Elizabeth K Belcher1, Eva Culakova1, Nikesha J Gilmore1, Sara J Hardy1,2, Amber S Kleckner1, Ian R Kleckner1, Lianlian Lei3, Charles Heckler1, Michael B Sohn4, Bryan D Thompson1, Louis T Lotta1, Zachary A Werner1, Jodi Geer5, Judith O Hopkins6, Steven W Corso7, David Q Rich8, Edwin van Wijngaarden8, Michelle C Janelsins1. 1. Department of Surgery, Supportive Care in Cancer Division, University of Rochester Medical Center, Rochester, NY, USA. 2. Department of Radiation Oncology and Neurology, University of Rochester Medical Center, Rochester, NY, USA. 3. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. 4. Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA. 5. Metro Minnesota Community Oncology Research Consortium, Louis Park, MN, USA. 6. Novant Health Cancer Institute, Kernersville, NC, USA. 7. Upstate Carolina National Cancer Institute Community Oncology Research Program, Spartanburg Regional Medical Center, Spartanburg, SC, USA. 8. Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA.
Abstract
BACKGROUND: Inflammation may contribute to cognitive difficulties in patients with breast cancer. We tested 2 hypotheses: inflammation is elevated in patients with breast cancer vs noncancer control participants and inflammation in patients is associated with worse attention and processing speed over the course of chemotherapy. METHODS: Serum cytokines (interleukin [IL]-4, 6, 8, 10; tumor necrosis factor [TNF]-α) and soluble receptors [sTNFRI, II]) were measured in 519 females with breast cancer before and after chemotherapy and 338 females without cancer serving as control participants. Attention and processing speed were measured by Rapid Visual Processing (RVP), Backward Counting (BCT), and Trail Making-A (TMT-A) tests. Linear regression models examined patient vs control cytokines and receptor levels, adjusting for covariates. Linear regression models also examined relationships between patient cytokines and receptor levels and test performance, adjusting for age, body mass index, anxiety, depression, cognitive reserve, and chemotherapy duration. Statistical tests were 2-sided (α = .05). RESULTS: sTNFRI and sTNFRII increased over time in patients relative to controls, whereas IL-4, IL-6, and IL-10 decreased. Prechemotherapy, higher IL-8 associated with worse BCT (β = 0.610, SE = 0.241, P = .01); higher IL-4 (β = -1.098, SE = 0.516, P = .03) and IL-10 (β = -0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (β = 0.841, SE = 0.260, P = .001), sTNFRI (β = 6.638, SE = 2.208, P = .003), and sTNFRII (β = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (β = -1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (β = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (β = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (β = -0.564, SE = 0.253, P = .03). CONCLUSIONS: Generally, worse attention and processing speed were associated with higher inflammatory cytokines and receptors and lower anti-inflammatory cytokines in patients; future confirmatory studies are needed.
BACKGROUND: Inflammation may contribute to cognitive difficulties in patients with breast cancer. We tested 2 hypotheses: inflammation is elevated in patients with breast cancer vs noncancer control participants and inflammation in patients is associated with worse attention and processing speed over the course of chemotherapy. METHODS: Serum cytokines (interleukin [IL]-4, 6, 8, 10; tumor necrosis factor [TNF]-α) and soluble receptors [sTNFRI, II]) were measured in 519 females with breast cancer before and after chemotherapy and 338 females without cancer serving as control participants. Attention and processing speed were measured by Rapid Visual Processing (RVP), Backward Counting (BCT), and Trail Making-A (TMT-A) tests. Linear regression models examined patient vs control cytokines and receptor levels, adjusting for covariates. Linear regression models also examined relationships between patient cytokines and receptor levels and test performance, adjusting for age, body mass index, anxiety, depression, cognitive reserve, and chemotherapy duration. Statistical tests were 2-sided (α = .05). RESULTS: sTNFRI and sTNFRII increased over time in patients relative to controls, whereas IL-4, IL-6, and IL-10 decreased. Prechemotherapy, higher IL-8 associated with worse BCT (β = 0.610, SE = 0.241, P = .01); higher IL-4 (β = -1.098, SE = 0.516, P = .03) and IL-10 (β = -0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (β = 0.841, SE = 0.260, P = .001), sTNFRI (β = 6.638, SE = 2.208, P = .003), and sTNFRII (β = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (β = -1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (β = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (β = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (β = -0.564, SE = 0.253, P = .03). CONCLUSIONS: Generally, worse attention and processing speed were associated with higher inflammatory cytokines and receptors and lower anti-inflammatory cytokines in patients; future confirmatory studies are needed.
Authors: Sunita K Patel; Andrew L Wong; F Lennie Wong; Elizabeth Crabb Breen; Arti Hurria; Mackenzie Smith; Christine Kinjo; I Benjamin Paz; Laura Kruper; George Somlo; Joanne E Mortimer; Melanie R Palomares; Michael R Irwin; Smita Bhatia Journal: J Natl Cancer Inst Date: 2015-06-22 Impact factor: 13.506
Authors: Jeanne S Mandelblatt; Tim A Ahles; James C Root; Xingtao Zhou; Jaeil Ahn; Brent J Small; Wanting Zhai; Traci Bethea; Judith E Carroll; Harvey Jay Cohen; Asma Dilawari; Martine Extermann; Deena Graham; Claudine Isaacs; Paul B Jacobsen; Heather Jim; Brenna C McDonald; Zev M Nakamura; Sunita K Patel; Kelly Rentscher; Andrew J Saykin; Kathleen Van Dyk Journal: Breast Cancer Res Treat Date: 2022-05-19 Impact factor: 4.624