Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors

  • S. K
  • M. J
  • D. K
 et al. 
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Abstract

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 (TNFalpha) 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 TNFalpha and lower levels of IL-6 with a significant interaction between these two cytokines suggesting a potential modulatory effect of IL-6 on TNFalpha. 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 TNFalpha and IL-6. © 2012 .

Author-supplied keywords

  • *brain size
  • *breast cancer
  • *breast cancer/dt [Drug Therapy]
  • *cancer survivor
  • *chemotherapy
  • *hippocampal volume
  • *hippocampus
  • *human
  • *interleukin 6
  • *interleukin 6/ec [Endogenous Compound]
  • *memory
  • *nuclear magnetic resonance imaging
  • *tumor necrosis factor alpha XT - breast cancer /
  • *tumor necrosis factor alpha/ec [Endogenous Compou
  • *verbal memory
  • adult
  • aged
  • amnesia
  • article
  • breast cancer/dt [Drug Therapy]
  • cancer chemotherapy
  • cancer survivor
  • clinical article
  • cognitive defect
  • controlled study
  • cross-sectional study
  • cyclophosphamide/dt [Drug Therapy]
  • cytokine
  • disease association
  • doxorubicin/dt [Drug Therapy]
  • female
  • fluorouracil/dt [Drug Therapy]
  • human
  • inflammation
  • methotrexate/dt [Drug Therapy]
  • nuclear magnetic resonance
  • nuclear magnetic resonance imaging
  • paclitaxel/dt [Drug Therapy]
  • patient
  • priority journal
  • protein protein interaction
  • serum
  • survivor
  • therapy

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Authors

  • Kesler S.

  • Janelsins M.

  • Koovakkattu D.

  • Palesh O.

  • Mustian K.

  • Morrow G.

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