Abstract
BACKGROUND: Establishing whether women with major depressive disorder who develop breast cancer have poor outcomes is key to optimizing care for this population. To this end, we examined associations between major depressive disorder and breast cancer recurrence and mortality. METHODS: Using medical record data from the US Department of Veterans Affairs health-care system, we established a retrospective cohort of women with local or regional stage invasive breast cancer between 2010 and 2019 and followed them through 2022. We used a 2-year window to identify women diagnosed with major depressive disorder before breast cancer diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between major depressive disorder and breast cancer recurrence and mortality while accounting for competing risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. RESULTS: We identified 6051 women with breast cancer, of whom 1754 (29%) had major depressive disorder. The mean (SD) age at breast cancer diagnosis was 57 (11) years. In multivariable analyses, women with major depressive disorder had a 37% (hazard ratio = 1.37, 95% CI = 1.19 to 1.57) higher risk of recurrence and a 30% (hazard ratio = 1.30, 95% CI = 1.02 to 1.64) higher risk of breast cancer mortality. The association between major depressive disorder and recurrence was stronger among women with estrogen receptor-positive breast cancer. In secondary analyses, there were statistically significant interactions between major depressive disorder and multiple exposures with respect to recurrence, including current smoking, substance abuse, and nonreceipt of screening mammography. CONCLUSIONS: Women with major depressive disorder had inferior breast cancer outcomes compared with women without a history of major depressive disorder. Research is needed to investigate underlying mechanisms linking depression to breast cancer progression and evaluate interventions to improve outcomes in this high-risk population.