NEONOD 2: Rationale and design of a multicenter non-inferiority trial to assess the effect of axillary surgery omission on the outcome of breast cancer patients presenting only micrometastasis in the sentinel lymph node after neoadjuvant chemotherapy

Sentinel lymph node biopsy alone, without complete axillary lymph node dissection, is the standard treatment of the axilla nodal chain in early-stage breast cancer patients presenting a negative sentinel lymph node. The updated results of the IBCSG 23-01 randomized trial recently provided evidence that this approach could be extended to early-stage breast cancer patients presenting only micrometastasis in the sentinel lymph node. On the other hand, patients with large operable or locally advanced breast cancer and clinically positive lymph nodes currently receive neoadjuvant chemotherapy and sentinel lymph node biopsy, which is then followed by complete axillary node dissection if the sentinel lymph node till contains tumor residue, regardless of the extent of nodal disease. Assuming that patients presenting only a micrometastatic sentinel lymph node after neoadjuvant chemotherapy are clinically equivalent to the IBCSG 23-01 early-breast cancer patients with only micrometastatic sentinel node, then complete axillary dissection would be unneeded also in these subset of patients in the neoadjuvant setting. The multicenter uncontrolled non-inferiority trial NEONOD 2 we here present was designed to assess this hypothesis, i.e. whether or not omission of complete axillary nodal clearance worsens prognosis in patients with sentinel node resulting only micrometastatic after neoadjuvant chemotherapy.