Risk models of cancer-related cognitive complaints among early breast cancer survivors in the CANTO cohort

BACKGROUND: Breast cancer (BC) survivors receiving adjuvant treatments often report clinically relevant cancer-related cognitive complaints (CRCC), which have a significant impact on quality of life. We aimed to develop a comprehensive model of prediction of CRCC, including clinical and serum inflammatory protein data. METHODS: We included 9575 stage I-III BC patients from the CANTO cohort (NCT01993498). Data were collected at diagnosis, 2 (year-2), and 4 (year-4) years post-diagnosis. Outcome of interest was CRCC (cognitive dimension of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 questionnaire, score < 75/100) at year-2 and year-4. Serum inflammatory markers (IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IFNg, IL-1, IL1Ra, TNF-a, and CRP) were available in a subset of patients with hormone-receptor-positive BC. Multivariable logistic regression models assessed associations of baseline clinical and inflammatory variables with CRCC. RESULTS: Rates of CRCC were 31% (diagnosis), 39% (year-2), and 37% (year-4). Baseline validated predictors of CRCC reported at year-2 were chemotherapy, pretreatment CRCC, pain, and fatigue; predictors of CRCC reported at year-4 were pretreatment CRCC, pain, and anxiety. Other clinically relevant factors associated with CRCC at both time points during model development were pretreatment insomnia, receipt of endocrine therapy, and younger age/premenopausal status. No significant associations were observed between inflammatory markers and CRCC. CONCLUSIONS: Approximately 1 in 3 BC survivors in this cohort reported CRCC at diagnosis, with this rate being stable until year-4 after diagnosis. Pretreatment symptom burden and chemotherapy were validated as risk factors for long-term CRCC. No associations between inflammatory markers and self-reported CRCC emerged from this study.