The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases.

In this multicenter, prospective randomized trial clinically node-negative breast cancer patients with 1-2 macrometastases in their sentinel lymph node biopsy, and an estrogen receptor positive, HER2-negative tumor, will be randomly assigned to either receive adjuvant locoregional radiotherapy, or no regional radiotherapy.

The main aim is to evaluate whether regional radiotherapy may safely be omitted in patients with limited lymph node metastasis and an estimated low risk of locoregional recurrence. Recurrence free survival after five years is the primary outcome, which for non-inferiority should not worsen more than 4.5 percentage units. Secondary outcomes are locoregional recurrence, regional nodal recurrence, new contralateral BC, distant recurrence free survival, overall survival, non-breast malignancies, cardiac disease, arm morbidity, and health-related quality of life.

Target volumes include:

Standard arm - The remaining breast/chest wall, axillary lymph node levels I-III, the supraclavicular lymph nodes (level IV), the interpectoral lymph nodes and in patients with a medial/central tumor also the internal mammary lymph nodes.

Intervention arm - The remaining breast after breast conserving surgery. No radiotherapy after mastectomy

Inclusion criteria

• Primary unifocal or multifocal invasive breast cancer T1-T2.
• Clinically N0.
• Macrometastasis (>2mm) in 1-2 lymph nodes at sentinel node biopsy.
• Oral and written consent.
• Age ≥ 18 years.
• All resection margins are tumor free (no tumor on ink).
• Primary tumor ER-positive, HER2-negative.

Exclusion criteria

• Regional or distant metastases outside the ipsilateral axilla.
• Previous RT towards the planned target area, i.e. the ipsilateral chest/lymph nodes.
• Neoadjuvant systemic therapy.
• Axillary lymph node dissection or other previous axillary surgery on the affected side.
• Prior history of invasive breast cancer.
• Pregnancy.
• Bilateral invasive breast cancer.
• Contraindication for radiotherapy or systemic treatment.
• Inability to absorb or understand the contents of the informed consent form; for example, through disability, inadequate language skills or dementia.
• Other invasive cancer within 5 years prior to breast cancer diagnosis