{"doi":"10.1002/cncr.34784","title":"Plasma levels of interleukin‐6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study","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.","journal":"Cancer","year":2023,"id":337189,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337738,"name":"Brent J. 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Bethea","orcid":"0000-0003-3205-2078","position":7,"is_corresponding":false},{"id":595843,"name":"Martine Extermann","orcid":"0000-0003-4381-1199","position":8,"is_corresponding":false},{"id":402363,"name":"Deena Graham","orcid":"0000-0003-1111-6984","position":9,"is_corresponding":false},{"id":242394,"name":"Claudine Isaacs","orcid":"0000-0002-9646-1260","position":10,"is_corresponding":false},{"id":337741,"name":"Paul B. Jacobsen","orcid":"0000-0002-4427-8800","position":11,"is_corresponding":false},{"id":337736,"name":"Heather Jim","orcid":"0000-0001-7353-3711","position":12,"is_corresponding":false},{"id":260693,"name":"Brenna C. McDonald","orcid":"0000-0001-6895-4490","position":13,"is_corresponding":false},{"id":426788,"name":"Sunita K. Patel","orcid":"0000-0002-9023-8391","position":14,"is_corresponding":false},{"id":641923,"name":"Kelly E. Rentscher","orcid":"0000-0003-1887-3953","position":15,"is_corresponding":false},{"id":402364,"name":"James C. Root","orcid":"0000-0001-7332-6165","position":16,"is_corresponding":false},{"id":27595,"name":"Andrew J. Saykin","orcid":"0000-0002-1376-8532","position":17,"is_corresponding":false},{"id":356060,"name":"Danielle B. Tometich","orcid":"0000-0002-5939-0635","position":18,"is_corresponding":false},{"id":435686,"name":"Kathleen Van Dyk","orcid":"0000-0003-1500-930X","position":19,"is_corresponding":false},{"id":403482,"name":"Wanting Zhai","orcid":null,"position":20,"is_corresponding":false},{"id":337739,"name":"Elizabeth C. Breen","orcid":"0000-0001-6046-4999","position":21,"is_corresponding":false},{"id":298119,"name":"Judith Carroll","orcid":"0000-0001-5516-0819","position":22,"is_corresponding":false},{"id":292842,"name":"Jeanne S. Mandelblatt","orcid":"0000-0002-2490-005X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:10:26.690308Z","pmid":"37096888","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}