LBA1003 Background: Randomized trials have demonstrated that locoregional radiation after mastectomy reduces locoregional recurrence and improves overall survival (OS) in women with node positive breast cancer treated with adjuvant systemic therapy. MA.20 evaluated the addition of regional nodal irradiation (RNI) to whole breast irradiation (WBI) following breast conserving surgery (BCS). Methods: Women with high risk node-negative or node-positive breast cancer treated with BCS and adjuvant chemotherapy and/or endocrine therapy were stratified by positive nodes, axillary nodes removed, chemo- and endocrine therapy and randomized to WBI (50Gy in 25 fractions +/- boost irradiation) or WBI plus RNI (45Gy in 25 fractions) to the internal mammary, supraclavicular, and high axillary lymph nodes. The primary outcome was OS. The Data Safety Monitoring Committee approved the analysis plan for the protocol specified interim analysis of relapse patterns, survival and toxicity at 5 years. Upon review of the data, they recommended release of the results. Results: Between March 2000 to March 2007, 1,832 women were randomly assigned to WBI+RNI (916) or WBI (916). Median follow-up was 62 months. Characteristics of the study population were: mean age, 53.3 years; node negative, 10%; 1-3 positive nodes, 85%; &gt; 4 positive nodes, 5%; adjuvant chemotherapy, 91%; and adjuvant endocrine therapy, 71%. WBI+RNI in comparison to WBI alone was associated with an improvement in isolated locoregional disease free survival (DFS; HR=.59, p=.02, 5 year risk: 96.8% and 94.5% respectively), distant DFS (HR=.64, p=.002, 5 year risk: 92.4% and 87.0% respectively), DFS (HR=.68, p=.003, 5 year risk: 89.7% and 84.0% respectively) and OS (HR=.76, p=.07, 5 year risk: 92.3% and 90.7% respectively). WBI+RNI in comparison to WBI was associated with an increase in grade 2 or greater pneumonitis (1.3% and 0.2% respectively, p=.01), and lymphedema (7.3% and 4.1% respectively, p=.004). Conclusions: The majority of women with node positive breast cancer are now managed by BCS followed by WBI and adjuvant systemic therapy. Results from MA.20 demonstrate that additional RNI reduces the risk of locoregional and distant recurrence, and improves DFS with a trend in improved OS.

NCIC-CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer.