Contemporaneous and temporal symptom drivers during breast cancer chemotherapy: A prospective repeated-measures...

To statistically characterise both contemporaneous and temporal symptom networks to identify robust, stage-specific intervention targets.

We conducted a prospective cohort study of patients with stage I-III breast cancer who completed the MD Anderson Symptom Inventory across each of four chemotherapy cycles (T1-T4, April 2024 to June 2025). Exploratory factor analysis (EFA) first identified co-occurring symptom clusters, which informed the construction of cycle-specific cross-sectional networks via Gaussian graphical models and bridge centrality metrics. We then built cross-lagged panel networks to estimate directed symptom effects across successive cycles and applied non-parametric bootstrapping to derive confidence intervals and assess network stability.

A total of 153 patients completed data collection across four chemotherapy cycles. Parallel analysis showed three relatively stable symptom clusters across the first three chemotherapy cycles (T1-T3), but consolidation into two clusters occurred at the final cycle (T4). Cross-sectional hubs influencing contemporaneous symptom interplay were identified via bridge symptoms in cycle-specific cross-sectional networks: loss of appetite (T1), sadness (T2, T3), and numbness (T4). The core temporal drivers predicting future symptom cascades were identified via cross-lagged panel networks (CLPNs): shortness of breath (T1→T2), sadness (T2→T3), and somnolence (T3→T4). The precision of edge-weight yielded narrow to moderate 95 % confidence intervals (CI) for both cross-sectional and longitudinal networks. Case-drop bootstrapping (1000 iterations) demonstrated moderate to strong stability in the rank order of centrality indices.

Our integrative network approach reveals a dynamic, dual-mechanistic symptom framework (cross-sectional and temporal key symptom drivers): early intervention should target somatic symptoms, mid-treatment efforts should disrupt psychological amplifiers, and late cycles require attention to neurotoxic perpetuators. This phase-specific roadmap offers precision in symptom management for patients undergoing chemotherapy.