The Absolute Effect / Evidence / Breast Cancer
SENOMAC
Clinical question: In clinically node-negative breast cancer with one or two sentinel-node macrometastases, can completion ALND be omitted?
Registry: NCT02240472 · One underlying study; follow-up publications consolidated.
Phase III · randomized · non-inferiority · Evidence cut-off: 8 November 2026
Design, population and eligibility
International randomized non-inferiority trial comparing sentinel-node biopsy alone with completion ALND in clinically node-negative patients with one or two sentinel-node macrometastases.
2,766 enrolled; per-protocol population 2,540 (1,335 sentinel-node biopsy only; 1,205 ALND).
Clinically node-negative T1–T3 breast cancer with one or two sentinel-node macrometastases >2 mm. Most patients received regional nodal radiotherapy.
2024 peer-reviewed RFS analysis median follow-up 46.8 months; 2026 ASCO primary OS and patient-reported morbidity update median follow-up 60.1 months.
Treatment and comparator
Intervention: Sentinel-node biopsy alone; no completion ALND.
Comparator: Completion axillary lymph-node dissection.
Primary endpoint: Overall survival; recurrence-free survival is a reported secondary endpoint.
Key efficacy outcomes
5-year RFS (2024): 89.7% omission vs 88.7% ALND HR 0.89 (95% CI 0.66–1.19); p<0.001 for non-inferiority.
5-year OS (2026 ASCO abstract): 94.4% omission vs 93.4% ALND HR 0.84 (95% CI 0.64–1.12); between-arm p=0.238.
Arm physical function: Better with omission at 3 and 5 years Lymph-ICF mean difference 6.14 at 3 years and 5.71 at 5 years; p<0.001.
The 2024 RFS analysis met the prespecified non-inferiority criterion. The 2026 ASCO abstract reports 5-year OS of 94.4% vs 93.4% (HR 0.84, 95% CI 0.64–1.12); this is meeting-abstract evidence, not yet a full peer-reviewed OS publication.
Absolute outcome visualization
Five-year recurrence-free survival and overall survival.
Bars display source-reported rates; no rates are inferred from medians. Single-arm outcomes are not comparative effects.
NNT / NNH
No NNT for survival: this is a non-inferiority de-escalation trial, not evidence that omission improves survival. The RFS comparison met its prespecified NI margin.
A single NNH for arm morbidity is not calculated from questionnaire scores. The patient-reported physical-function and symptom scales significantly favoured omission.
Toxicity, grade 3–5 harms and treatment burden
Regional nodal RT was delivered to 89.9% of the omission group and 88.4% of the ALND group. Lymph-ICF arm physical function and EORTC QLQ-BR23 arm symptoms favoured omission at years 3 and 5. Global QoL did not differ significantly. Do not attribute all morbidity differences solely to surgery without considering RT.
Omission avoids completion axillary surgery, reducing operative recovery and arm morbidity. Most patients still received nodal irradiation; this is not evidence to omit all axillary treatment.
Quality of life and patient-reported outcomes
EORTC QLQ-C30 and BR23 were collected. Global health-related QoL did not differ significantly; arm physical function and symptoms favoured omission.
Subgroups and applicability
Includes selected patients with one or two macrometastatic sentinel nodes and clinically node-negative axilla. Applicability to bulky nodal disease, ≥3 positive sentinel nodes or gross extranodal extension is not established.
Critical appraisal and limitations
The 2024 RFS report is secondary endpoint; primary OS and patient-reported outcomes were presented in a 2026 meeting abstract. Nodal RT was common in both groups, limiting extrapolation to no axillary RT.
Clinical interpretation
SENOMAC supports omission of completion ALND in selected patients with one or two sentinel-node macrometastases, usually with regional nodal RT. It does not test omission of all axillary therapy.
Contemporary-practice note (8 November 2026): Historical trial results are separated from current practice. Comprehensive guideline-level freshness review remains pending for this batch; use current disease-specific guidance and multidisciplinary context.