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N Engl J Med. 2015 Jul 23;373(4):307-16. doi: 10.1056/NEJMoa1415340.

Regional Nodal Irradiation in Early-Stage Breast Cancer.

Collaborators (206)

Grant N, Kwan W, Leong C, Balkwill S, Wilson DC, Carolan H, Goutsouliak V, Tyldesley S, Lim P, Weir L, Aquino-Parsons CF, Campbell G, Keyes M, Gelmon K, Olivotto I, Truong P, Wai E, Kader H, Blood PA, Alexander S, Roy I, Guay JP, Del Vecchio P, Jolicoeur M, Methot F, Ayllon J, Lavertu S, Fortin MA, Rousseau P, Germain I, Larochelle-Beland M, Vallieres I, Blondeau L, Laverdiere J, Dagnault A, Raymond PE, Fortin A, Butler J, Akra MA, Cooke AL, Nabid A, Bujold R, Ballivy O, Prevot G, Chafe S, Severin D, Lees A, Tankel K, Mehta N, Abdulkarim B, Amanie JO, Nijjar T, Greenland J, Basrur VR, Gopaul D, Whelan TJ, Dayes IS, Strang B, Reiter HI, Sussman J, Wright JR, Voruganti SM, Hodson I, McMillan WG, Levine M, Vujovic O, Lock MI, D'Souza D, Perera F, Read N, Yu E, Lambert C, Duclos M, Portelance L, David M, Shenouda G, Melnychuk D, Sultanem K, Giesbrecht J, Shao RH, Findlay B, Bowen J, Bissett RJ, Want D, Shehata S, Ackerman I, Paszat L, Benk V, Szumacher E, Tsao M, Pignol JP, Rakovitch E, Spayne J, Czarnota G, Wojcicka AM, Chow EL, Pritchard K, Meng J, Caudrelier JM, Grimard LJ, Lochrin C, Nair BD, Cross P, Rheaume D, Cwajna W, Rutledge RD, Nolan M, El-Gayed A, Skarsgard DP, Lirette A, Rojas F, Leblanc L, Falkson C, Anthes ML, Craighead P, Trotter T, Mackinnon J, Husain S, McKinnon G, Vallis K, Manchul L, Wells WA, Fyles A, Liu FF, Levin W, Cho J, Kane G, Koch A, McCready D, Feigan M, Papadatos G, Lonergan D, Peres H, Delaney G, Cox J, Bryant G, O'Brien P, Ludbrook J, Kumar M, Chua B, Blakey D, Phillips C, Bishop M, Guglani S, Drummond R, Sexton M, Lehman M, Harvey J, Gowda R, Penniment M, Carruthers S, Latham M, Joseph D, Taylor M, Spry N, Graham P, Ahern V, Parda D, Taylor J, Roig B, Champion L, Benda R, Kasper M, Moni J, Bains Y, Rearden T, Olson C, Schultz C, Berk L, Becker M, Leider P, Mueller W, White J, Zaren H, Lee R, Avizonis V, Petersen I, Vallow L, Tan W, Buskirk S, Ridings J, Bollinger J, Johnson N, Daconceicao A, Casey W, Kuettel M, Yap J, Saito N, Pruitt D, Jafar S, Gemer L, Lakomy D, Herman J, Stinson S, Chmura S, Pierce L, Streeter O, Wang W, Yao M, Soriano J, Clapper W, Jones J, Richardson J, Forman J, Kim H, Washington T.

Author information

From the Department of Oncology, McMaster University, and Juravinski Cancer Centre, Hamilton, ON (T.J.W., M.N.L.), Tom Baker Cancer Centre, Calgary, AB (I.A.O., P.C.), BC Cancer Agency-Vancouver Island Centre, Victoria, BC (I.A.O.), Queen's University and NCIC Clinical Trials Group, Kingston, ON (W.R.P., Y.M., J.-A.W.C., B.E.C.), University of Toronto and Sunnybrook Odette Cancer Centre, Toronto (I.A., K.I.P.), Centre Universitaire de Sherbrooke at Fleurimont Hospital, Sherbrooke, QC (A.N.), Université de Montréal, Montreal (P.R.), Laval University and L'Hôtel-Dieu de Québec, Quebec, QC (A.F.), Princess Margaret Hospital, Toronto (L.M., D.R.M.), Cross Cancer Institute, Edmonton, AB (S.C.), Nova Scotia Cancer Centre, Halifax (M.C.N), Northeastern Ontario Regional Cancer Centre, Sudbury (J.B.), and BC Cancer Agency-Vancouver Centre, Vancouver, BC (K.G.) - all in Canada; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.H.C.); Cancer Research UK-Medical Research Council Oxford Institute for Radiation Oncology, Oxford, United Kingdom (K.A.V.); Ohio State University Wexner Medical Center, Columbus (J.R.W.); and the University of Michigan Comprehensive Cancer Center, Ann Arbor (L.J.P.).



Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.


We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival.


Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001).


Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 number, NCT00005957.).

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