1. A bio-behavioral model of systemic inflammation at breast cancer diagnosis and fatigue of clinical importance 2 years later.
- Author
-
Di Meglio, A., Havas, J., Pagliuca, M., Franzoi, M.A., Soldato, D., Chiodi, C.K., Gillanders, E., Dubuisson, F., Camara-Clayette, V., Pistilli, B., Ribeiro, J., Joly, F., Cottu, P.H., Tredan, O., Bertaut, A., Ganz, P.A., Bower, J., Partridge, A.H., Martin, A.L., and Everhard, S.
- Subjects
- *
EPIDERMAL growth factor receptors , *RECEIVER operating characteristic curves , *HEALTH behavior , *CANCER fatigue , *CANCER diagnosis , *HORMONE receptor positive breast cancer - Abstract
We aimed to generate a model of cancer-related fatigue (CRF) of clinical importance 2 years after diagnosis of breast cancer building on clinical and behavioral factors and integrating pre-treatment markers of systemic inflammation. Women with stage I-III hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer were included from the multimodal, prospective CANTO cohort (NCT01993498). The primary outcome was global CRF of clinical importance [European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 ≥40/100] 2 years after diagnosis (year 2). Secondary outcomes included physical, emotional, and cognitive CRF (EORTC QLQ-FA12). All pre-treatment candidate variables were assessed at diagnosis, including inflammatory markers [interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon γ, IL-1 receptor antagonist, tumor necrosis factor-α, and C-reactive protein], and were tested in multivariable logistic regression models implementing multiple imputation and validation by 100-fold bootstrap resampling. Among 1208 patients, 415 (34.4%) reported global CRF of clinical importance at year 2. High pre-treatment levels of IL-6 (quartile 4 versus 1) were associated with global CRF at year 2 [adjusted odds ratio (aOR): 2.06 (95% confidence interval [CI] 1.40-3.03); P = 0.0002; area under the receiver operating characteristic curve = 0.74]. Patients with high pre-treatment IL-6 had unhealthier behaviors, including being frequently either overweight or obese [62.4%; mean body mass index 28.0 (standard deviation 6.3 kg/m2)] and physically inactive (53.5% did not meet World Health Organization recommendations). Clinical and behavioral associations with CRF at year 2 included pre-treatment CRF [aOR versus no pre-treatment CRF: 3.99 (95% CI 2.81-5.66)], younger age [aOR per 1-year decrement: 1.02 (95% CI 1.01-1.03)], current tobacco smoking [aOR versus never: 1.81 (95% CI 1.26-2.58)], and worse insomnia or pain [aOR per 10-unit increment: 1.08 (95% CI 1.04-1.13), and 1.12 (95% CI 1.04-1.21), respectively]. Secondary analyses indicated additional associations of IL-2 [aOR per log-unit increment: 1.32 (95% CI 1.03-1.70)] and IL-10 [0.73 (95% CI 0.57-0.93)] with global CRF and of C-reactive protein [1.42 (95% CI 1.13-1.78)] with cognitive CRF at year 2. Emotional distress was consistently associated with physical, emotional, and cognitive CRF. This study proposes a bio-behavioral framework linking pre-treatment systemic inflammation with CRF of clinical importance 2 years later among a large prospective sample of survivors of breast cancer. • 34.4% of 1208 stage I-III breast cancer survivors had cancer-related fatigue of clinical importance 2 years after diagnosis. • High pre-treatment levels of the pro-inflammatory cytokine IL-6 were associated with global fatigue 2 years later. • Individuals with high levels of IL-6 had higher BMI and were less physically active than those with lower levels. • Higher pre-treatment IL-2 and IL-10 were also associated with higher and lower likelihood of global fatigue, respectively. • Higher C-reactive protein was associated with higher likelihood of cognitive fatigue. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF