Level I-II Axillary Irradiation in Breast Cancer With Sentinel-Node Macro-metastases

PRIMARY OBJIECTIVE:

To evaluate whether level I-II axillary irradiation is non-inferior to whole regional nodal irradiation in terms of disease-free survival in clinically node-negative breast cancer patients with 1-2 sentinel lymph node macro-metastases.

SECONDARY OBJECTIVES:

I. to estimate the difference of overall survival; II. to estimate the difference of ipsilateral regional recurrence; III. to estimate the difference of ipsilateral local regional recurrence; IV. to estimate the difference of distant recurrence; V. to estimate the difference of radiation related toxicities and quality of life.

Outline: Patients are randomized in a 1:1 ratio to two treatment arms.

Arm A (Level I-II axillary irradiation): Radiation is delivered to the breast after breast conserving surgery(BCS) or chest wall after mastectomy, level I-II axillary lymph nodes. Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.

Arm B (Entire regional nodal irradiation): Radiation is delivered to the breast after BCS or chest wall after mastectomy, whole axillary lymph nodes (levels I-III) and supraclavicular lymph nodes. IMN is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.

Inclusion criteria

• Female ≥ 18 years of age;
• Newly diagnosed primary invasive breast cancer;
• Clinically stage T1-3N0M0;
• Patients received surgery as first treatment,and have undergone breast conserving-surgery or mastectomy (with or without breast reconstruction) with negative margins;
• Have one or two macrometastases (>2 mm) at sentinel lymph node biopsy,and without further axillary lymph node dissection;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• Will receive endocrine therapy for at least 5 years for estrogen receptor (ER) and/or progesterone receptor (PR) positive patients; will receive anti-HER2 (human epidermal growth factor receptor 2) therapy for 1 year for HER2 positive patients;
• Radiation therapy must begin no later than 12 weeks after the last dose of adjuvant chemotherapy or the last breast cancer surgery if no adjuvant chemotherapy;
• Patients have adequate organ function;
• Acquirement of informed consent.

Exclusion criteria

• Patients have received neoadjuvant systemic therapy;
• Clinical stage T4 or IV (metastatic) breast cancer, or presence of regional metastases before surgery;
• History of any prior ipsilateral or contralateral invasive breast cancer, history of other malignancies except for appropriately treated skin basal cell carcinoma and cervical carcinoma in situ;
• History of previous radiotherapy towards the ipsilateral chest/lymph nodes.
• The ipsilateral axillary lymph node dissection or other previous axillary surgery;
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, or psychiatric disease), inability to tolerate radiotherapy or systemic therapy if indicated;
• Current pregnancy and/or lactation;
• Inability or unwillingness to comply with protocol requirements.