OBJECTIVE The goal of the study is to research on the factors affecting the quality of life (QoL) in breast cancer patients undergoing radiotherapy (RT). METHODS Four hundred and fifty-seven Stage I-III breast cancer patients undergoing adjuvant RT were evaluated using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTCBR23 questionnaires at four different times. RESULTS Over time, statistically significant differences were determined in parameters of QoL score as global health, physical, role, emotional, cognitive, and social functions (p<0.001) in the functional scale of module-C30; fatigue (p<0.001), appetite loss (p=0.012), insomnia (p=0.002), constipation (p=0.026), financial difficulty (p<0.001) in its symptom scale; future perspective (p=0.008), body image (p=0.001), sexual functioning (p=0.011) in module-BR23 functional scale; breast symptoms (p<0.001), systemic therapy side effects (p<0.001), arm symptoms (p=0.046), upset by hair loss (p=0.017) in its symptom scale. Menopausal status (physical and role functions, fatigue, and appetite loss), the type of breast surgery (physical, role and social functions, fatigue, and financial difficulties), the type of axillary interventions (global health status, social function, fatigue, and financial difficulties), adjuvant chemotherapy (financial difficulties, body image, systemic treatment side effects, arm symptoms, and hair loss), and lymphatic irradiation (global health status, role function, fatigue, systemic treatment side effects, and arm symptoms) have affected some scores of QoL. CONCLUSION The QoL scores for certain functions/symptoms were worse compared to the opposite cohort; that is, premenopausal versus postmenopausal, breast-conserving surgery versus modified radical mastectomy, sentinel lymph node biopsy versus axillary lymph node dissection, no adjuvant chemotherapy versus adjuvant chemotherapy, and no lymphatic irradiation versus lymphatic irradiation.