Changes in S100 calcium-binding protein β (S100β) and cognitive function from pre- to post-chemotherapy among women with breast cancer

Aaron N Huynh; AnnaLynn M Williams; Elizabeth K Belcher; Paige Van Haute; Louis T Lotta; Bryan Thompson; Colleen Netherby-Winslow; Amarinthia Curtis; Benjamin T Esparaz; Carla Jorgensen; Sara Alberti; Emma Bentley; Hongying Sun; Eva Culakova; Michelle C Janelsins

doi:10.1016/j.bbih.2024.100860

Changes in S100 calcium-binding protein β (S100β) and cognitive function from pre- to post-chemotherapy among women with breast cancer

Brain Behav Immun Health. 2024 Sep 8:41:100860. doi: 10.1016/j.bbih.2024.100860. eCollection 2024 Nov.

Authors

Aaron N Huynh^{1

2}, AnnaLynn M Williams^{1

3}, Elizabeth K Belcher¹, Paige Van Haute¹, Louis T Lotta¹, Bryan Thompson¹, Colleen Netherby-Winslow¹, Amarinthia Curtis⁴, Benjamin T Esparaz⁵, Carla Jorgensen⁶, Sara Alberti¹, Emma Bentley¹, Hongying Sun¹, Eva Culakova¹, Michelle C Janelsins^{1

2

3}

Affiliations

¹ University of Rochester Medical Center, Department of Surgery, Division of Supportive Care in Cancer, Rochester, NY, 14642, USA.
² University of Rochester Medical Center, Department of Neuroscience, Rochester, NY, 14642, USA.
³ Wilmot Cancer Institute, Rochester, NY, 14642, USA.
⁴ Upstate Carolina Consortium Community Oncology Research Program, Spartanburg Regional Medical Center, Spartanburg, SC, 29303, USA.
⁵ Heartland Cancer Research NCORP, Decatur, IL, 62526, USA.
⁶ NCORP of the Carolinas - Prism Health NCORP/Greenville, Greenville, SC, 29605, USA.

Abstract

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (r_s), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (r_s = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (r_s = -0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Keywords: Blood-brain barrier integrity; Breast cancer; Cancer; Cancer-related cognitive decline; Chemotherapy; Cognition; Cognitive decline; S100; S100β.