Ultra-hypofractionated Whole Breast Irradiation With Lumpectomy Cavity Boost for the Treatment of Stage I-III Breast Cancer

Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Age: ≥ 40 years * Female * Ability to read and understand English for questionnaires * Histologically confirmed breast cancer * Malignancy must be epithelial. Non-epithelial breast malignancies such as lymphoma or sarcoma are not allowed * Patients must have undergone breast conserving surgery. Re-excision for negative margins is allowed * Patients must have undergone surgical staging of the axilla (sentinel lymph node biopsy or axillary lymph node dissection) * Must have at least one-high risk feature that would necessitate a lumpectomy cavity boost by the treating radiation oncologist * Patient must have physician-reported "Excellent" or "Good" cosmesis post-lumpectomy and prior to radiation therapy based on the 4-point Global Cosmetic Score * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) Exclusion Criteria: * Prior radiation to the region of the involved breast that in the opinion of the investigator would preclude breast irradiation * Pathologically or clinically involved regional lymph nodes necessitating comprehensive regional nodal irradiation that includes the supraclavicular fossa * Clinically significant uncontrolled illness * Stage IV breast cancer * Diagnosis of Paget's disease of the nipple * Other prior or active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Pregnant or breastfeeding * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)