Central Obesity, Body Mass Index, Metabolic Syndrome and Mortality in Mediterranean Breast Cancer Patients

Abstract Background: Obesity and metabolic disorders have been associated with poorer outcomes in many cohorts of breast cancer (BC) patients, with poor evidence from Mediterranean cohorts. The purpose of this study is to investigate the prognostic potential of anthropometric variables in early BC patients living in a Southern region of Italy. Methods: This prospective cohort study enrolled 955 consecutive early BC patients treated at the Istituto Nazionale dei Tumori “G. Pascale” and at the University Hospital “Federico II”, Naples, Italy, between January 2009 and December 2013. Median follow-up was 11.8 years and ended on June 15 th 2022. Anthropometric measurements and indices namely body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), as well as Metabolic Syndrome (MetS) and its components, were collected. All-cause and BC-specific mortality were calculated. Results: Mean age was 55.3 years (±12.5 years); 61% of patients were post-menopausal. At data cut-off, 208 (22%) patients had died, 131 (14%) of whom from BC. Obesity was found in 29% of patients. High WC or WHR and the presence of MetS were associated with a moderately increased risk of all-cause mortality (WC ≥ 88 cm, HR=1.39, 95%CI:1.00-1.94; WHR > 0.85, HR=1.62, 95%CI:1.12-2.37; MetS, HR=1.61, 95%CI:1.12-2.32). An increased BC-specific mortality risk was found in obese patients (HR=1.72, 95%CI:1.06-2.78), in those with WC ≥88 (HR=1.71, 95%CI:1.12-2.61)and in those with high WHR, both when evaluated as a categorical variable (WHR>0.85, HR=1.80, 95%CI:1.13-2.86) and as a continuous variable (for each 0.1-U increase in WHR, HR=1.33, 95%CI:1.08-1.63) as well as the presence of MetS (HR=1.81, 95%CI:1.51-2.85). These associations varied according to menopausal status and BC subtype. Conclusions: Central obesity significantly increased total and BC-specific mortality particularly in pre-menopausal women, while in post-menopause the MetS was a stronger risk factor. These associations were significant mainly in luminal subtypes while no relevant findings were observed in TNBC. The magnitude of risk suggests that obesity and the presence of the MetS or its single components may nullify the benefit of effective BC therapies. Active lifestyle intervention studies should be encouraged for several expected beneficial effects.