ACOSOG Z1071 (Alliance)

Design, population and eligibility

Treatment and comparator

Procedure evaluated: Sentinel lymph-node surgery after neoadjuvant chemotherapy, followed by completion ALND in the study to establish the reference standard. Dual mapping with blue dye and radiolabelled colloid was encouraged.

Comparator: ALND served as the reference standard, not as a randomized treatment arm. The study was designed to estimate the false-negative rate (FNR).

Primary and secondary endpoints

Primary endpoint: FNR of SLN surgery among initially cN1 patients with at least two sentinel nodes examined. Secondary analyses included nodal pCR, mapping technique and number of sentinel nodes retrieved.

Key efficacy results

Among 525 cN1 patients with ≥2 SLNs removed, 215 had no residual nodal cancer, giving nodal pCR 41.0% (95% CI 36.7–45.3). Among patients with residual nodal disease, 39 had negative SLNs but positive ALND nodes: FNR 12.6% (90% Bayesian credible interval 9.85–16.05%). This exceeded the prespecified 10% target.

FNR was 10.8% with dual tracer versus 20.3% with a single mapping agent; 9.1% with ≥3 SLNs versus 21.1% with two SLNs. In the clipped-node follow-up, FNR was 6.8% when the clipped node was retrieved within the SLN specimen versus 19.0% when the clipped node was found only in the ALND specimen.

Source-reported outcome visualization

False-negative rate in cN1 patients; lower is better.

These are diagnostic-accuracy measures, not recurrence or survival rates. The clipped-node analysis is a subsequent technical analysis of the same trial cohort.

Absolute effect

NNT/NNH is not applicable to the diagnostic-accuracy primary endpoint. The clinically relevant measure is FNR: 12.6% overall in the specified ≥2-node subgroup, improved with dual tracer, retrieval of ≥3 nodes and confirmation of the clipped node.

Trial-specific toxicity and treatment burden

Because ALND was performed as a reference standard, the trial does not compare surgical morbidity between SLNB alone and ALND. It therefore cannot quantify an NNT/NNH for lymphedema or shoulder morbidity. The clinical rationale for improved staging is to avoid unnecessary ALND when nodal response is complete while not missing residual disease.

Quality of life and patient-reported outcomes

No randomized QoL comparison was conducted. Patient-reported morbidity and arm function were not the primary focus of this diagnostic-accuracy study.

Subgroups and applicability

FNR improved with dual tracer and retrieval of ≥3 nodes. In the clipped-node follow-up, confirming removal of the originally biopsy-positive clipped node reduced FNR to 6.8%. These technical findings underpin targeted axillary dissection (TAD); they do not independently validate omission of ALND for residual nodal disease.

Current-practice context · reviewed 2 November 2026

Contemporary post-NACT axillary staging in initially node-positive patients generally emphasizes marking the biopsy-proven positive node, dual-tracer mapping, retrieval of the clipped node and multiple sentinel nodes. Residual nodal disease still requires management according to current surgical and regional nodal treatment guidance.

Limitations and critical interpretation

This was not randomized to SLNB alone versus ALND and cannot prove oncologic safety of omitting ALND. FNR was above the prespecified threshold in the primary analysis. The clipped-node analysis is a later technical subset analysis, not a separate randomized trial.

Bottom line: Z1071 showed that conventional SLNB after NACT in initially cN1 disease had an unacceptably high FNR. Its legacy is technical refinement—dual tracer, ≥3 nodes and clipped-node retrieval—not blanket ALND omission.

Primary sources and follow-up publications

1. ACOSOG Z1071 primary report, JAMA 2013
2. Clipped-node follow-up analysis, Annals of Surgery 2016
3. Z1071 registry

All outcome values above are transcribed from the linked trial reports or their prespecified follow-up publications. Unreported values are not imputed. No NNT is derived from median survival.