Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study

Background Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Methods Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. Results We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Conclusions Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.