Metabolic Syndrome and Risks of Breast Cancer Outcomes for Luminal, Triple-Negative, and HER2-Overexpressing Subtypes.

Background: We evaluated the association between metabolic syndrome (MetS; 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 ages 20 to 69 years diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor, and HER2 expression: luminal (ER+), triple-negative (ER-/progesterone receptor negative/HER2-), and HER2-overexpressing (H2E; ER-/HER2+) subtypes. We used time-varying Cox models to assess the association of prevalent and incident MetS with risks of recurrence, breast cancer-specific mortality (BCSM), and all-cause mortality (ACM).

Results: MetS was associated with a greater risk of recurrence [HR, 3.24; 95% confidence interval (CI), 1.13-9.33] and BCSM (HR, 5.34; 95% CI, 2.32-12.31) only for the H2E subtype and greater risks of ACM 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 MetS and molecular subtypes.

Conclusions: MetS is associated with ACM among women with breast cancer and with BCSM 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.