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N Engl J Med. 2015 Jul 23;373(4):317-27. doi: 10.1056/NEJMoa1415369.

Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.

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From the Department of Radiation Oncology, Radboud University Medical Center, Nijmegen (P.M.P.), Department of Radiation Oncology, Institute Verbeeten, Tilburg (P.M.P., K.D.W.), Department of Radiation Oncology, Medisch Centrum Haaglanden, The Hague (H.S.), Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (H.S., C.R.), Department of Radiation Oncology, Institute for Radiation Oncology Radiotherapeutisch Instituut Stedendriehoek en Omstreken, Deventer (E.V.), Department of Radiation Oncology, Academic Medical Center (G.T.), and Department of Radiation Oncology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (H.B.), Amsterdam - all in the Netherlands; European Organization for Research and Treatment of Cancer (EORTC) Headquarters (S.C., L.C.) and Department of Radiation Oncology, University Hospital Saint-Luc, Université Catholique de Louvain (C.K.), Brussels, and Department of Radiation Oncology, University Hospital Gasthuisberg, Leuven (E.V.L., W.V.B.) - all in Belgium; Department of Radiation Oncology, Charité University Medicine Berlin, Berlin (V.B., S.M.), and Department of Radiation Oncology, University Hospital, Tübingen (N.W.) - both in Germany; Department of Radiation Oncology, Institut Curie, Paris (A.F.), Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon (P.M., I.B.), Department of Radiation Oncology, Université François Rabelais, Tours (I.B.), and Department of Radiation Oncology, Gustave Roussy Cancer Center, Villejuif (H.M.) - all in France; Department of Radiation Oncology, Ospedale Regionale di Bellinzona e Valli, Bellinzona (M.V.), and Department of Radiation Oncology, University Hospital Zurich (C.G.) - both in Switzerland; Department of Radiation Oncology, Sant'Anna Hospital, Como, Italy (M.V., L.S.); Department of Radiation Oncology, Rambam Medical Center, Haifa, Israel (A.K.); and Grupo Oncológico Cooperativo Chileno de Investigación, Santiago, Chile (R.A.).



The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown.


We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer.


Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest.


In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; number, NCT00002851.).

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