Abstract
Purpose
Understanding how multiple symptoms jointly impact functioning is essential for interpreting patient-reported outcomes (PROs) in oncology. We aimed to characterize the main dimensions underlying change-from-baseline (CFB) in symptom scores during adjuvant chemotherapy for early breast cancer, and to examine their associations with functional outcomes.Patients and methods
We analyzed EORTC QLQ-C30 CFB scores from 820 patients enrolled in the GEICAM/2003-02 trial. Principal component analysis (PCA) was used to summarize correlated symptom changes into a smaller number of components, and graphical LASSO network modelling was applied to explore relationships among Health-Related Quality of Life (HRQoL) domains. Associations between components and functional scales and global health status were assessed using Spearman correlations.Results
Three components were identified in the pooled sample, explaining 53.6% of the variance: a dominant general symptom burden component, a gastrointestinal component, and a diarrhea-specific component. The general component, primarily defined by fatigue, pain, appetite loss, insomnia, nausea/vomiting and dyspnea, showed consistent negative correlations with all functional scales and global health status. Similar patterns were observed across treatment arms, although gastrointestinal-related components differed. Graphical LASSO identified fatigue as the symptom most strongly connected to functional impairment.Conclusion
Symptom changes during chemotherapy are not independent, but follow a multivariate structured pattern in which a general symptom burden, anchored by fatigue, plays a central role in functional decline. These findings suggest that multivariate approaches may provide a complementary exploratory framework for summarizing correlated patterns of treatment-related burden and generating hypotheses regarding PROs. Trial registration number ClinTrials.gov: GEICAM/2003-02: NCT00129389.