Metabolic syndrome and risks of breast cancer outcomes for luminal, triple-negative, and HER2-overexpressing subtypes

Abstract Background: We evaluated the association between metabolic syndrome (obesity plus two metabolic risk factors) and breast cancer outcomes according to molecular subtype. Methods: This population-based prospective cohort consisted of 3,267 women aged 20-69 diagnosed with a first primary invasive breast cancer from 2004-2015 in the Seattle–Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression: luminal (ER+), triple-negative (ER-/PR-/HER2-), and HER2-overexpressing (H2E) (ER-/HER2+). We used time-varying Cox models to assess the association between prevalent and incident metabolic syndrome and risks of recurrence, breast cancer-specific mortality, and all-cause mortality. Results: Metabolic syndrome was associated with a greater risk of recurrence (HR:3.24; 95% CI:1.13-9.33) and breast cancer-specific mortality (HR:5.34; 95% CI:2.32-12.31) only for the H2E subtype, and greater risks of all-cause mortality for luminal (HR:1.92; 95% CI:1.37-2.68), H2E (HR:5.09; 95% CI:2.51-10.32), and all cases combined (HR:1.90; 95% CI:1.42,2.53). We also observed heterogeneity in recurrence and mortality outcomes across specific components of metabolic syndrome and molecular subtypes. Conclusions: Metabolic syndrome is associated with all-cause mortality among women with breast cancer and with breast cancer-specific mortality among women with the H2E subtype. Impact: These results highlight the importance of managing comorbidities to decrease the risk for adverse outcomes among breast cancer survivors.