This study will evaluate the local control, complication rates, cosmetic results, and quality of life between patients treated with a single fraction vs. five fractions of accelerated partial breast irradiation (S_APBI vs. F_APBI) when used as the sole method of radiation therapy.

Inclusion Criteria:

• AJCC 7th Edition stage 0 or I (TisN0 ≤ 2 cm or T1N0) histologically confirmed carcinoma of the breast, treated with partial mastectomy. Axillary sampling is required only for cases of invasive cancers. Tumor size is determined by the pathologist. Clinical size may be used if the pathologic size is indeterminate. Patients with invasive cancer must have no positive axillary lymph nodes with at least 6 axillary lymph nodes as assessed by axillary ultrasound, axillary sampling, or axillary sentinel node procedure.
• Negative histologic margins of partial mastectomy or re-excision specimen. The posterior margin is always considered widely negative if the partial mastectomy extended to the pectoralis fascia and there is no tumor on ink. Margins generally are positive if there is invasive or noninvasive tumor at the inked resection margin, close but negative if the tumor is within 2 mm of the inked margin and negative if the tumor is at least 2 mm away from the inked edge.[42]
• Invasive ductal, lobular, medullary, papillary, colloid (mucinous), tubular histologies, or mixed histologies (lesions ≤ 2 cm) that are estrogen and/or progesterone receptor positive and do not exhibit HER2/neu gene amplification OR ductal carcinoma in situ (lesions ≤ 2 cm) that are estrogen and/or progesterone receptor positive.
• Neoadjuvant hormone therapy, chemotherapy, or biologic therapy is not allowed prior to APBI, but adjuvant hormone therapy may have been started after surgery. Planned chemotherapy or biologic therapy must not start for at least 4 weeks after the completion of APBI.
• Good candidate for treatment per protocol in the judgment of the PI and/or treating physician following simulation.
• Postmenopausal status.
• Age ≥ 50 years at diagnosis.
• Able to understand and willing to sign IRB-approved written informed consent document.
• All radiation therapy must be planned for delivery at BJH or a BJH/Siteman satellite location with the following stipulations: F_APBI may be delivered at any Siteman location. S_APBI treatment must occur at the main Siteman location at BJH and will be delivered on a Viewray Unit, the Varian Edge unit, or the Varian Halcyon unit. Pre and post treatment care is allowed at any Siteman center.

Exclusion Criteria:

• Presence of distant metastases.
• Nonepithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (tumors in different quadrants of the breast, or tumors separated by at least 4 cm) with other clinically or radiographically suspicious areas in the ipsilateral breast unless confirmed to be negative for malignancy by biopsy.
• Histologically confirmed positive axillary nodes in the ipsilateral axilla. Palpable or radiographically suspicious contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Prior non-hormonal therapy for the present breast cancer, including radiation therapy or chemotherapy.
• Diagnosis of systemic lupus erythematosis, scleroderma, or dermatomyositis.
• Diagnosis of a coexisting medical condition which limits life expectancy to < 2 years.
• Paget's disease of the nipple.
• Skin involvement, regardless of tumor size.
• Unsatisfactory breast for APBI as determined by the treating physician. For example, if there is little breast tissue remaining between the skin and pectoralis muscle after surgery, treatment with APBI is technically problematic.
• Partial mastectomy so extensive that the cosmetic result is fair or poor prior to APBI as determined by the treating physician.
• Surgical margins which cannot be microscopically assessed or are positive at pathological evaluation.
• Time between final definitive breast surgical procedures to APBI simulation is greater than 8 weeks.