Predictors of depression in breast cancer patients treated with radiation: Role of prior chemotherapy and nuclear factor kappa B

BACKGROUND Depression is common during and after breast cancer treatment. However, the role of specific therapeutic modalities and related biologic mechanisms remains unclear. Radiation is an essential component of breast-conserving therapy and may contribute to depression in patients with breast cancer through the activation of inflammatory pathways. METHODS Depressive symptoms and inflammatory mediators, including nuclear factor kappa B (NF-κB), were assessed at baseline (before radiation), during radiation, and 6 weeks after radiation in 64 women who had stage 0 through IIIA breast cancer. RESULTS No significant increases in depressive symptoms occurred during or after radiation, although a number of patients exhibited moderate-to-severe depression throughout the study. Multivariate analyses of baseline factors predictive of depression revealed that educational status, perceived stress, prior chemotherapy, and peripheral blood NF-κB DNA binding all were independent predictors of persistent depressive symptoms after radiation (all P <.05). Of these factors, only prior chemotherapy was associated with inflammatory mediators, including NF-κB DNA binding, soluble tumor necrosis factor-alpha receptor 2, and interleukin-6, which, in univariate analyses predicted depressive symptoms after radiation (all P <.05). Chemotherapy-treated patients also exhibited an over-representation of gene transcripts regulated by NF-κB. CONCLUSIONS Radiation was not associated with increased depressive symptoms in the current study, but of disease and treatment-related factors, prior chemotherapy predicted significant depression after radiation. Longitudinal studies are warranted to investigate the relationship among prior chemotherapy, inflammation, and persistent depression after breast cancer treatment.