New research reveals that inflammatory responses may play a role in different types offatigueexperienced by many people withcancer. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society. Cancer-related fatigue can be a distressing and persistent burden that causes patients to feel physical, emotional, and/or cognitive tiredness or exhaustion. Activation of inflammatory responses by the tumor itself and/or by cancer treatment is thought to be a key biological driver of this symptom, but inflammatory activity across the cancer continuum has not been thoroughly examined. To investigate, researchers at the University of California, Los Angeles (UCLA) analyzed protein markers of inflammation in 192 women with early-stage breast cancer who were examined before radiation or chemotherapy and throughout the 18 months after treatment. At each assessment, women reported on different dimensions of fatigue (general, physical, mental, and emotional) and provided blood that was tested for protein markers of inflammation. These included two pro-inflammatory cytokines (TNF-α and IL-6) and two downstream markers of their activity (sTNF-RII and CRP). Higher levels of TNF-α, sTNF-RII, and IL-6 were linked with greater general fatigue, which involves feelings of tiredness and exhaustion. These effects remained even after accounting for age, race, education, body mass index, and cancer stage. Similarly, there was a positive association between physical fatigue, which involves feelings of physical weakness and heaviness, and TNF-α, sTNF-RII, and CRP. Conversely, higher levels of TNF-α and sTNF-RII were associated with lower levels of emotional fatigue. No significant associations between mental (or cognitive) fatigue and inflammatory markers were found. “Our findings indicate that inflammation plays a role in some aspects of cancer-related fatigue, but not others, and that these effects persist well after treatment,” said lead author Julienne E. Bower, PhD, of UCLA. “This is critical for developing targeted treatments for this common and disabling symptom.” Julienne E. Bower, Arielle Radin, Patricia A. Ganz, Michael R. Irwin, Steve W. Cole, Inflammation and dimensions of fatigue in women with early stage breast cancer: A longitudinal examination, Cancer, https://doi.org/10.1002/cncr.70038