Trial Comparing 3 Schedules of Hypofractionated Whole Breast Irradiation in Females With Early Stage Breast Cancer

1. Radiotherapy Timing If the patient is not receiving chemotherapy, WBI is to be initiated within 9 weeks following lumpectomy or re-excision of margins. For patients receiving chemotherapy, WBI is to begin no fewer than 2 weeks and no more than 8 weeks after the last cycle of chemotherapy. 2. Randomization: 138 patients will be randomized using permuted blocks randomization to 3 equal comparable arms. \- Dose Prescriptions Arm 1: One week WBI: 27Gy/5 fractions /1 week. 5.4 Gy/fraction ± boost to tumor bed 5.4 Gy/ 1 fraction, 2 days after the end of WBI. Arm 2: Once weekly WBI: 28.5 Gy/ 5 fractions/ 5 weeks. 5.7 Gy/fraction ± boost to tumor bed 5.7 Gy/ 1 fraction, one week after the end of WBI. WBI is given on the same day each week. Arm 3: Hypofractionated WBI 40 Gy/ 15 fractions/ 3 weeks. 2.67 Gy/ fraction ± boost to tumor bed 10 Gy/ 4 fraction / 4 days after the end of WBI. 3-Tumor bed boost A tumor bed boost is recommended to high-risk patients \[Age \< 50 years, high grade\] according to the National Comprehensive Cancer Network (NCCN) guidelines. 4-Radiotherapy simulation, Localization and Outlining: * The guidelines for contouring will conform to the policies set by the Radiation Therapy Oncology Group (RTOG) Breast cancer Atlas. www.rtog.org/CoreLab/ContouringAtlases/BreastCancerAtlas.aspx * Megavoltage ( MV) photon beams with energies ≥ 6 MV are required. * Radiotherapy Planning: Computed tomography based conformal radiotherapy (CT-based 3D-CRT) planning with tissue inhomogeneity correction is required . 5- Systemic Therapy * Chemotherapy Adjuvant chemotherapy may be given at the discretion of the patient's medical oncologist. The use of chemotherapeutic agents during radiation therapy is not allowed. The use of neoadjuvant chemotherapy is not allowed. * Hormonal therapy Patients with ER-positive and/or PR-positive tumors should be treated with hormonal therapy for a minimum of 5 years. The use of hormonal therapy during radiation therapy is allowed. * Trastuzumab Trastuzumab is given to HER2 positive patients. The use of Trastuzumab during radiation therapy is allowed. 6-Surgical Treatment: * All patients will undergo CBS, axillary staging and/or dissection with negative surgical margins (sm). * Negative surgical margin (Curigliano, 2017) * Invasive breast cancer: no ink on tumor * DCIS: 2mm * Surgical clips will be used to define the tumor bed borders * Breast reconstruction and cosmetic breast implants are not allowed 7-Follow-up. Schedule of Follow up: * History and physical exam for all randomized patients will occur every 3 months in the first 2 years after the date of end of radiotherapy treatment * Monitor and refer for lymphedema management. * Mammography will be requested annually