Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.
breast cancer
cancer-related cognitive decline
cognition
immune activation
inflammation
older survivors
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
revised:
08
02
2023
received:
15
10
2022
accepted:
03
03
2023
medline:
6
7
2023
pubmed:
25
4
2023
entrez:
25
04
2023
Statut:
ppublish
Résumé
Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates. Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.
Sections du résumé
BACKGROUND
Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls.
METHODS
Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects.
RESULTS
Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates.
CONCLUSIONS
Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.
Substances chimiques
Biomarkers
0
Interleukin-10
130068-27-8
Interleukin-6
0
Tumor Necrosis Factor-alpha
0
IL6 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2409-2421Subventions
Organisme : NCI NIH HHS
ID : K01 CA212056
Pays : United States
Organisme : NIA NIH HHS
ID : AG072976
Pays : United States
Organisme : NCI NIH HHS
ID : CA241337
Pays : United States
Organisme : NCI NIH HHS
ID : CA237535
Pays : United States
Organisme : NIA NIH HHS
ID : AG068086
Pays : United States
Organisme : NIA NIH HHS
ID : AG010133
Pays : United States
Organisme : NCI NIH HHS
ID : CA137788
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG065485
Pays : United States
Organisme : NCI NIH HHS
ID : CA270294
Pays : United States
Organisme : NCI NIH HHS
ID : CA261793
Pays : United States
Organisme : NCI NIH HHS
ID : CA008748
Pays : United States
Organisme : NIA NIH HHS
ID : AG028716
Pays : United States
Organisme : NCI NIH HHS
ID : CA244673
Pays : United States
Organisme : NIH HHS
ID : P30CA51008
Pays : United States
Organisme : NCI NIH HHS
ID : CA212056
Pays : United States
Organisme : NCI NIH HHS
ID : CA51008
Pays : United States
Organisme : NCI NIH HHS
ID : CA129769
Pays : United States
Organisme : NCI NIH HHS
ID : CA197289
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028716
Pays : United States
Organisme : NCI NIH HHS
ID : CA172119
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072976
Pays : United States
Informations de copyright
© 2023 American Cancer Society.
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