Abstract:Background and Aims Surgical treatment is a cornerstone of breast cancer management; however, the physical trauma and psychological burden associated with surgery may adversely affect patients' quality of life (QoL). Based on data from a prospective cohort, this study was conducted to evaluate changes in postoperative QoL among breast cancer patients and to identify mediating factors influencing QoL, thereby providing evidence for perioperative rehabilitation strategies.Methods Female breast cancer patients who underwent local surgical treatment at Suining Central Hospital between June 2024 and January 2025 were enrolled. The Constant-Murley Shoulder Score, EORTC QLQ-C30, and QLQ-BR23 questionnaires were used pre- and postoperatively to assess shoulder joint function, and QoL. Paired t-tests were used to analyze changes in scores before and after surgery. A mediation model was applied to explore the indirect pathways through which surgery impacts QoL. Additionally, subgroup analyses were conducted to compare QoL changes across different surgical modalities.Results A total of 148 patients were included, with median age of 54 (46-60) years old Postoperative psychological health significantly improved, while shoulder function and overall QoL scores markedly declined (all P<0.001). According to QLQ-C30, functional domains such as physical and role functioning worsened, while symptom burden increased. The QLQ-BR23 revealed significantly higher scores for breast and upper limb symptoms postoperatively (both P<0.001). Subgroup analyses showed that patients undergoing axillary lymph node dissection experienced greater declines in shoulder function and QoL compared to those receiving sentinel lymph node biopsy (both P<0.05). QoL deterioration was comparable between mastectomy and breast-conserving surgery, although the former was associated with more prominent pain and breast symptoms. Mediation analysis indicated that shoulder function, breast symptoms, and physical functioning served as mediators in the impact of surgery on QoL, while better psychological health exerted a protective effect.Conclusion Surgical treatment significantly affects postoperative QoL in breast cancer patients, with local functional impairment and symptom exacerbation serving as key mediators. Different surgical approaches have varying impacts on QoL. Enhancing postoperative shoulder rehabilitation, symptom management, and psychological support may improve patients' QoL.