Impact of Exclusive Adjuvant Radiotherapy on Fatigue and Quality of Life in Breast Cancer: A Prospective Clinical Study

Background/Objectives: Breast cancer treatments, including adjuvant radiotherapy, significantly improve survival but are associated with cancer-related fatigue (CRF), a debilitating symptom that severely impacts quality of life. Previous studies often evaluate fatigue by combining radiotherapy with systemic therapies, confounding its independent association. This study aims to isolate the specific relation between exclusive radiotherapy and the longitudinal progression of fatigue in surgically treated breast cancer patients. Methods: A longitudinal study was conducted in a cohort of 70 women with breast cancer who underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Cancer-related fatigue levels were evaluated across behavioral, affective, sensory, and cognitive dimensions using the Piper Fatigue Scale-Revised (PFS-R), while global health status and quality of life (QoL) were measured using the EORTC QLQ-C30 questionnaire, both before and after radiotherapy. Data were analyzed using generalized linear mixed-effects models. Results: Following radiotherapy, a marked and statistically significant increase was observed in total fatigue (1.61 ± 1.16 vs. 5.37 ± 2.76; p < 0.001) and across all specific domains (p < 0.001), accompanied by a decline in global health status (82.6 ± 20.2 to 60.1 ± 29.2). Assessment time (pre- vs. post-RT) was identified as the factor most strongly associated with an increase in fatigue. However, better baseline global health status significantly attenuated the increase in total, behavioral, affective, and sensory fatigue (time × QoL interaction, p < 0.001). Furthermore, higher physical activity levels were significantly associated with lower behavioral fatigue (p = 0.042) and showed a protective trend for sensory (p = 0.055) and total fatigue (p = 0.092). Conclusions: Radiotherapy is strongly associated with a significant increase in cancer-related fatigue scores across all dimensions. Better baseline quality of life acts as a protective factor that is associated with attenuated fatigue progression, while regular physical activity correlates with a mitigated impact, particularly within the behavioral domain, although it did not reach statistical significance across all fatigue dimensions. These findings highlight the critical need for routine clinical monitoring of fatigue and strongly support the implementation of structured, exercise-based interventions during adjuvant treatment.