Abstract Background:Previous studies suggested a link between obesity, insulin-resistance and breast cancer outcome. The aim of the present prospective observational study was to investigate the role of metabolic syndrome (MetS) and its components on early breast cancer (EBC) patients' outcome. Methods: MetS was defined by the presence of 3 to 5 of the following components: waist circumference (WC) > 88 cm, blood pressure ≥ 130/≥85 mmHg, serum levels of triglycerides (TG) ≥ 150 mg/dL, high-density lipoprotein (HDL) < 50 mg/dL and fasting glucose (FG) ≥ 110 mg/ dL (National Cholesterol Education Program Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults - NCEP-ATPIII criteria). Overall, 955 EBC patients were prospectively enrolled between January 2009 and December 2013 at University Hospital Federico II and National Cancer Institute G.Pascale, Naples, Italy. Clinical and tumor characteristics were collected for all the patients. A total of 494 patients (51.7%) had complete data on all the components of MetS at first diagnosis and thus were included in the current analysis. Study population was divided into 2 main groups: (1) patients with less than 3 components (No MetS); (2) patients with 3-5 components (MetS). Categorical variables were analyzed by the chi-square test and survival data by the log-rank test and Cox proportional hazards regression model. Results: Overall 366 (74.1%) and 128 (25.9%) women were categorized as No MetS and MetS, respectively. MetS patients were more likely to be older and postmenopausal compared to No MetS patients. In detail, 46% vs 38% were older than 55 yrs (p<0.0001) and 87% vs 54% were postmenopausal (p<0.0001) in MetS vs No MetS groups, respectively. No statistically significant differences in tumor stage, type of adjuvant therapy or tumor subtypes defined by immunohistochemistry (IHC) were identified among the two groups. At univariate analysis, stage, tumor subtypes, TG and FG values, number of components of MetS, and presence of MetS were significantly associated to both disease free survival (DFS) and overall survival (OS). Age, BMI, WC, and HDL levels were correlated to OS only. At the multivariate Cox proportional hazards model (adjusted for age, menopausal status, stage, IHC subtypes and adjuvant therapy) MetS patients had numerically higher risk of relapse and significantly higher risk of death compared to No MetS patients [DFS hazard ratio (HR): 1.64 95% confidence interval (CI): 0.94-2.86, p=0.07 and OS HR: 3.83, 95% CI 1.7-6.77 p=0.001]. Additionally, of the 366 No MetS patients included in the analysis, 122 (33.3%) had 0 and 244 (66.7%) had “1 to 2” components of MetS. Interestingly, patients with “1 to 2” components of MetS had increased risk of dying compared to patients with 0 components (OS HR: 4.39, 95% CI:1.26-15.36, p=0.02) . No significant difference among these two groups was observed in terms of DFS. Conclusions: MetS is correlated with poor outcome in EBC patients. Among patients without full criteria for MetS diagnosis, the presence of 1 or 2 components of the syndrome may predict for worse survival. Testing for components of MetS in BC patients is recomended to predict outcome and to eventually suggest lifestyle changes, exercise and diet. Citation Format: Buono G, Crispo A, Giuliano M, Rea CG, Forestieri V, Lauria R, De Placido P, De Laurentiis M, Pacilio C, Grimaldi M, Nocerino F, Montella M, De Placido S, Arpino G. Metabolic syndrome and early-stage breast cancer outcome: Results from a prospective observational study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-15.