Internal Mammary Node Irradiation After Neoadjuvant Systemic Therapy for Breast Cancer

This multicenter randomized controlled trial evaluates whether internal mammary node irradiation (IMNI) improves oncologic outcomes in patients with breast cancer who have residual pathologically positive lymph nodes after neoadjuvant systemic therapy. Eligible participants will be randomly assigned in a 1:1 ratio to receive locoregional radiotherapy either with or without irradiation of the internal mammary lymph nodes. The primary outcome is disease-free survival. Secondary outcomes include overall survival, breast cancer mortality, locoregional recurrence-free survival, distant metastasis-free survival, and treatment-related toxicity, particularly cardiac and pulmonary toxicity. A total of 1,760 participants are planned to be enrolled across multiple centers in Thailand.

Inclusion Criteria: * Histologically confirmed breast cancer with pathologically proven lymph node positivity after neoadjuvant systemic therapy. * Received neoadjuvant chemotherapy and/or targeted therapy and/or immunotherapy before surgery. * Underwent either breast-conserving surgery or mastectomy with lymph node evaluation and is planned to receive adjuvant locoregional radiotherapy. * Planned treatment with three-dimensional conformal radiotherapy (3D-CRT) or a more advanced radiotherapy technique. * Female ≥ 18 years Exclusion Criteria: * Clinical or radiologic evidence of internal mammary lymph node involvement of any size. * Inflammatory breast cancer. * Bilateral breast cancer. * Multiple primary malignancies, except basal cell carcinoma and premalignant gynecologic lesions including CIN, HSIL, LSIL, VIN, and VAIN. * Prior chest irradiation. * Disease progression before radiotherapy. * Metastatic disease (M1) according to the AJCC 8th edition.