EORTC QLQ-C30 symptom components and their functional correlates during adjuvant chemotherapy for early breast cancer: a multivariate analysis. Data from GEICAM/2003-02 study

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. 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. 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. 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. Cancer treatments often cause several symptoms at the same time, such as fatigue, pain, and sleep problems. These symptoms can affect how patients feel and how well they are able to carry out everyday activities. In this study, we analyzed data from women with early breast cancer receiving chemotherapy. We looked at how symptoms changed from before to after treatment and whether certain symptoms tended to worsen together. We also explored how these symptom patterns were linked to changes in physical, emotional, and social functioning, as well as overall quality of life. We found that many symptom changes followed one main pattern, which we describe as a general symptom burden. This pattern was driven mainly by fatigue, together with other common symptoms, and was strongly associated with worse functioning and poorer overall quality of life. These findings suggest that symptoms during chemotherapy should not be considered in isolation. Looking at overall symptom patterns may provide a more meaningful understanding of how treatment affects patients’ quality of life. However, these analyses should be viewed as exploratory approaches that complement, rather than replace, established questionnaire scoring methods and may help improve how treatment side effects are assessed and managed.