Abstract Background Randomized controlled trials in Western population have demonstrated hypofractionated radiotherapy to be a safe and effective option as compared to radiation doses of 45- 50Gy in 25 fractions at 1.8-2 Gy/fraction for breast cancer patients. However, most of the patients in such studies had early stage, good prognostic disease and the efficacy and safety in patients with higher stage disease is debated. In Indian centres, patients typically present at younger age with symptomatic or locally advanced disease. Protracted treatment times remain a significant hurdle for many patients who have to travel to distant places for treatment. This retrospective analysis assesses the outcome of patients with stage I-III breast cancers who were treated with hypofractionated regimen (40Gy/15 fractions over 3 weeks with 2.67Gy/fraction each day) following either conservative surgery or mastectomy with or without regional nodal irradiation. Materials and Methods: Patients with stage I-III Breast cancers treated at Regional Cancer Centre, Thiruvananthapuram, India during 1st Jan 2013 to 31st Dec 2015 were identified from the Hospital Based Cancer Registry. Among a total of 3577 patients, 642 (18%) were found to have received adjuvant hypofractionated radiotherapy and were included in this analysis. The study was approved by the Institutional Review Board. The mean age was 50.2 years (range 20 - 78 years). There were 4 males. The clinical stages were I, II and III for 5.9%, 38% and 33.4% patients; stage was not known for 22.4% who underwent excision of the breast lump prior to reporting. The molecular subtypes were hormone receptor (HR) +, HER-2 - (46.1%), HR+, HER + (10.6%), HR-, HER2 + (13.6%) and Triple Negative (26%), unknown (2.8%). Majority (62.5%) underwent primary surgery while the remaining received neoadjuvant systemic therapy prior to surgery. Sixty-eight percent patients underwent modified radical mastectomy (MRM) and 32% underwent breast conservation. Chemotherapy was received by 95% patients and all HR+ patients received endocrine therapy. Only 55.5% of the HER 2+ patients received anti-HER2 therapy. Overall Survival (OS), and Disease Free Survival (DFS) were assessed using Kaplan Meier analyses for the entire cohort and according to stage, lymphovascular emboli (LVE), grade, molecular subtypes and type of surgery. Multivariable Cox regression analysis was performed to assess for prognostic factors. Results All 642 patients were included in this analysis. At a median follow up of 53 months, 122 (19.0%) patients had relapsed. The first site of recurrence was loco-regional alone for 6 (4.9%) patients. Among the 112 (91.8%) patients who failed at distant sites, 16 had loco-regional disease as well. Four (3.3%) patients recurred with contralateral breast cancer. The median time to recurrence was 26 months. The 4-year DFS and OS were 81.5% and 88.8% for the entire cohort. Patients with higher clinical and pathological stage, LVE, triple negative biology and those who had undergone MRM had poorer outcome. Pathological stage was the only independent prognostic factor for both OS and DFS. Radiotherapy was well tolerated; grade of skin toxicity was 0, 1, 2and 3 for 56.2%, 39%, 4.3% and 0.5% patients respectively. Conclusion The results of this study appear to confirm the efficacy and safety of the use of hypofractionated radiotherapy in Stage I-III breast cancers. Loco-regional recurrences were quite low and DFS and OS do not seem to be compromised in spite of higher disease stage and younger population. Keywords: Breast cancer, radiotherapy, hypofractionation Citation Format: Anand Sebastian, Preethi Sara George, J V Ammu, K R Rajeev, Beela Sarah Mathew. Curative hypofractionated radiotherapy for stage I-III breast cancer patients- Experience from a tertiary cancer centre in South India [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-22.