Real-world analysis of the association between new-onset depression and outcomes in metastatic breast cancer.

1117 Background: Depression is prevalent in patients with advanced cancers and it may influence the disease course and treatment. While depression is associated with worse survival in solid tumors, real-world data quantifying its impact on mortality and healthcare utilization patterns in metastatic breast cancer (MBC) are limited. We utilized a global de-identified database to evaluate the association of new-onset depression with overall survival (OS) and care utilization. Methods: We conducted a retrospective cohort study using the TriNetX global network. We identified adult women with MBC and survival greater than 6 months from diagnosis. Two cohorts were defined: (1) patients with first instance of depression 1-month to 3-years after MBC diagnosis, and (2) patients without depression before or during this period. Propensity score matching was performed (1:1) to balance baseline demographics, comorbidities, tumor receptor status, and previous cancer therapies. Outcomes included OS, palliative care utilization, ED visits, and Inpatient Hospitalizations over follow-up of 5 years. Results: We matched 2,753 patients per cohort with well-balanced baseline characteristics (mean age 60.1 ± 13.2 years). Depression was associated with shorter median OS (1,703 days vs not reached; HR 1.28, 95% CI 1.17–1.40, p<0.001) and 6.7% absolute increase in mortality risk (38.1% vs 31.4%). Patients with depression demonstrated significantly higher care utilization: with increased hospitalization (HR 1.52, CI 1.39–1.67), increased ED Visits (HR 1.41, 95% CI 1.30–1.52), and increased use of palliative care visits (HR 1.65, 95% CI 1.49–1.83). Subgroup analysis showed that those treated with common anti-depressants had lower median OS and higher care utilization, with a larger effect size and more statistical significance for SSRIs than SNRIs. Conclusions: In this large real-world cohort, new-onset depression in women with MBC was associated with significantly worse survival and increased emergency department, inpatient, and palliative care utilization. This finding may suggest a higher symptom burden or earlier recognition of complex needs. Exposure to common antidepressants was associated with lower OS and higher healthcare utilization, which may suggest residual confounding in the form of depression severity or MBC disease burden. Prospective studies are needed to further understand this relationship. These findings underscore the critical need for integrated psychosocial oncology screening.