The primary objective of this study is to document lymphedema rates in patients requiring regional nodal irradiation (RNI) who receive hypofractionated radiation as compared to conventional radiation.

Participants with stage II or stage III node-positive breast cancer, or T3N0 node-negative will receive hypofractionated radiation for 4 weeks. We hypothesize that patients receiving a shorter course of radiation will have reduced lymphedema. Lymphedema is diagnosed when the patient's arm circumference measures 10% or more as compared to pre-treatment (baseline) arm circumference measurement. Secondary endpoints will address the effectiveness, quality of life, and side effect profile of a shortened course of treatment.

Inclusion Criteria:

• Karnofsky Performance Status 50% - 100%
• Diagnosis of stage II or III node-positive breast cancer (NOTE: Stages include: T4a-cNany, T3N1, TxN2.) OR T3N0 node-negative breast cancer.
• For patients with TxN1 disease, one of the following criteria must be met: Grade 3; ≤ 45 years of age at time of screening for this study; extensive Lymphovascular Space Invasion (LVSI); 3 lymph nodes positive; hormone-negative disease; positive lymph nodes after chemotherapy; or extracapsular extension
• Prior surgery and chemotherapy allowed, no prior radiation to the target area (breast or chest and nodes). NOTE: Radiation should occur 3-12 weeks after last chemotherapy or surgery, whichever comes last.
• Women of child-bearing potential (WOCP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

Exclusion Criteria:

• Diagnosis of inflammatory breast cancer
• Previously diagnosed malignancy excluding basal or squamous cell carcinoma of the skin (unless disease-free for 5 years or more)
• Diagnosis of scleroderma
• Diagnosis of lupus
• Diagnosis of active dermatomyositis
• Diagnosis of metastatic disease
• Pregnant or nursing