Abstract This study evaluated whether lymphedema, patient-reported arm and shoulder morbidity and quality of life one year after axillary surgery are affected by stage or axillary surgery type between early stage patients and patients with locally advanced breast cancer who underwent surgery following neoadjuvant therapy. By determining the risk factors associated with severe lymphedema and deterioration of patient-reported outcomes, lymphedema could be prevented by early intervention to improve the prognosis of lymphedema and quality of life. Material and Methods: Between January 2021 and May 2022, a total of 253 breast cancer patients, 128 early stage and 125 locally advanced stage who underwent surgery including sentinel lymph node biopsy (SLNB) with/without axillary lymph node dissection (ALND) following neoadjuvant therapy were included in this study. The patients who underwent upfront surgery were defined as early-stage, and those who underwent surgery following neoadjuvant chemotherapy were considered as having locally advanced breast cancer (LABC) who have also participated in the prospective MF18-03 registry trial. Patients were prospectively evaluated by the SF-12 quality of life and QUICK-DASH hand, arm, and shoulder range of motion questionnaires and circumferential tape measurements of the arm width to evaluate the lymphedema before surgery, and 6 month- and 12-month assessments. The volume difference of 10% or more in the operated arm compared to the healthy arm was considered as lymphedema. Results: In the assessment of SF-12 quality of life questionnaire, there was a decrease in physical function scores at the 6th month despite recovery at the 12th month in both groups compared to the initial preoperative scores (p< 0,001). Moreover, patients with locally advanced breast cancer were found to have decreased SF-12 general health (p=0.024), vitality (p=0.034), and mental health scores in one year after surgery (p=0.004). Patients with mastectomy and locally advanced breast cancer were more likely to have a diminished arm and shoulder function as assessed with the QUICK-DASH questionnaire at the 6th and 12th months compared to those with breast conservation (6. month, p=0,009, 12. month, p=0.004), and early breast cancer, respectively (6. month, p=0.014, 12. month, p< 0.001) In the present cohort, lymphedema was detected in 19 (7.5%) patients including 16 cases with mild (11-20%), 2 cases with moderate (21-40%), and one case with severe (41-80%) lymphedema one year after surgery. Axillary dissection was found to be associated with an increased risk of lymphedema (SLNB, 5.0% vs ALND, 17.6%; p=0.005). Similarly, removal of >6 lymph nodes was also associated with an increased risk of lymphedema that was not statistically significant (<6 LNs, 6.4% vs >6LNs, 10.8%; p=0.277). Among those with LABC, however, patients with removal >6 LNs were more likely to have lymphedema (>6 LNs, 15.4% vs <6 LNs, 5.8%; p=0.096). Conclusion: These findings suggest that only an extensive axillary surgery was associated with an increased risk of breast cancer-related lymphedema. Patients with a mastectomy were more likely to have diminished arm and shoulder function compared to those with breast conservation. Furthermore, patients with locally advanced breast cancer were more likely to have a dispaired quality of life score and a limited arm and shoulder function regardless of the presence of lymphedema. Early prompt diagnosis and therapy of lymphedema can therefore potentially improve quality of life. Citation Format: Halime Gul Kilic, Selman Emiroglu, Ekin Ozgorgu, Mustafa Tukenmez, Atilla Bozdogan, Mahmut Muslumanoglu, Vahit Ozmen, Dilsad Sindel, Abdullah Igci, Aydan Oral, Neslihan Cabıoğlu. PATIENT REPORTED OUTCOMES IN TERMS OF ARM AND SHOULDER FUNCTIONS AND QUALITY OF LIFE AND LYMPHEDEMA ARE AFFECTED BY THE STAGE, AND EXTENT OF AXILLARY SURGERY IN THE EARLY POSTOPERATIVE PERIOD OF PATIENTS WITH BREAST CANCER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-03.