Background
Phase III RCT (EORTC 22922/10925). 4,004 patients with stage I–III breast cancer after BCS or mastectomy, with centrally or medially located tumors or axillary node involvement, who had received standard RT to the breast/chest wall ± axilla and supraclavicular fossa. All patients also received adjuvant systemic therapy. Randomized to additional internal mammary and medial supraclavicular (IM-MS) nodal irradiation vs no IM-MS RT.
Interventions and follow up
Arm A: Breast/CW RT + axillary/SCF RT + internal mammary/medial supraclavicular RT (IM-MS)
Arm B: Breast/CW RT + axillary/SCF RT alone (no IM-MS RT)
Primary endpoint: Disease-free survival (DFS)
mFollow up: Median 10.9 year
Arm B: Breast/CW RT + axillary/SCF RT alone (no IM-MS RT)
Primary endpoint: Disease-free survival (DFS)
mFollow up: Median 10.9 year
Results
10-year DFS: 72.1% (IM-MS RT) vs 69.1% (no IM-MS RT), HR 0.89 (95% CI 0.80–0.99), P=.04
10-year OS: 82.3% vs 80.9%, HR 0.87 (95% CI 0.76–1.00), P=.056 — borderline significant
10-year distant metastasis-free survival: 78.0% vs 75.0%, HR 0.86, P=.02
10-year breast cancer mortality: 12.5% vs 14.4%, P=.02
10-year OS: 82.3% vs 80.9%, HR 0.87 (95% CI 0.76–1.00), P=.056 — borderline significant
10-year distant metastasis-free survival: 78.0% vs 75.0%, HR 0.86, P=.02
10-year breast cancer mortality: 12.5% vs 14.4%, P=.02
Adverse events
Main adverse events: IM-MS RT was not associated with significant excess cardiac or pulmonary toxicity at 10 years. Grade ≥2 pneumonitis and cardiac events were low in both arms with modern RT techniques used in this trial.
Conclusions
Irradiation of the internal mammary and medial supraclavicular nodes provides a statistically significant improvement in DFS (absolute 3%) and a borderline significant improvement in OS (absolute 1.4%) at 10 years in patients with medially located or node-positive breast cancer. IM-MS RT reduces distant metastasis and breast cancer mortality, supporting IMN irradiation in appropriately selected patients.
Key Limitations
Key Limitations: Small absolute benefits (3% DFS, 1.4% OS) may not justify the toxicity risk in all patients, particularly those with left-sided breast cancer where cardiac exposure is higher. Not all patients with lymph node involvement underwent SLNB — staging by older ALND methods. Simultaneous publication with MA-20 (NEJM 2015) showed similar directional results but not all subgroup analyses are consistent between the two trials. IMN RT adds complexity and potential cardiac/pulmonary toxicity that requires individualized risk-benefit assessment.
Clinical Context
Together with MA-20, EORTC 22922 established regional nodal irradiation (including IMN) as a standard consideration for patients with medially located or node-positive breast cancer. ESTRO guidelines incorporate IMN irradiation for patients at risk. In clinical practice, IMN irradiation is more routinely included in patients with N2-3 disease or medial/central tumors with nodal involvement. For N1 patients, shared decision-making is appropriate.
References