Level I-II Axillary Irradiation in Breast Cancer With Sentinel-Node Macro-metastases
Entire Regional Nodal Irradiation vs. Level I-II Axillary Irradiation in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macro-metastases (RELAX)：A Prospective, Multicenter, Randomized, Phase 3 Clinical Trial
Fudan University
1,608 participants
Oct 24, 2025
INTERVENTIONAL
Conditions
Summary
The RELAX trial is an open-label, multicenter, non-inferiority, randomized, phase 3 clinical trial. Multiple randomized trials have demonstrated the safety of omitting complete axillary-lymph-node dissection in patients with invasive breast cancer and limited sentinel lymph node metastases. However, the necessity and optimal extent of regional nodal irradiation remains uncertain. The aim of this study is 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.
Eligibility
Inclusion Criteria10
- 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 Criteria8
- 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.
Interventions
Radiation is delivered to the breast after BCS or chest wall after mastectomy, whole axillary lymph nodes (levels I-III) and supraclavicular 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. Both hypofractionated and conventional fractionated radiation therapy are permitted: the conventional fractionated regimen is 50 Gy in 25 fractions of 2 Gy; the hypofractionated schedule is 42.56 Gy in 16 fractions of 2.66 Gy after mastectomy, or 40.05 Gy in 15 fractions of 2.67 Gy after breast-conserving surgery. Tumor bed after breast-conserving surgery is at the discretion of the treating physician, boost doses will be 10\~16 Gy in 5\~8 fractions of 2 Gy or 10.68\~16.2 Gy in 4\~6 fractions of 2.67 Gy.
Radiation is delivered to the breast after BCS or chest wall after mastectomy and low axillary lymph nodes (levels I-II). Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant. Both hypofractionated and conventional fractionated radiation therapy are permitted: the conventional fractionated regimen is 50 Gy in 25 fractions of 2 Gy; the hypofractionated schedule is 42.56 Gy in 16 fractions of 2.66 Gy after mastectomy, or 40.05 Gy in 15 fractions of 2.67 Gy after breast-conserving surgery. Tumor bed after breast-conserving surgery is at the discretion of the treating physician, boost doses will be 10\~16 Gy in 5\~8 fractions of 2 Gy or 10.68\~16.2 Gy in 4\~6 fractions of 2.67 Gy.
Locations(15)
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NCT07469267