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

Abstract

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.

Copyright © 2013 American Cancer Society.

Figures

Figure 1. Depression and fatigue before, during, and after radiation in breast cancer patients treated with or without chemotherapy

Prior chemotherapy-treated patients exhibited significantly higher depression and fatigue scores at all time points compared to non-chemotherapy-treated patients. IDS-SR-Inventory of Depressive Symptoms-Self Report; MFI-Multidimensional Fatigue Inventory. *p

Figure 2. NF-kB DNA binding and depression and fatigue before radiation in breast cancer patients treated with or without chemotherapy

Peripheral blood NF-kB DNA binding positively correlated with depression and fatigue in chemotherapy-treated (n=20) but not non-chemotherapy-treated (n=38) women (both p

Figure 3. Over-represented biological processes and NF-kB-mediated transcription factor pathways in differentially expressed genes in chemotherapy vs. non-chemotherapy-treated breast cancer patients before radiation

Chemotherapy was associated with an overrepresentation of immune and defense response genes and genes regulated by NF-kB family transcription factors.