The goal of this study is to evaluate 5 days vs. 9 days of whole breast radiation.

Inclusion Criteria:

• Female participant aged ≥ 18 years.

  --Participants must have at least one of the following risk factors:

  • Grade 3 invasive histology
  • Estrogen receptor positivity less than 5%
  • Lymphovascular invasion
  • Invasive margins <2mm on surgical pathology
  • DCIS final positive margin
  • Extensive intraductal component
  • Age ≤ 50 years
  • Tumor size > 2 cm

• Histologically confirmed invasive carcinoma or Ductal Carcinoma In Situ (DCIS) of the breast.

• Breast cancer stage (AJCC v8) T0-3, N0, M0. T0 N0 is allowed if whole breast radiation is recommended by the treating physician.

• Lumpectomy within 84 days of the start of radiation.

• ECOG Performance Status ≤ 2, or KPS ≥ 50

• Negative inked histologic margins from lumpectomy, with the exception of a focus of positive margin at the pectoralis fascia.

• Negative pregnancy test for participants of childbearing potential, evidence of permanent surgical sterilization, or post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  • < 50 years of age:

    • Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
    • Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution

  • ≥ 50 years of age:

    • Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
    • Had radiation-induced menopause with last menses >1 year ago; or
    • Had chemotherapy-induced menopause with last menses >1 year ago

• Sexually active participants of childbearing potential must agree to use highly effective method of contraception (defined in Section 5.4.1) during the course of radiation and for 30 days after radiation.

• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

• Bilateral breast cancer.

• Prior radiation therapy to the chest.

• Prior chemotherapy.

• Recurrent disease.

• Known metastases or node positive.

• Major chest surgery which is expected to impact study participation 8 weeks prior to starting study drug.

• Prior breast malignancy in either breast.

• The diagnosis of any other malignancy which, in the opinion of the Investigator, is likely to negatively impact the subject's safety or ability to participate in the study.

• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:

  • Cardiovascular disorders:

    • Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
    • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before the first dose.

  • Any other condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow, social/ psychological issues, etc.)

• Significant post lumpectomy complications requiring an unplanned re-operation for surgical complications or admission for IV antibiotics. Re-operation for margins evaluation or nodal evaluation is acceptable. Draining of a seroma is not considered a complication unless it has become infected.

• Breast neuroendocrine carcinoma or sarcoma histology.

• Radiation sensitizing disease or condition (e.g. connective tissue disease, li fremani, etc.).

• Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.

• Participants receiving concurrent radiation sensitizing medications or therapies.

Female participant aged ≥ 18 years

Study will have no masking as the treating investigator and patient will need to know their radiation schedule for accurate treatment planning.