5 versus 9-Day Course of Whole Breast Radiation Therapy for the Treatment of Early-Stage Breast Cancer in Patients Who Have Undergo Lumpectomy, FAST NOVEMBER Trial

Inclusion Criteria

• Female participant aged ≥ 18 years * Participants > 50 years must have at least one of the following risk factors: ** Grade 3 invasive histology ** Estrogen receptor positivity less than 5% ** Lymphovascular invasion ** Margins < 2mm on surgical pathology ** Extensive intraductal component * Participants ≤ age 50 need no additional risk factors
• Histologically confirmed invasive carcinoma or ductal carcinoma in situ (DCIS) of the breast
• Breast cancer stage (American Joint Committee on Cancer [AJCC] version [v]8) 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
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, or Karnofsky performance status (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 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 Fraumeni, 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