Background
Phase III, open-label, non-inferiority RCT. 934 patients with clinical T1-3 N0 breast cancer and ≤1 sentinel node containing only micrometastasis (tumor deposits ≤2mm). Testing whether ALND could be safely omitted in sentinel node-micrometastasis-positive patients. Parallel to Z0011 (macrometastasis) but focused specifically on the micrometastasis subgroup, where prognostic significance and treatment implications were most debated.
Interventions and follow up
Arm A: No axillary dissection (no ALND after positive SLN biopsy)
Arm B: Axillary lymph node dissection (ALND)
Primary endpoint: Disease-free survival (DFS)
mFollow up: 9.7 years (10-yr analysis)
Arm B: Axillary lymph node dissection (ALND)
Primary endpoint: Disease-free survival (DFS)
mFollow up: 9.7 years (10-yr analysis)
Results
DFS (5-yr): 87.8% vs 84.4% (no ALND vs ALND), HR 0.78, 95% CI 0.55–1.11 — not inferior
OS (5-yr): 97.5% vs 97.6% — essentially identical
DFS (10-yr): 76.8% vs 74.9%, HR 0.85 — no significant difference
OS (5-yr): 97.5% vs 97.6% — essentially identical
DFS (10-yr): 76.8% vs 74.9%, HR 0.85 — no significant difference
Adverse events
Lymphedema: Significantly lower in the no-ALND arm throughout follow-up.
Neurologic/functional: Arm dysfunction and sensory disturbance lower without ALND.
Surgical: Surgical complication rates lower without formal dissection.
Neurologic/functional: Arm dysfunction and sensory disturbance lower without ALND.
Surgical: Surgical complication rates lower without formal dissection.
Conclusions
Omitting ALND in patients with ≤1 positive sentinel node containing only micrometastasis did not compromise DFS or OS compared to complete ALND. IBCSG 23-01 established that ALND is not required for sentinel node micrometastasis, substantially reducing surgical morbidity in this subgroup.
Key Limitations
The trial was underpowered for formal non-inferiority testing due to lower-than-expected event rates — the HR and CI, while favorable, do not meet a formal non-inferiority margin. Micrometastasis definition (≤2mm, isolated tumor cell clusters counted separately) requires careful pathology standardization. Not all patients received the same RT fields, potentially confounding axillary control. The trial enrolled predominantly BCS patients — generalizability to mastectomy patients is limited (as for Z0011). The ypN0(i+) category (isolated tumor cells) is distinct from micrometastasis and was not specifically analyzed.
Clinical Context
IBCSG 23-01 supports omitting ALND for sentinel node micrometastasis in BCS patients. Current guidelines (ASCO, ESMO) endorse SLNB alone for micrometastasis in patients receiving adequate adjuvant systemic therapy and WBI. Together with Z0011, AMAROS, and SENOMAC, these trials form the de-escalation evidence base for axillary surgery in early breast cancer. ESMO-MCBS score: N/A (surgical non-inferiority).