Effects of Adiposity and Exercise on Breast Tissue and Systemic Metabo-Inflammatory Factors in Women at High Risk or Diagnosed with Breast Cancer

Abstract

Excess body fat and sedentary behavior are associated with increased breast cancer risk and mortality, including in normal weight women. To investigate underlying mechanisms, we examined whether adiposity and exercise impact the breast microenvironment (e.g., inflammation and aromatase expression) and circulating metabo-inflammatory factors. In a cross-sectional cohort study, breast white adipose tissue (WAT) and blood were collected from 100 women undergoing mastectomy for breast cancer risk reduction or treatment. Self-reported exercise behavior, body composition measured by dual-energy x-ray absorptiometry (DXA), and waist:hip ratio were obtained prior to surgery. Breast WAT inflammation (B-WATi) was assessed by immunohistochemistry and aromatase expression was assessed by quantitative PCR. Metabolic and inflammatory blood biomarkers that are predictive of breast cancer risk and progression were measured. B-WATi was present in 56/100 patients and was associated with older age, elevated BMI, postmenopausal status, decreased exercise, hypertension and dyslipidemia (Ps<0.001). Total body fat and trunk fat correlated with B-WATi and breast aromatase levels (Ps<0.001). Circulating C-reactive protein, interleukin-6, insulin and leptin positively correlated with body fat and breast

Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis

“…Moreover, we detected ERBB4 signaling as one of the topmost significant pathways shared by CRP/IL6 and BC development; this finding is supported by previous studies reporting that (a) human pro-inflammatory macrophages stimulating CRP/IL6 production induces ERBB4 expression and (b) CRP/IL6 correlates with breast tissue aromatase levels in women diagnosed with BC and those with a high risk of BC [61]. Finally, ERBB4 has been inhibited as a therapeutic target for BC by pan-ERBB tyrosine kinase inhibitors such as lapatinib [62].…”

Overview of the molecular mechanisms contributing to the formation of cancer‑associated adipocytes (Review)

“…TNF-α can also upregulate miRNA-130 expression via the NF-κB pathway, which acts synergistically with Wnt10b to inhibit the transcription of PPARγ and dedifferentiate adipocytes. ( 6 ) Tumor-derived miR-105 activates MYC signaling and induces metabolic changes in adipocytes. miR-122 reduces the inhibitory effect of GEPK on glucose uptake.…”

“…Adipocytes, preadipocytes, fibroblasts, immune cells, endothelial cells and extracellular matrix (ECM) are the main components of adipose tissue, which is divided into white, brown and beige adipose tissue ( 4 , 5 ). White adipocytes are the most abundant fat cells in the human body, and previous findings have associated white adipose tissue (WAT) with an increased risk of breast cancer ( 6 ). In addition to serving as an energy reservoir for triglycerides, adipose tissue is an active endocrine organ that secretes hormones, adipokines, cytokines, chemokines and proinflammatory molecules ( 7 ).…”

Cancer Evo–Dev: A Theory of Inflammation-Induced Oncogenesis

“…Pollution, metabolic syndrome, physical inactivity, and adverse psychosocial exposure also promote the development of cancers via inducing chronic low-grade inflammation (41)(42)(43)(44)(45)(46)(47)(48)(49). Environmental and psychosocial factors and nutrition contribute mostly, either with a causative or a promotional role to increased low-grade smoldering chronic inflammation, especially in aged population (44).…”

“…The development of metabolic syndrome is attributed to the chronic low-grade inflammation that occurs in metabolic tissues including the liver (45). People with glucose intolerance, sedentary behavior, obesity, and lower physical activity levels have higher levels of circulating inflammatory factors that have been associated with increased risks of different cancer types (liver, endometrial, colorectal, esophageal, renal, pancreatic, gastric cardia, ovarian, meningioma, postmenopausal breast, multiple myeloma, gallbladder, thyroid, and lung) (46)(47)(48). Inflammation can be classified as "good" and "bad" inflammation.…”