The Absolute Effect / Evidence / Breast Cancer
MA.20 (NCIC CTG)
Clinical question: After breast-conserving surgery, does adding regional nodal irradiation to whole-breast irradiation improve disease control in node-positive or high-risk node-negative breast cancer?
Registry: NCT00005957 · One underlying study; aliases and follow-up publications consolidated.
Design, population and eligibility
Phase III randomized trial
1,832 women randomized: 916 whole-breast irradiation plus RNI and 916 whole-breast irradiation alone. Median follow-up 9.5 years.
Node-positive or high-risk node-negative breast cancer treated with breast-conserving surgery and adjuvant systemic therapy. RNI included internal mammary, supraclavicular and axillary lymph nodes.
Follow-up and endpoint maturity are stated with the reported efficacy results; further long-term updates are noted where applicable.
Treatment and comparator
Whole-breast irradiation plus regional nodal irradiation (internal mammary, supraclavicular and axillary nodes) versus whole-breast irradiation alone. The RNI prescription was protocol-specified; systemic therapy was given in both arms.
Primary and secondary endpoints
Primary endpoint: overall survival. Secondary endpoints included DFS, isolated locoregional DFS and distant DFS.
Key efficacy results
At 10 years, DFS was 82.0% with RNI versus 77.0% without RNI; HR 0.76 (95% CI 0.61–0.94; P=0.01). OS was 82.8% versus 81.8%; HR 0.91 (95% CI 0.72–1.13; P=0.38). RNI reduced breast cancer recurrence, including distant recurrence, but did not significantly improve OS at this follow-up.
Source-reported outcome visualization
Ten-year DFS and OS.
DFS benefit was statistically significant; OS difference was not. These are separate endpoints and should not be conflated.
Absolute effect
10-year DFS absolute improvement was 5.0 percentage points (82% vs 77%); approximate NNT 20 to prevent one DFS event by 10 years. OS improved by 1.0 point but was not statistically significant (P=0.38); no OS NNT is assigned.
Trial-specific toxicity and treatment burden
Grade ≥2 acute pneumonitis: 1.2% with RNI versus 0.2% without (P=0.01). Grade ≥2 lymphedema: 8.4% versus 4.5% (P=0.001). Approximate NNH 26 for one additional grade ≥2 lymphedema event by the reported follow-up, and NNH 100 for one additional grade ≥2 pneumonitis event; these are based on observed absolute differences and should be interpreted with caution. Cardiac and pulmonary dose-sparing techniques are important in current practice.
Quality of life and patient-reported outcomes
The trial demonstrated disease-control benefit but does not establish an overall QoL advantage. Increased lymphedema and pneumonitis are clinically relevant trade-offs.
Subgroups and applicability
Most participants had one to three positive nodes. The trial also enrolled selected high-risk node-negative patients, but benefit in that subgroup is less certain. The study does not isolate the contribution of each nodal basin.
Current-practice context · reviewed 3 November 2026
RNI should be considered in node-positive and selected high-risk patients after breast-conserving surgery, particularly with higher nodal burden. Modern contouring, DIBH, IMRT and individualized cardiac/pulmonary sparing influence the therapeutic ratio.
Limitations and critical interpretation
The primary OS endpoint was not significantly improved. The study predates several modern systemic regimens and contemporary radiation planning. The contribution of internal mammary versus supraclavicular/axillary irradiation cannot be separated.
Bottom line: MA.20 establishes a DFS and recurrence benefit from RNI in appropriately selected node-positive/high-risk patients, at the cost of more lymphedema and pneumonitis; it does not prove an OS benefit.
Primary sources and follow-up publications
Outcome values are sourced from the linked reports. Unreported values are not imputed. NNT/NNH is only stated when an explicit fixed-time absolute difference supports a defensible calculation; no NNT is derived from median survival.