Long-term behavioral symptom clusters among survivors of early-stage breast cancer: Development and validation of a predictive model
Martina Pagliuca, Julie Havas, Emilie Thomas, Youenn Drouet, Davide Soldato, Maria Alice Franzoi, Joana Ribeiro, Camila Kelly Chiodi, E. Gillanders, Barbara Pistilli, Gwenn Menvielle, Florence Joly, Florence Lerebours, Olivier Rigal, Thierry Petit, Sylvie Giacchetti, Florence Dalenc, Johanna Wassermann, Olivier Arsène, Anne Laure Martin, Sibille Everhard, Olivier Trédan, Sandrine Boyault, Michelino De Laurentiis, Alain Viari, Jean‐François Deleuze, Aurélie Bertaut, Fabrice André, Inês Vaz-Luís, Antonio Di Meglio
Abstract
BACKGROUND: Fatigue, cognitive impairment, anxiety, depression, and sleep disturbance are cancer-related behavioral symptoms that may persist years after early-stage breast cancer, affecting quality of life. We aimed to generate a predictive model of long-term cancer-related behavioral symptoms clusters among breast cancer survivors 4 years after diagnosis. METHODS: Patients with early-stage breast cancer were included from the CANcer TOxicity trial (ClinicalTrials.gov identifier NCT01993498). Our outcome was the proportion of patients reporting cancer-related behavioral symptoms clusters 4 years after diagnosis (≥3 severe symptoms). Predictors, including clinical, behavioral, and treatment-related characteristics; Behavioral Symptoms Score (BSS; 1 point per severe cancer-related behavioral symptom at diagnosis); and a proinflammatory cytokine (interleukin 1b; interleukin 6; tumor necrosis factor α) genetic risk score were tested using multivariable logistic regression, implementing bootstrapped augmented backwards elimination. A 2-sided P less than .05 defined statistical significance. RESULTS: In the development cohort (n = 3555), 642 patients (19.1%) reported a cluster of cancer-related behavioral symptoms at diagnosis, and 755 (21.2%) did so 4 years after diagnosis. Younger age (adjusted odds ratio for 1-year decrement = 1.012, 95% confidence interval [CI] = 1.003 to 1.020), previous psychiatric disorders (adjusted odds ratio vs no = 1.27, 95% CI = 1.01 to 1.60), and BSS (adjusted odds ratio ranged from 2.17 [95% CI = 1.66 to 2.85] for BSS = 1 vs 0 to 12.3 [95% CI = 7.33 to 20.87] for BSS = 5 vs 0) were predictors of reporting a cluster of cancer-related behavioral symptoms (area under the curve = 0.73, 95% CI = 0.71 to 0.75). Genetic risk score was not predictive of these symptoms. Results were confirmed in the validation cohort (n = 1533). CONCLUSION: Younger patients with previous psychiatric disorders and higher baseline symptom burden have greater risk of long-term clusters of cancer-related behavioral symptoms. Our model might be implemented in clinical pathways to improve management and test the effectiveness of risk-mitigation interventions among breast cancer survivors.