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ABSTRACT: 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.
SUBMITTER: Mandelblatt JS
PROVIDER: S-EPMC10750797 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Mandelblatt Jeanne S JS Small Brent J BJ Zhou Xingtao X Nakamura Zev M ZM Cohen Harvey J HJ Ahles Tim A TA Ahn Jaeil J Bethea Traci N TN Extermann Martine M Graham Deena D Isaacs Claudine C Jacobsen Paul B PB Jim Heather S L HSL McDonald Brenna C BC Patel Sunita K SK Rentscher Kelly E KE Root James C JC Saykin Andrew J AJ Tometich Danielle B DB Van Dyk Kathleen K Zhai Wanting W Breen Elizabeth C EC Carroll Judith E JE
Cancer 20230425 15
<h4>Background</h4>Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls.<h4>Methods</h4>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 a ...[more]