Sentinel Lymph Node Biopsy Alone Is Non‑Inferior to Completion ALND in Clinically Node‑Negative Breast Cancer (SENOMAC Trial)

Trial Overview

The SENOMAC trial was a prospective, randomized, phase III non‑inferiority study that showed sentinel lymph node biopsy (SLNB) alone provides oncologic outcomes comparable to completion axillary lymph node dissection (ALND) in patients with clinically node‑negative T1‑T3 breast cancer and 1–2 sentinel node macrometastases, while markedly reducing arm morbidity and improving patient‑reported outcomes. 1
A total of 2,540 patients with clinically node‑negative primary T1‑T3 breast cancer and 1–2 macrometastatic sentinel nodes were enrolled and randomized 1:1 to SLNB only (≈1,335 patients) or completion ALND (≈1,205 patients). 2 1
Pre‑operative axillary ultrasound was required for all participants. 2
Both breast‑conserving surgery and mastectomy were represented (≈36 % mastectomy), extending the applicability beyond prior trials. 2 3

At a median follow‑up of 46.8 months, the 5‑year recurrence‑free survival (RFS) was 89.7 % (95 % CI 87.5–91.9) in the SLNB‑only arm and 88.7 % (95 % CI 86.3–91.1) in the ALND arm, confirming non‑inferiority of SLNB alone. 3
The trial’s primary endpoint of overall survival has not yet been reported. 1

Regional nodal radiation therapy (RT) was administered to the vast majority of participants in both arms (≈89 % overall). 1
Per protocol, RT encompassed the breast or chest wall together with the regional nodal basins, supporting the use of comprehensive nodal irradiation when macrometastatic node‑positive disease is present. 2

ASCO (2025): Endorses omission of ALND in patients with cT1‑T3 N0 tumors and 1–2 positive sentinel node macrometastases provided that regional nodal RT is delivered, extending the ACOSOG Z0011 findings to a broader population. 2
NCCN (2025): Expands criteria for ALND omission to include cT1‑T3 tumors (previously limited to T1‑T2), patients undergoing mastectomy, and those with 1–2 sentinel node macrometastases, contingent on adjuvant RT that intentionally includes the regional nodes. 4 5 1
- The NCCN panel notes limited evidence for T3 tumors and for patients with ≥3 positive sentinel nodes. 4

Regional nodal RT must be incorporated into the treatment plan (delivered to ~89 % of trial participants). 2 1
Pre‑operative axillary ultrasound is mandatory to confirm clinically node‑negative status. 2
Eligibility is restricted to 1–2 sentinel node macrometastases only. 1
Patients must have clinically node‑negative disease at presentation.

A post‑hoc analysis estimated that performing completion ALND in 104 patients to identify ≥4 nodal metastases (pN2‑3) for adjuvant abemaciclib would cause severe or very severe arm morbidity in 9 patients, leading the authors to recommend against routine ALND solely for CDK4/6‑inhibitor eligibility. 1