title: The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer.
abstract: To examine relationships following adjuvant chemotherapy between circulating pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints in early stage breast cancer patients. 33 breast cancer patients who had completed initial treatment (surgery, ± radiation, 23 chemotherapy, 10 no chemotherapy) obtained resting (18)F-FDG PET/CT brain imaging at baseline and 1 year later. Pro-inflammatory cytokine markers (IL-1ra, sTNF-RII, CRP, and IL-6) and cognitive complaints were also assessed at both time points. At baseline, consistent correlations were seen between the left medial frontal and right inferior lateral anterior temporal cortices and inflammatory markers within the chemotherapy group, and not in the no chemotherapy group. After 1 year, correlations persisted in the medial frontal cortex and the temporal cortex, the latter shifting superiorly. Both of these regional correlations demonstrated the highest levels of significance when looking across the 1 year time frame (IL-1ra: peak voxel p < 0.0005; cluster size p < 0.0005, p = 0.001 after correction (medial prefrontal), p < 0.0005; cluster size p = 0.001, p = 0.029 corr. (anterior temporal), sTNF-RII: p < 0.0005; cluster size p = 0.001, p = 0.040 corr. (medial prefrontal)). Positive correlations were also seen within the chemotherapy group between baseline memory complaints and the medial frontal (p < 0.0005; cluster size p < 0.0005, p < 0.0005 corr.) and anterior temporal (p < 0.0005; cluster size p < 0.0005, p = 0.002 corr.) cortices at baseline and 1 year later. Metabolism in the medial prefrontal cortex and anterior temporal cortex was found to correlate with both memory complaints and cytokine marker levels in chemotherapy patients.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 200 Medical Plaza, Suite B114, Mail Code: 737024, Los Angeles, CA, 90095-7370, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Pomykala
authors.forename: P A
authors.initials: PA
authors.lastname: Ganz
authors.forename: J E
authors.initials: JE
authors.lastname: Bower
authors.forename: L
authors.initials: L
authors.lastname: Kwan
authors.forename: S A
authors.initials: SA
authors.lastname: Castellon
authors.forename: S
authors.initials: S
authors.lastname: Mallam
authors.forename: I
authors.initials: I
authors.lastname: Cheng
authors.forename: R
authors.initials: R
authors.lastname: Ahn
authors.forename: E C
authors.initials: EC
authors.lastname: Breen
authors.forename: M R
authors.initials: MR
authors.lastname: Irwin
authors.forename: D H S
authors.initials: DH
authors.lastname: Silverman
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008875:Middle Aged; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators