Inclusion Criteria:

* Histologically confirmed invasive carcinoma of the breast of any of the following histologies (ductal, lobular, mammary, medullary, or tubular); patients with metaplastic breast cancer are not eligible
* Patients will be staged according to the TNM staging system

* For patients not receiving neoadjuvant chemotherapy, pathologic staging must be T0N1-2a, T1N1-2a, T2N1-2a, T3N0-2a, and all M0 status
* For patients receiving neoadjuvant chemotherapy, clinical pre-chemo staging and post mastectomy pathological staging is required for all patients; patients who have received neoadjuvant chemotherapy and are pathologically cT0-2 and N0 are only eligible if biopsy-proven clinically N1 or N2 disease is documented prior to the start of neoadjuvant chemotherapy; cT3N0 patients or ypT3N0 patients who receive neoadjuvant chemotherapy may be eligible based on clinical or pathological T stage, and do not require pathologically positive lymph nodes
* Note: Higher of the clinical or pathological T and N stage are used for final staging, if receiving neoadjuvant chemotherapy; all patients with clinical, radiographic or pathological T4, N3 or involved internal mammary disease (N1b, N1c, and N2b) are not eligible. N1mic patients are eligible.
* No prior therapeutic radiation therapy to the chest, neck or axilla; prior radioactive oral iodine is permitted
* No prior history of ipsilateral breast cancer (invasive disease or ductal breast carcinoma in situ \[DCIS\]); lobular carcinoma in situ (LCIS) and benign breast disease is allowed
* No history of prior or concurrent contralateral invasive breast cancer; benign breast disease, LCIS or DCIS of contralateral breast is allowed
* No active collagen vascular diseases, such as: systemic lupus erythematous, scleroderma, or dermatomyositis
* Negative inked histologic margins from mastectomy pathology (no invasive cells at margin). Patients with DCIS at margin are eligible.
* No significant post mastectomy complications in the ipsilateral breast requiring an unplanned re-operation or admission for intravenous (IV) antibiotics; re-operation for margins evaluation, nodal completion and routine reconstruction is acceptable
* Radiation oncologist intends to treat all target volumes and respect all normal tissues in accordance with the dosimetric constraints described (simulation before registration recommended)
* Radiation oncologist is planning to treat regional lymph nodes including internal mammary nodes and meet acceptable protocol dosimetric requirements
* Radiation oncologist is NOT planning to utilize a chest wall/scar boost
* Patient must have undergone immediate reconstruction at the time of mastectomy or be planning to undergo reconstruction within 18 months after radiation
* Treating physician and patient must plan to start radiation treatment within the timeframes specified in protocol.
* If a tissue expander is utilized it needs to be a fluid filled expander, NO air expander (unless completely deflated) during radiation therapy
* For patients with diabetes, hemoglobin A1C test must have been performed =< 90 days prior to registration
* No co-existing medical conditions with life expectancy < 5 years
* No other malignancy within 5 years of registration with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix
* Negative pregnancy test (serum or urine HCG) in women of child-bearing potential ≤ 7 days prior to registration. Patients who have received a bilateral tubal ligation still require a negative pregnancy test for eligibility. A female of childbearing potential is a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 12 consecutive months
* Women of child-bearing potential must agree to utilize a form of birth control or agree to undergo sexual abstinence during radiation therapy
* Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
* Patients must be able to read and comprehend English, in order to be able to complete study questionnaires; however, patients participating through Canadian Cancer Trials Group (CCTG) institutions who can read and comprehend French are eligible