Characterizing modifiable risk factors of breast cancer recurrence and mortality in a cohort of women with luminal, triple-negative, and HER2-overexpressing breast cancer

Breast cancer is the most common cancer diagnosed among women in the United States; ten to 20% of survivors will experience a recurrence in the decade after diagnosis. To improve the understanding of the relationship between modifiable risk factors and breast cancer recurrence and mortality, overall and by subtype, we evaluated the relationship between smoking, alcohol, metabolic syndrome, and breast cancer outcomes according to molecular subtype. This population-based prospective cohort included women aged 20-69 diagnosed with a first primary invasive breast cancer from 2004 through 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 (TN) (ER-/PR-/HER2-), and HER2-overexpressing (H2E) (ER-/HER2+). First, we fit Cox proportional hazards models to assess the association between alcohol consumption and smoking status at diagnosis and risks of breast cancer outcomes. Second, we used time-varying Cox models to assess the association between metabolic syndrome and risks of breast cancer outcomes. Breast cancer patients with a history of smoking at diagnosis had elevated risks of adverse outcomes underscoring the need to prioritize smoking cessation among women diagnosed with breast cancer. We found no clear association between current alcohol use overall at diagnosis and breast cancer recurrence or mortality; however, we did observe a decreased risk of breast cancer recurrence and mortality among TN cases who currently consumed four or more drinks per week at diagnosis. We also found metabolic syndrome to be associated with all-cause mortality among women with breast cancer and with breast cancer recurrence and mortality among women with H2E breast cancer.