The goal of this interventional clinical trial is to evaluate if an individualized treatment strategy (involving radiation boost, surgery, and systemic consolidation) can improve progression-free survival in patients with breast cancer presenting with positive ipsilateral supraclavicular (ISLN) and/or internal mammary lymph nodes (IMLN).

The main questions it aims to answer are:

Is individualized hypofractionated radiotherapy with a local boost safe and effective when adjusted by the response to neoadjuvant treatment?

Does local surgery provide benefit for patients who have high residual tumor burden in these lymph nodes after neoadjuvant treatment?

How effective is intensified systemic therapy when tailored to the patient's molecular subtype?

Inclusion Criteria:

Female patients aged 18 to 75 years.

ECOG performance status ≤ 2.

Histologically confirmed invasive breast cancer.

Newly diagnosed breast cancer with pathologically confirmed positive ipsilateral supraclavicular lymph nodes (ISLN) and/or internal mammary lymph nodes (IMLN); for patients in whom IMLN biopsy is not feasible, clinically positive IMLN based on investigator assessment and imaging findings is acceptable.

Planned to receive neoadjuvant systemic therapy followed by breast-conserving surgery or mastectomy and axillary lymph node dissection, with or without supraclavicular and/or internal mammary lymph node dissection.

Adequate baseline organ function, defined as: absolute neutrophil count ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L; hemoglobin ≥ 9 g/dL (90 g/L); serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 60 mL/min; total bilirubin ≤ 1.5 × ULN; AST and/or ALT ≤ 2.5 × ULN; INR ≤ 1.5 and PT/APTT ≤ 1.5 × ULN.

Able and willing to comply with study procedures and scheduled follow-up.

Written informed consent obtained prior to any study-related procedures.

Exclusion Criteria:

Evidence of distant metastatic disease.

Presence of severe or uncontrolled concomitant diseases, including severe cardiac dysfunction; myocardial infarction, uncontrolled arrhythmia, or unstable angina within 3 months prior to enrollment; clinically significant pericardial disease; or severe pulmonary disease.

Prior radiotherapy to the chest wall or supraclavicular region.

Pregnancy, lactation, or any condition considered by the investigator to contraindicate radiotherapy.

History of or concurrent second primary malignancy, except for non-melanoma skin cancer, papillary or follicular thyroid carcinoma, carcinoma in situ of the cervix, contralateral non-invasive breast cancer, or other malignancies treated with curative intent with no evidence of disease for more than 3 years.