Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study Journal Article
| Authors: | Mandelblatt, J. S.; Small, B. J.; Zhou, X.; Nakamura, Z. M.; Cohen, H. J.; Ahles, T. A.; Ahn, J.; Bethea, T. N.; Extermann, M.; Graham, D.; Isaacs, C.; Jacobsen, P. B.; Jim, H. S. L.; McDonald, B. C.; Patel, S. K.; Rentscher, K. E.; Root, J. C.; Saykin, A. J.; Tometich, D. B.; Van Dyk, K.; Zhai, W.; Breen, E. C.; Carroll, J. E. |
| Article 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. © 2023 American Cancer Society. |
| Keywords: | cancer survival; controlled study; protein expression; aged; middle aged; systemic therapy; cancer staging; biomarkers; biological marker; animal; animals; breast cancer; interleukin 10; interleukin 8; inflammation; obesity; psychology; breast neoplasms; cancer survivor; tumor necrosis factor-alpha; breast tumor; comorbidity; interleukin 6; interleukin-6; cognition; cognitive defect; immunostimulation; hominid; ethnic group; genetic marker; tumor necrosis factor; interleukin-10; secondary analysis; cancer survivors; estrogen receptor positive breast cancer; executive function; immune activation; humans; human; female; article; hominidae; mediation analysis; processing speed; cancer-related cognitive decline; cognitive reserve; older survivors |
| Journal Title: | Cancer |
| Volume: | 129 |
| Issue: | 15 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-08-01 |
| Start Page: | 2409 |
| End Page: | 2421 |
| Language: | English |
| DOI: | 10.1002/cncr.34784 |
| PUBMED: | 37096888 |
| PROVIDER: | scopus |
| PMCID: | PMC10750797 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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