Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery

PRIMARY OBJECTIVES:

I. To determine the pathologic complete response (pCR) rate after hypofractionated
radiotherapy to the whole breast alone, based on the postsurgical specimen.

SECONDARY OBJECTIVES:

I. To evaluate acute and late toxicity with preoperative radiation including grade >= 2
pneumonitis.

II. To estimate the 5-year locoregional control, distant recurrence, invasive disease-free
survival, cause-specific survival, and overall survival.

CORRELATIVE AND EXPLORATORY OBJECTIVES:

I. To evaluate patient-reported outcomes. II. To evaluate clinical features, treatment
technique, dose-volume parameters, histologic and genetic variants associated with adverse
events, and fair and poor cosmetic outcomes or unplanned surgical intervention.

III. Evaluate tumor mutation signatures before and after radiation; correlate tumor mutation
signatures before and after radiation with pathologic information at the time of surgery.

IV. To describe the pathologic changes seen in breast cancer patients with preoperative
radiation.

OUTLINE:

Participants undergo hypofractionated radiation therapy daily for 5 days, then undergo
standard of care surgery 4-16 weeks after radiation therapy.

After completion of study treatment, participants are followed up at 12 weeks, 6, 12, 24, and
36 months, and 5 years after radiation therapy.

Inclusion Criteria:

- Histological confirmation of breast cancer

- Clinical stage T0-T2 N0 M0

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2

- Able to and provides Institutional Review Board (IRB) approved study specific written
informed consent

- Study entry must be within 120 days of last biopsy (breast)

- Able to complete all mandatory tests

- Willing to return to enrolling institution for follow-up (during the active monitoring
phase of the study)

- Planned breast surgery and indications for whole breast radiotherapy

Exclusion Criteria:

- Medical contraindication to receipt of radiotherapy

- Severe active co-morbid systemic illnesses or other severe concurrent disease which,
in the judgment of the investigator, would make the patient inappropriate for entry
into this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements or providing informed consent

- Active systemic lupus or scleroderma

- Pregnancy

- Women of childbearing potential who are unwilling to employ adequate contraception

- Prior receipt of ipsilateral breast or chest wall radiation

- Recurrent breast cancer

- Indications for comprehensive regional nodal irradiation

- No neo-adjuvant therapy