The purpose of this trial is to investigate the toxicities and efficacy of super hypofractionated regional nodal radiotherapy (RNI) for one week in breast cancer patients treated with mastectomy or breast conserving surgery. Super hypofractionated radiotherapy will be delivered to chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). Eligible breast cancer patients will be followed for at least 5 years to evaluate the acute and late radiation-induced toxicities, locoregional recurrence, over survival, distant metastasis, and quality of life.

Eligible breast cancer patients will receive super hypofractionated radiotherapy of 5.2 Gy in 5 fractions within one week and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast. The dose is prescribed to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). All patients are treated with intensity modulated radiation therapy (IMRT) technique or intensity modulated proton therapy (IMPT). The primary endpoint is ≥2 grade any acute radiation induced toxicity event. Patients will be followed for at least 5 years to evaluate the acute and late radiation-induced toxicity, locoregional recurrence, over survival, distant metastasis, and quality of life.

Calculation of the required number of cases based on an alpha of 0.05 and a power of 80% with a maximal tolerable toxicity difference of 10% during and within 6 months after RNI comparing to conventional radiotherapy and lost rate of follow up of 10%. In total 197 patients are needed to be recruited.

Inclusion Criteria:

• Aged >18 years old
• Pathologically invasive breast cancer
• Undergoing BCS or mastectomy with reconstruction allowed, along with axillary lymph node dissection or sentinel lymph node biopsy.
• Axillary lymph node metastasis confirmed histologically (involving one or more nodes), or node-negative axilla with an indication for RNI as determined by the radiation oncologist.
• Karnofsky Performance Status scoring ≥80, and anticipative overall survival >5 years
• Surgery wound healed without infection
• Negative pathologically surgical margin
• Estrogen-receptor, Progesterone-receptor, HER-2, and Ki67 index assessment on the primary breast tumor or axillary nodes is feasible.
• Women of child-bearing potential must agree to use adequate contraception for up to 1 month before study treatment and the duration of study participation
• Ability to understand and willingness to participate the research and sign the consent forms

Exclusion Criteria:

• Pathologically positive ipsilateral supraclavicular lymph node
• Pathologically or radiologically confirmed involvement of ipsilateral internal mammary lymph nodes
• Pregnant or lactating women
• Severe non-neoplastic medical comorbidities that preclude radiation treatment (e.g., severe ischemic heart disease, arrhythmia, chronic obstructive pulmonary disease).
• History of non-breast malignancy within 5 years with the exception of lobular carcinoma in situ, basal cell carcinoma of the skin, carcinoma in situ of skin, Adenocarcinoma in situ of the lung and carcinoma in situ of the cervix
• simultaneous contralateral breast cancer or a prior history of ipsilateral breast cancer (including DCIS).
• Previous radiotherapy to the neck, chest and/or ipsilateral axillary region
• Active collagen vascular disease
• Definitive pathological or radiologic evidence of distant metastatic disease
• Primary T4 tumor