SENOMAC

Background

Phase III, open-label, non-inferiority RCT. 2540 patients with clinically node-negative breast cancer (cT1-3 N0) and sentinel lymph node macrometastasis (≥2mm) who had undergone BCS or mastectomy. Broader eligibility than ACOSOG Z0011 — included mastectomy patients, patients with ≥3 positive nodes in the final analysis, and patients receiving any systemic therapy. SENOMAC tested whether complete ALND could be omitted in SLN macrometastasis-positive patients regardless of surgical approach.

Interventions and follow up

Arm A: Sentinel lymph node biopsy alone (no further axillary surgery)
Arm B: Axillary lymph node dissection (complete, levels I–III)
Primary endpoint: Breast cancer-specific survival (BCSS) at 5 years (non-inferiority)
mFollow up: 46.8 months

Results

DFS (3-yr): 89.7% vs 88.1% (SLNB vs ALND), HR 0.89, 95% CI 0.71–1.12 — non-inferior
Breast cancer-specific survival: No significant difference at 3 years
Axillary recurrence: Low rates in both arms, no significant difference

Adverse events

Lymphedema: Any grade 11% (SLNB) vs 20% (ALND) at 3 years — significantly lower with SLNB alone.
Neurologic/functional: Sensory disturbance and restricted arm movement also lower in the SLNB arm.
Surgical: Complications from surgery were less frequent in the SLNB arm.

Conclusions

SLNB alone was non-inferior to ALND for short-term DFS in breast cancer patients with SLN macrometastasis, including mastectomy patients — extending the Z0011 principle to a broader surgical population. Lymphedema and surgical morbidity were significantly lower with SLNB alone.

Key Limitations

Follow-up was relatively short (median ~47 months) — the primary endpoint of BCSS at 5 years is not yet mature; current results are on the DFS surrogate. Mastectomy patients in SENOMAC may not have received full-breast RT as in Z0011 — the mechanism of equivalent axillary control without ALND may differ between BCS and mastectomy patients. Systemic therapy use was heterogeneous (neoadjuvant and adjuvant, including CDK4/6i and immunotherapy in recent patients). ALND arms in SENOMAC and Z0011 had very low recurrence rates regardless of treatment — systemic therapy may be the dominant driver of locoregional control.

Clinical Context

SENOMAC is the largest RCT addressing axillary management in SLN-positive BC and extends SLNB-alone safety to mastectomy patients. Together with Z0011, AMAROS, and IBCSG 23-01, SENOMAC completes the evidence base supporting de-escalation of axillary surgery. Current ESMO/ASBrS guidelines support SLNB-alone for cN0 patients with 1–2 positive SLNs undergoing BCS + WBI; SENOMAC strengthens the case for extending this to mastectomy patients with macrometastasis. ESMO-MCBS score: N/A.

References