Hypofractionated Regional Nodal Irradiation Clinical Trial for Women With Breast Cancer

Inclusion Criteria:

* Karnofsky performance status of 70-100%
* Histologic documentation of invasive adenocarcinoma of the breast
* One of the breast disease stages listed below:

  * Note: In the definitions below, definitive surgery is defined as the final surgery performed to obtain clear surgical margins
  * Neoadjuvant chemotherapy was not administered \*\* If neoadjuvant chemotherapy was NOT administered, pathologic staging must be T1-3, N1-2a following definitive surgery
  * Neoadjuvant chemotherapy was administered

    * If prior to initiation of neoadjuvant chemotherapy clinical staging was T1-3, N0, pathologic staging must be T1-3, N1-2a following definitive surgery
    * If prior to initiation of neoadjuvant chemotherapy clinical staging was T1-3, N1, pathologic staging must be T0-3, N0-2a following definitive surgery
    * If prior to initiation of neoadjuvant chemotherapy there was cytologic or pathologic confirmation of axillary nodal involvement (per any of the criteria listed below), pathologic staging must be T0-3, N0-2a following definitive surgery

      * Positive fine-needle aspiration (FNA) (ie, demonstrating malignant cells)
      * Positive core needle biopsy (ie, demonstrating invasive adenocarcinoma)
      * Positive sentinel lymph node biopsy (ie, demonstrating invasive adenocarcinoma)
* Complete resection of known breast disease by one of the following surgeries:

  * Lumpectomy with sentinel lymph node or axillary lymph node dissection
  * Mastectomy alone with sentinel lymph node or axillary lymph node dissection
  * Mastectomy plus reconstruction with sentinel lymph node or axillary lymph node dissection
* Margins of the resected specimen or re-excision specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the pathologist

  \* Notes: Additional operative procedures may be performed to obtain clear margins; focally positive margins are acceptable based on technical feasibility of additional surgery and/or the potential for benefit with further surgery based on the extent and location of the positive margin (eg, focally positive deep margin at the pectoralis fascia); also, patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection
* Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) testing performed on the primary breast tumor; when applicable, testing must have been performed prior to neoadjuvant chemotherapy
* Interval between the last surgery for breast cancer (including re-excision of margins) or the completion of adjuvant chemotherapy and study enrollment must be =\< 56 days (ie, a maximum of 8 weeks)

  \* Note: Radiotherapy must begin within 10 weeks following the last surgery for breast cancer or the last dose of adjuvant chemotherapy
* Recovery from surgery with the incision completely healed and no signs of infection
* If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may interfere with delivery of external beam radiation therapy (EBRT) should have resolved
* Women who are not postmenopausal or have not undergone hysterectomy must have a documented negative pregnancy test within 14 days prior to study registration

  \* Note: Postmenopausal is defined as one or more of the following:
  * Age \>= 60 years
  * Age \< 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range
  * Bilateral oophorectomy
* Women of child-bearing potential (WCBP) must agree to use a medically accepted form of pregnancy prevention for the duration of study treatment
* Ability to understand and willingness to sign the consent form written in English pregnancy test within 14 days prior to study registration

  \* Note: Postmenopausal is defined as one or more of the following:
  * Age \>= 60 years
  * Age \< 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range
  * Bilateral oophorectomy
* Women of child-bearing potential (WCBP) must agree to use a medically accepted form of pregnancy prevention for the duration of study treatment
* Ability to understand and willingness to sign the consent form written in English

Exclusion Criteria:

* Known definitive clinical or radiologic evidence of metastatic disease
* T4 tumors including inflammatory breast cancer
* Clinical nodal staging of N2 or N3 disease
* Pathologic nodal staging of N2b, N2c, or N3 disease
* Microscopic positive margins after definitive surgery

  \* Note: Patients with microscopically focally positive margins following lumpectomy or mastectomy are not excluded if re-excision is not technically feasible and/or there is no benefit to further surgery based on the extent and location of the positive margin
* Any history, not including the index cancer, of ipsilateral or contralateral invasive breast cancer or ipsilateral or contralateral DCIS treated with radiation therapy (RT)

  \* Note: Patients with synchronous or previous ipsilateral LCIS are eligible
* Any radiation therapy (RT) for the currently diagnosed breast cancer prior to study enrollment
* History of ipsilateral or contralateral breast or thoracic RT for any condition
* History of ipsilateral or contralateral axillary surgery for any condition
* History of lymphedema involving the ipsilateral or contralateral arm at present or at any time in the past
* Synchronous contralateral breast cancer requiring RT
* Overall geometry (eg, breast size if intact breast) precludes the ability to achieve dosimetric requirements

  \* Note: Set-up devices for breast positioning are permitted
* Unresolved post-surgical complications (eg, significant infection) with healing difficulties
* Active collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
* Pregnancy or breastfeeding
* Diagnosis or treatment for a non-breast malignancy within 5 years of study registration, with the following exceptions: complete resection of basal cell carcinoma or squamous cell carcinoma of the skin and any in situ malignancy after curative therapy
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements