Shelli Kesler, Michelle Janelsins, Della Koovakkattu, Oxana Palesh, Karen Mustian, Gary Morrow, Firdaus S. Dhabhar

Many survivors of breast cancer show significant cognitive impairments, including memory deficits. Inflammation induced by chemotherapy may contribute to hippocampal changes that underlie these deficits. In this cross-sectional study, we measured bilateral hippocampal volumes from high-resolution magnetic resonance images in 42 chemotherapy-treated breast cancer survivors and 35 healthy female controls. Patients with breast cancer were, on average, 4.8 ± 3.4 years off-therapy. In a subset of these participants (20 breast cancer, 23 controls), we quantified serum cytokine levels. Left hippocampal volumes and memory performance were significantly reduced and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα) concentrations were significantly elevated in the breast cancer group compared to controls. In the breast cancer group, lower left hippocampal volume was associated with higher levels of TNFα and lower levels of IL-6 with a significant interaction between these two cytokines suggesting a potential modulatory effect of IL-6 on TNFα. Verbal memory performance was associated with cytokine levels and left hippocampal volume in both groups. These findings provide evidence of altered hippocampal volume and verbal memory difficulties following breast cancer chemotherapy that may be mediated by TNFα and IL-6.