Depressive symptoms are associated with poor prognosis and lower pathological complete response in triple-negative breast cancer: a single-center retrospective study

Background Depressive symptoms are common in patients with cancer, but their associations with survival and treatment response in triple-negative breast cancer (TNBC) remain uncertain. Methods This single-center retrospective study screened 19,335 patients with breast cancer treated during 2015–2025 and included 4,060 patients with TNBC. A single baseline Patient Health Questionnaire-9 (PHQ-9) assessment classified patients into normal/mild (score <10; n = 3,666) and moderate/severe (score ≥10; n = 394) symptom groups. Survival analyses included 3,878 patients without baseline distant metastasis; pathological complete response (pCR) analyses included 1,689 neoadjuvant chemotherapy (NACT) recipients with available response data. Cox and logistic regression models adjusted for recorded clinicopathological variables. An exploratory cross-sectional analysis of NHANES 2009–2018 was conducted separately. Results In the TNBC cohort, moderate/severe baseline depressive symptoms were associated with differences in T-stage and Ki-67 distributions and a higher frequency of baseline distant metastasis. N-stage distributions did not differ significantly (P = 0.059). Among patients without baseline distant metastasis, adjusted hazard ratios were 1.626 for overall survival (OS; 95% CI: 1.301–2.033; P < 0.001) and 1.439 for disease-free survival (DFS; 95% CI: 1.170–1.770; P < 0.001). The pCR rate was 26.34% in the moderate/severe group versus 36.18% in the normal/mild group (adjusted OR = 0.668; 95% CI: 0.474–0.930; P = 0.018). In NHANES, depressive symptoms were associated with higher odds of a self-reported history of any cancer (OR = 1.41; 95% CI: 1.19–1.67), whereas the breast cancer estimate was not statistically significant (OR = 1.43; 95% CI: 0.97–2.05). Conclusion Moderate/severe baseline depressive symptoms were associated with worse survival and lower pCR in this retrospective TNBC cohort. Reverse causation and unaccounted-for treatment delivery limit interpretation. These findings do not establish a causal effect or the prognostic utility of PHQ-9 beyond established factors. Prospective studies with repeated symptom assessments and detailed treatment records are needed.