Inflammation of mammary adipose tissue occurs in overweight and obese patients exhibiting early-stage breast cancer

Abstract

Growing evidence indicates that adiposity is associated with breast cancer risk and negatively affects breast cancer recurrence and survival, a paracrine role of mammary adipose tissue being very likely in this process. In contrast to other adipose depots, occurrence of a sub-inflammatory state of mammary adipose tissue defined by dying adipocytes surrounded by macrophages forming crown-like structures in overweight and obese subjects, remains only partially described. In a general population of breast cancer patients (107 patients) mostly undergoing breast-conserving surgery, we found a positive association between patient’s body composition, breast adipocytes size, and presence of crown-like structures in mammary adipose tissue close to the tumor. Overweight (BMI: 25.0–29.9 kg/m2) and obese (BMI ≥ 30.0 kg/m2) patients have 3.2 and 6.9 times higher odds ratio of crown-like structures respectively, compared with normal weight patients. The relatively small increase in adipocyte size in crown-like structures positive vs. negative patients suggests that mammary adipose tissue inflammation might occur early during hypertrophy. Our results further highlight that body mass index is an adequate predictor of the presence of crown-like structures in mammary adipose tissue among postmenopausal women, whereas in premenopausal women truncal fat percentage might be more predictive, suggesting that mammary adipose tissue inflammation is more likely to occur in patients exhibiting visceral obesity. Finally, the presence of crown-like structures was positively associated with systemic markers such as the Triglyceride/High-density lipoprotein-cholesterol ratio serum C-reactive protein and glucose/(HbA1c) glycated Haemoglobin. These compelling results demonstrate that excess adiposity, even in overweight patients, is associated with mammary adipose tissue inflammation, an event that could contribute to breast cancer development and progression.

Obesity‐induced MBD2_v2 expression promotes tumor‐initiating triple‐negative breast cancer stem cells

“…Activation of breast cancer cell IFNc receptors increases ROS levels, specifically hydrogen peroxide (Zibara et al, 2017). Also in obese breast cancer patients, increased macrophage infiltration of breast adipose tissue yields additional paracrine-acting pro-inflammatory cytokines (Vaysse et al, 2017).…”

Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk

“…Moreover, adipocytes and visceral adipose tissues produce leptin and adiponectin, which are hormones that have the capacity to modulate immune function, inflammatory cytokines, angiogenesis, insulin resistance, and other biological processes that are associated with cancer initiation and progression [46]. High levels of leptin attract monocytes and promote monocyte differentiation to macrophages that produce TNF-α, fibroblast growth factor, and epidermal growth factor, which promote angio-genesis in developing tumors [47].…”

Metabolically activated macrophages in mammary adipose tissue link obesity to triple-negative breast cancer

“…In addition to inflammation at metastatic sites, obesity also promotes local inflammation in adipose tissue which is mediated by macrophage infiltration and activation (Xu et al, 2003;Lumeng and Saltiel, 2011). Obesity-induced inflammation in mammary adipose tissue (Howe et al, 2013;Vaysse et al, 2017) may be of particular significance because breast cancers form in this niche and inflammation promotes stem-like properties in cancer cells and an increased propensity to form tumors (Grivennikov et al, 2010). Thus, pro-inflammatory macrophage accumulation in mammary fat may augment TNBC tumor formation during obesity.…”