Association between metabolic syndrome and mortality among breast cancer survivors: a prospective cohort study

Metabolic syndrome (MetS) has been associated with elevated mortality risk and cardiovascular disease incident among the general population. However, evidence on its impact among breast cancer (BC) survivors remains limited.

BC survivors in the UK Biobank, a large-scale, population-based prospective cohort, were included in this study. MetS was defined as fulfilling at least three of the following criteria: (1) central obesity, (2) elevated triglycerides or taking lipid-lowering medication, (3) increased blood pressure, (4) elevated fasting blood glucose, and (5) reduced HDL cholesterol. The primary outcome was all-cause mortality, while the secondary outcomes were comorbidity incident. The associations between MetS with mortality and comorbidity incident were determined using Cox proportional regression by quantifying the hazard ratio (HR) and its 95% confidence interval (CI).

After a median follow-up of 15.7 (interquartile range, 15.1 to 16.4) years, a total of 1,251 deaths were observed among 6,027 BC survivors, of whom 1,997 (33.1%) had MetS. MetS was significantly associated with all-cause mortality (HR, 1.23; 95% CI, 1.08 to 1.41, p = 0.002). Meanwhile, MetS was also significantly associated with elevated risk of myocardial infarction (MI; HR, 1.56; 95% CI, 1.02 to 2.40), atrial fibrillation (AF; HR, 1.61; 95% CI, 1.04 to 2.49), and chronic kidney disease (CKD; HR, 1.98 95% CI, 1.56 to 2.51) incident. Fatty acid metabolism and inflammation were identified as the potential mediating factors between MetS and mortality.

MetS was significantly associated with elevated mortality risk and incident of MI, AF, and CKD. The MetS-mortality association was potentially mediated by fatty acid metabolism and inflammation. Findings highlighted MetS as a potentially modifiable risk factor in BC survivors, underscoring the need for targeted metabolic management to improve long-term outcomes.