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

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Abstract
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.
Funding Information
  • National Cancer Institute (T32CA009168)
  • National Cancer Institute (P30 CA015704)
  • National Cancer Institute (261201000029C)
  • U.S. Department of War (BC112721)

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