This study evaluates the impact of elective regional lymph node irradiation on N1 breast cancer patients receiving post-lumpectomy radiotherapy and anthracycline plus taxane (AT)-based chemotherapy. We randomly assign patients having one to three metastatic lymph nodes (pN1) after breast-conserving surgery (BCS) and AT-based chemotherapy to undergo either whole-breast and regional nodal irradiation (WB+RNI group) or whole-breast irradiation alone (WBI group).

Objective:

• Compare the effect of post-BCS WBI vs. WB+RNI on disease-free survival in pN1 breast cancer patients who received AT-based chemotherapy.
• Evaluate the impact of WBI or WB+RNI according to molecular subtype of tumor.
• Compare the treatment-related toxicities between the WBI and WB+RNI.
• Compare the patient's quality of life between the WBI and WB+RNI.

Outline: This is a a randomized, multi-center, phase III study. Patients are stratified according to molecular subtype of tumor (luminal A vs luminal vs luminal HER2 vs HER2-enriched vs basal-like), axillary lymph node management (sentinel lymph node biopsy [SLN] only vs axillary lymph node dissection+/- SLN) and participating institutions. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive WB+RNI.
• Arm II: Patients receive WBI alone.

Arm circumference and quality of life (EORTC QLQ-C30 & EORTC QLQ-BR23) are assessed within 2 weeks prior to randomization, during the last week of radiotherapy, at 3 months after completion of radiotherapy, and then annually thereafter for five years.

Patients are followed at 3 months after completion of radiotherapy and annually thereafter for seven years.

Inclusion Criteria:

• Histologically proven invasive carcinoma of the breast.
• One to three positive axillary lymph nodes (pN1) proven in pathologic specimen.
• Prior breast-conserving surgery and post-operative adjuvant chemotherapy including taxane.
• Administering adjuvant hormonal therapy in cases with hormone receptor-positive tumor.
• Administering anti-HER2 therapy in cases with HER2-positive tumor.

Exclusion Criteria:

• Metastases in supraclavicular or internal mammary lymph nodes.
• Metastases in distant organs.
• Neoadjuvant chemotherapy or hormone therapy before surgery.
• Not receiving adjuvant anthracycline and taxane.
• Bilateral breast cancer
• Previous history of radiotherapy of the ipsilateral breast or supraclavicular lymph nodes.
• Prior history of other types of cancer, except thyroid cancer, carcinoma in situ of the cervix, or skin cancer.