Evaluation of a Once Per Day Regimen of Accelerated Partial Breast Irradiation for Improved Breast Appearance in Patients with Low Risk, Hormone Responsive Breast Cancer

Inclusion Criteria

• Documented informed consent of the participant and/or legally authorized representative
• Age: >= 40 years
• Female
• Ability to read and understand English or Spanish for questionnaires
• Anatomic pathologic stage 0 (ductal carcinoma in situ [DCIS]) or stage IA (invasive) breast cancer
• Malignancy must be epithelial. Non-epithelial breast malignancies such as lymphoma or sarcoma are not allowed
• Patients must fall into one of these 3 groups: * Tissue from core biopsy or resection in patients with DCIS must show hormone sensitive receptors. Estrogen receptor (ER) positive (>= 60%) * Tissue from core biopsy or resection in patients with ER positive/ HER2 negative - invasive breast cancer must show hormone sensitive receptors as defined by: ** Oncotype DX ≤ 25 (if performed), OR ** Mammaprint Low (if performed), OR ** If Oncotype DX or Mammaprint are not performed, an Allred Score of 7 or 8. The following combination of proportion of ER positive cells and staining intensity are allowed: *** ER positive (34-66% of cells) and staining intensity is strong/3 positive (Allred 7) *** ER positive (≥ 67% of cells) and staining intensity is intermediate/2 positive (Allred 7) *** ER positive (≥ 67% of cells) and staining intensity is strong/3 positive (Allred 8) ** HER2+ breast cancer (any ER/PR status) as defined by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines based on local testing results
• Patients must have undergone breast conserving surgery with resulting negative surgical margins (no tumor on ink). Re-excision for negative margins is allowed. Patients with pathologically involved surgical margins are excluded
• Patients must have pathologic Tis or T1 disease
• Patients with HER2 positive disease must receive a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy
• Patients with ER positive/HER2 negative invasive breast cancer aged ≤ 70 years old, including patients with microinvasion, and patients of any age with HER2 positive disease must have undergone surgical staging of the axilla (sentinel lymph node biopsy or axillary lymph node dissection) and have pathologically confirmed uninvolved lymph nodes. All lymph nodes must be pathologically negative (pN0[i-]). pN0(i+), pN1mic, pN1-pN3 axillary lymph nodes are not allowed Although an axillary lymph node dissection is not anticipated for low-risk ER positive breast cancers, axillary lymph node dissection is permissible
• Patients >70 years old with ER positive/HER2 negative invasive breast cancer must have clinically node-negative disease (cN0). If the axilla in these patients is surgically staged, then these patients have to have pathologically confirmed uninvolved lymphy nodes. All lymph nodes must have be pathologically negative [pN0(i-)]. pN0(i+), pN1mic, pN1-3 axillary lymph nodes are not involved
• Patient must have self-reported “excellent” or “good” cosmesis post-lumpectomy and prior to radiation therapy based on the 4-point Global Cosmetic Score
• Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 1 month after the last dose of protocol therapy * Childbearing potential is defined as not being surgically sterilized; or have not been free from menses for > 1 year; or follicle stimulating hormone (FSH) and plasma estradiol not in the postmenopausal range. Any woman ≥ 60 years old is considered not of child bearing potential

Exclusion Criteria

• Any prior treatment with radiation therapy, chemotherapy or biologic therapy for the currently diagnosed breast cancer PRIOR to surgical resection
• Prior radiation to the region of the involved breast that in the opinion of the investigator would preclude partial breast irradiation
• Breast reduction surgery done in conjunction with surgical resection
• Clinically significant uncontrolled illness
• Diagnosis of Paget’s disease of the nipple
• Other prior or active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Pregnant or breastfeeding
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)