Ultrahypofractionated Whole Breast Radiation Following Chemotherapy

Inclusion Criteria:

1. Patients aged at least 60 years with invasive BC (T1-3) with clinically or pathologically negative axillary nodes following BCS who have a high-risk Mammaprint or Oncotype testing and receive chemotherapy. (If no axillary surgery planned, patients must have pre-operative negative axillary ultrasound)
2. Invasive ductal, lobular, medullary, papillary, colloid (mucinous), or tubular histologies are allowed
3. Any receptor status is allowed (ER/PR/Her2-neu)
4. Patients with negative resection margins defined as 2 mm from ink, or a negative re-excision
5. Bilateral BC is allowed, provided each cancer meets inclusion criteria
6. Nodal RT is not allowed
7. There must be no concern for distant metastatic disease
8. Neoadjuvant or adjuvant chemotherapy is permitted provided pretreatment clinical and radiographic staging meets inclusion criteria. Specific adjuvant/neoadjuvant therapies are at the discretion of the treating Medical Oncologist. There are no systemic therapies that are not allowed on this study.
9. Patients must be deemed fit to receive the prescribed systemic therapy
10. Immunotherapy is allowed
11. Targeted Her-2 neu therapy, including concurrent therapy is allowed
12. Other targeted therapies are allowed (including but not limited to CDK inhibitors)
13. Endocrine therapy, including concurrent therapy is allowed
14. Participation in other non-RT clinical trial is allowed
15. Must be able to sign informed consent

Exclusion Criteria:

1. Patients with stage IV BC
2. Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re-excision, the patient is eligible)
3. Prior thoracic or breast RT
4. The following RT methods and techniques are not permitted:

   * Brachytherapy or intraoperative RT (IORT)
   * Proton therapy
   * Regional nodal RT
   * Tumor bed boost
5. Patients who have breast reconstruction with implant or expander
6. Patients who have had a mastectomy for current BC
7. Patients requiring a tumor bed boost
8. Palpable or radiographic suspicious or contralateral lymph nodes or N2 disease
9. Paget's disease of the nipple.
10. Non-epithelial breast malignancies such as sarcoma or lymphoma
11. History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry
12. Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma
13. Pregnancy or lactation at the time of study entry/ or intention to become pregnant during treatment.
14. Patients with serious medical illness or psychiatric illness that would interfere with the trial.
15. Patients with active infection in the radiation treatment portal.