Background
Phase III non-inferiority RCT (AMAROS — After Mapping of the Axilla: Radiotherapy Or Surgery). 1,425 patients with T1-T2 invasive breast cancer (BCS or mastectomy) and a positive sentinel lymph node (SLN). Randomized to complete axillary lymph node dissection (ALND) vs axillary RT (50 Gy in 25 fractions to the axilla). All patients received WBI after BCS. Enrolled at 34 centers in 9 European countries.
Interventions and follow up
Arm A: Axillary RT: 50 Gy in 25 fractions to levels I–III axilla
Arm B: Completion ALND (full axillary dissection)
Primary endpoint: Axillary recurrence at 5 years (non-inferiority)
mFollow up: Median 6.1 year
Arm B: Completion ALND (full axillary dissection)
Primary endpoint: Axillary recurrence at 5 years (non-inferiority)
mFollow up: Median 6.1 year
Results
5-year axillary recurrence: 1.19% (axillary RT) vs 0.43% (ALND), P=.33 — non-inferiority criterion met
5-year DFS: 82.7% (RT) vs 86.9% (ALND), P=.18 — not significant
5-year OS: 92.5% (RT) vs 93.3% (ALND), P=.34 — not significant
5-year lymphedema: 14% (RT) vs 28% (ALND), P<.001 — significantly less with RT
5-year shoulder/arm morbidity: Significantly lower impairment with axillary RT
5-year DFS: 82.7% (RT) vs 86.9% (ALND), P=.18 — not significant
5-year OS: 92.5% (RT) vs 93.3% (ALND), P=.34 — not significant
5-year lymphedema: 14% (RT) vs 28% (ALND), P<.001 — significantly less with RT
5-year shoulder/arm morbidity: Significantly lower impairment with axillary RT
Adverse events
Main adverse events: ALND: lymphedema 28%, shoulder stiffness, sensory changes. Axillary RT: lymphedema 14%, fibrosis, brachial plexopathy (rare). Radiation pneumonitis: not significantly different. Overall morbidity was substantially lower with axillary RT than ALND.
Conclusions
Axillary RT is non-inferior to ALND in controlling axillary disease in patients with SLN-positive breast cancer, with significantly lower rates of lymphedema and arm morbidity. This provides an alternative to ALND for patients with positive SLNs who require axillary treatment, particularly those undergoing mastectomy (where WBI-based axillary coverage from Z0011 does not apply).
Key Limitations
Key Limitations: 5-year follow-up is relatively short for assessment of late recurrence; longer follow-up data needed. Trial enrolled both BCS and mastectomy patients, but BCS patients receiving WBI may have had inadvertent axillary coverage, similar to Z0011. The difference in 5-year DFS (4.2%) was not statistically significant but may reflect a real difference with longer follow-up. Non-inferiority margin was pre-specified; axillary RT arm had numerically higher axillary recurrence (1.19% vs 0.43%). Excluded patients with 3+ positive SLNs.
Clinical Context
AMAROS established axillary RT as an alternative to ALND for SLN-positive patients, with superior limb function outcomes. It is particularly relevant for mastectomy patients with positive SLNs (where Z0011 does not apply) and for patients in whom ALND morbidity is a significant concern. Combined with Z0011 (which established SLNB alone for BCS patients with 1-2 positive SLNs receiving WBI), AMAROS and Z0011 have collectively transformed axillary management in early breast cancer.
References
References: Donker M et al, Lancet Oncol 2014 (AMAROS)