Ultra-Hypofractionated vs Moderate Hypofractionated Radiotherapy for Regional Lymph Nodes in High Risk Breast Cancer

Inclusion Criteria:

1. Provide a signed and dated informed consent form (ICF) before the initiation of any trial-specific procedures.
2. Age ≥ 18 years.
3. Histologically confirmed invasive breast cancer.
4. Have received breast-conserving surgery or mastectomy with axillary staging, including sentinel lymph node biopsy, targeted axillary dissection and/or axillary lymph node dissection.
5. Tumor stage is classified as T1, T2, or T3, as defined by the AJCC Cancer Staging Manual, 8th Edition.
6. Meeting at least one of the following conditions:

   1. Pathological nodal status of pN2 or pN3a;
   2. Pathological nodal status of pN1 with one or more of the following high-risk factors:

   (I), Age \< 40 years. (II), Tumor location in the central or inner quadrant. (III), Estrogen Receptor (ER) negative. (IV), Presence of lymphovascular invasion (LVI). (V), Histological grade III. (VI), Patients presenting with clinical stage cN2-3a before neoadjuvant treatment.
7. Pathologically negative surgical margins, defined as "no ink on tumor."
8. Karnofsky Performance Status (KPS) score ≥ 80.
9. Documented biomarker status for Estrogen Receptor (ER), Progesterone Receptor (PR), HER2, and Ki-67.
10. Sufficient wound healing from surgery, with no signs of active infection at the intended radiation site.

Exclusion Criteria:

1. Nodal stage is classified as N3b or N3c, as defined by the AJCC Cancer Staging Manual, 8th Edition.
2. Has undergone or is planning immediate breast reconstruction with a permanent implant or tissue expander.
3. Evidence of distant metastatic disease.
4. Diagnosis of synchronous bilateral invasive breast cancer or a history of prior invasive cancer in either breast.
5. History of prior radiation therapy to the chest, axillary, or supraclavicular regions.
6. Known active collagen vascular diseases, particularly systemic lupus erythematosus or scleroderma, which are contraindications to radiotherapy.
7. Presence of any severe, uncontrolled co-morbidity or medical condition that, in the investigator's judgment, would render the participant unsuitable for the study, compromise protocol compliance, or confound the interpretation of study results.
8. History of any other malignancy within the 5 years before enrollment, with the exception of adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix.
9. Participants who are pregnant or lactating at the time of study enrollment. (Note: In accordance with the standards of each participating institution, women of childbearing age are required to undergo pregnancy testing within 2 weeks prior to randomization.)