Breast
De-escalating axillary surgery in a setting where the nodal basin is still being irradiated.
SENOMAC NCT02240472
ForcN0 T1-T3 breast cancer, 1-2 sentinel-node macrometastases
HR 0.89
95% CI 0.66-1.19, NI met (margin 1.44); primary OS not yet reported
TL;DR5-yr RFS 89.7% vs 88.7%, HR 0.89 (0.66-1.19): omitting completion ALND noninferior, with nodal RT given in ~90% of both arms.
Nodal RT with nodal target volumes reached ~90% in both arms (89.9% vs 88.4%), so SENOMAC validates dropping completion ALND within regional nodal irradiation, not omitting axillary treatment. For the RT reader it positions nodal RT as the axillary treatment when SNB shows 1-2 macromets; it does not test omitting both surgery and RT.
8 details 4 trials watching
Phase 3 noninferiority RCT, 1:1, N=2766 enrolled (2540 per-protocol), 67 sites across 5 countries; median follow-up 46.8 mo. Reports the prespecified secondary RFS; primary OS not yet reported.
cN0 T1-T3 breast cancer with 1-2 sentinel-node macrometastases (>2mm). Extends eligibility beyond Z0011 to mastectomy, T3, extracapsular extension, and men.
Nodal RT including nodal target volumes reached 89.9% (SNB-only) and 88.4% (cALND). ALND omission was therefore tested within regional nodal irradiation, not as omission of axillary treatment.
Primary: overall survival (not reported in source). This analysis: prespecified secondary recurrence-free survival, per-protocol and modified ITT.
Noninferiority met: the upper confidence bound stayed below the prespecified 1.44 margin (P<0.001) across 191 recurrence-or-death events.
| Endpoint | SNB only | cALND |
|---|---|---|
| 5-yr RFS | 89.7% (87.5-91.9) | 88.7% (86.3-91.1) |
| HR recurrence/death | 0.89 (0.66-1.19) | ref |
Consistent with Z0011 (breast-conserving + whole-breast RT) and AMAROS (axillary RT replacing ALND), both null for ALND benefit at 10 yr. SENOMAC adds the macromet-only, mastectomy/T3/ECE/male groups in a larger cohort.
This is the secondary RFS endpoint, not the OS primary, at a 46.8-mo median follow-up short for ER+ biology. The HR 1.44 noninferiority margin is generous, and ~90% nodal RT confounds attribution to surgical omission alone.
Randomised phase 3 noninferiority; prespecified secondary RFS met, extends Z0011/AMAROS de-escalation to mastectomy/T3/ECE/men. Primary OS not yet reported.
In cN0 breast cancer with 1-2 sentinel-node macrometastases who receive regional nodal RT, this supports omitting completion ALND, including mastectomy, T3, extracapsular extension, and men; it does not extend to patients treated without nodal radiotherapy.
- Overall survival (primary endpoint) result still pending
- Can nodal RT be omitted alongside ALND in this population? recruiting Evaluating Omitting of Internal Mammary Irradiation Among Early Stage Intermediate Risk (N1) Breast Cancer Phase NAn=214 · primary completion 2025-10 · randomized omit internal mammary RT in N1active Postmastecomy Internal Mammary Nodal Irradiation for High-risk Breast Cancer Patients Phase 3n=2400 · primary completion 2025-11 · phase 3 IMN RT vs no IMN RT, DFS endpointrecruiting The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases. Phase NAn=1350 · primary completion 2028-12 · omit regional RT, 1-2 SN macromets, ER+/HER2-recruiting RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer Phase NAn=540 · primary completion 2029-08 · RecurIndex-guided RNI avoidance in N1
- Durability beyond 5 years in ER+ disease