Excess body weight significantly affects systemic and tumor inflammatory status and correlates to poor prognosis parameters in patients with breast cancer

Abstract

Introduction: Obesity is a pro-inflammatory disease critical for developing breast cancer (BC), which impacts the profiles of systemic inflammatory mediators and determinants of different disease clinical outcomes remains little explored. Methods: A total of 195 patients diagnosed with breast cancer were included. Aiming to exclude chemotherapy interference on circulating mediators, samples were collected at diagnosis, out of the treatment period. Patients were classified as normal weight (BMI up to 24.9 kg/m2) or overweight (BMI ≥25.0 kg/m2). Serum levels of IL- 4, IL-12, hydroperoxides, and nitric oxide metabolites (NOx) were measured. Also, tumor expression of inducible nitric oxide synthase (iNOS), TGF-β1, CD4+, and CD8+ lymphocytes were evaluated. Results: IL-4 levels were significantly increased in the overweight BC group (p = 0.0329), including patients with luminal B subtype (p = 0.0443), presence of lymph node metastases (p = 0.0115) and age of diagnosis below 50 years, (p = 0.0488). IL-12 levels were significantly increased in overweight BC patients with lymph node metastases (p = 0.0115). Hydroperoxides were increased in overweight BC patients (p = 0.0437), including those with tumors smaller than 2 cm (p = 0.05). NOx levels were also increased in overweight BC patients, including those with luminal B disorders (p = 0.0443), high-grade tumors (p = 0.0351) and lymph node metastases (p = 0.0155). The expression of iNOS (p < 0.001) and TCD4+ lymphocytes (p = 0.0378) was significantly investigated in tumor biopsies from overweight BC women. Conclusions: These data provide a picture of the influence of excess body weight on inflammatory mediators’ systemic and tumoral profiles, especially in patients displaying poor outcome BC.