worsened prognosis. ABSTRACT: Obesity is a rising health concern and is linked to a worsened breast cancer prognosis. Tumor desmoplasia, which is characterized by elevated numbers of cancer-associated fibroblasts and the deposition of fibrillar collagens within the stroma, may contribute to the aggressive clinical behavior of breast cancer in obesity. A major component of the breast is adipose tissue, and fibrotic changes in adipose tissue due to obesity may contribute to breast cancer development and the biology of the resulting tumors. Adipose tissue fibrosis is a consequence of obesity that has multiple sources. Adipocytes and adipose-derived stromal cells secrete extracellular matrix composed of collagen family members and matricellular proteins that are altered by obesity. Adipose tissue also becomes a site of chronic, macrophage-driven inflammation. Macrophages exist as a diverse population within obese adipose tissue and mediate the development of fibrosis through the secretion of growth factors and matricellular proteins and interactions with other stromal cells. While weight loss is recommended to resolve obesity, the long-term effects of weight loss on adipose tissue fibrosis and inflammation within breast tissue are less clear. Increased fibrosis within breast tissue may increase the risk for tumor development as well as promote characteristics associated with tumor aggressiveness.