Partial Breast Re-irradiation in Women in Women with Locally Recurrent Breast Cancer Previously Treated with Conservative Surgery and Whole Breast Irradiation

Inclusion Criteria: 1. Isolated ipsilateral unifocal breast lesions; 2. Histologically confirmed invasive breast carcinoma or carcinoma in situ; 3. Limited size (\< 2 cm) without evidence of skin involvement; 4. Negative histologic margins of resection; 5. Negative axillary lymph nodes; 6. No synchronous distant metastases; 7. Bilateral breast mammogram or MRI within 120 days prior to study entry; 8. For invasive in-breast recurrence, no more than 120 days since whole-body (positron emission tomography) PET-CT scan OR CT scan of the chest, abdomen, and pelvis, and bone scan (if clinically relevant); 9. ≥ 24 months interval between initial breast conserving therapy (surgery and whole breast radiotherapy) and recurrence; 10. Female, aged \>18 years; 11. Life expectancy of greater than 12 months; 12. ECOG performance status \<2; 13. Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 4 months thereafter; 14. Participant is willing and able to give informed consent for participation in the study; Exclusion Criteria: 1. Regional recurrences (axillary, supraclavicular); 2. Positive histologic margins at resection; 3. Metastatic disease; 4. Previous breast RT performed with IORT, brachytherapy or previous partial breast treatment; 5. Known pathogenic mutation of BRCA1, BRCA2 or TP53 gene; 6. Patients who had chemotherapy within 2 weeks prior to study RT; 7. Participation in another clinical trial with any investigational agents within 30 days prior to study screening; 8. 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; 9. Significant comorbidity precluding RT for breast cancer (cardiovascular or pulmonary disease, sclerodermia, systemic lupus erythematosus); 10. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma of the skin and in situ carcinoma of the uterine cervix, endometrium or colon); 11. Inaccessibility for follow-up;