Metabolic Syndrome and Risk of Breast Cancer by Molecular Subtype: analysis of the MEND study

ABSTRACT Background : Metabolic syndrome (MetS) is characterized by a cluster of biological irregularities. The purpose of this analysis was to examine the association of MetS with BC among Nigerian women, and for the first time evaluate this association by molecular subtype. Methods : MetS was defined as having at least 3 out of 5 of: high blood pressure (≥130/85 mm Hg), reduced HDL ( 150 mg/dL), high waist circumference (≥80 cm), and prior diagnosis of diabetes or elevated fasting glucose level (≥100 mg/dL). Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were utilized to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for the association between MetS and BC overall. Multinomial logistic regression models were used to evaluate each molecular subtype (Luminal A, Luminal B, HER2-enriched and triple-negative or TNBC). Results : After adjusting for age, socio-demographic and reproductive risk factors, there was a positive association between MetS and BC (aOR: 1.84, 95% CI: 1.07, 3.16). In stratified analyses, MetS was associated with BC regardless of BMI status; however, the estimate was significant only among normal weight women (aOR: 3.85; 95% CI: 1.25, 11.90). MetS was significantly associated with TNBC subtype (aOR: 4.37, 95% CI: 1.67, 11.44); associations for other molecular subtypes were not statistically significant. Conclusion : MetS appears to be a robust risk factor for BC, particularly for TNBC. Public health and clinical interventions can provide substantial benefits in reducing the burden of MetS and preventing BC among Nigerian women. MICRO-ABSTRACT : Metabolic syndrome is a cluster of biological irregularities that is a known risk factor for cardiovascular disease, stroke, and diabetes. In a case-control study of 555 Nigerian women, we observed that metabolic syndrome was strongly associated with breast cancer and the aggressive triple-negative molecular subtype, highlighting a need for clinical and lifestyle interventions targeting metabolic syndrome to reduce breast cancer risk in this population.