Lancet. 2011 Nov 12;378(9804):1707-16. Epub 2011 Oct 19.

Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials.

Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R.

Collaborators (690)

Albain K, Anderson S, Arriagada R, Barlow W, Bergh J, Bliss J, Buyse M, Cameron D, Carrasco E, Clarke M, Correa C, Coates A, Collins R, Costantino J, Cutter D, Cuzick J, Darby S, Davidson N, Davies C, Davies K, Delmestri A, Di Leo A, Dowsett M, Elphinstone P, Evans V, Ewertz M, Gelber R, Gettins L, Geyer C, Goldhirsch A, Godwin J, Gray R, Gregory C, Hayes D, Hill C, Ingle J, Jakesz R, James S, Kaufmann M, Kerr A, MacKinnon E, McGale P, McHugh T, Norton L, Ohashi Y, Paik S, Pan HC, Perez E, Peto R, Piccart M, Pierce L, Pritchard K, Pruneri G, Raina V, Ravdin P, Robertson J, Rutgers E, Shao YF, Swain S, Taylor C, Valagussa P, Viale G, Whelan T, Winer E, Wang Y, Wood W, Abe O, Abe R, Enomoto K, Kikuchi K, Koyama H, Masuda H, Nomura Y, Ohashi Y, Sakai K, Sugimachi K, Toi M, Tominaga T, Uchino J, Yoshida M, Haybittle JL, Leonard CF, Calais G, Geraud P, Collett V, Davies C, Delmestri A, Sayer J, Harvey VJ, Holdaway IM, Kay RG, Mason BH, Forbes JF, Wilcken N, Bartsch R, Dubsky P, Fesl C, Fohler H, Gnant M, Greil R, Jakesz R, Lang A, Luschin-Ebengreuth G, Marth C, Mlineritsch B, Samonigg H, Singer CF, Steger GG, Stöger H, Canney P, Yosef HM, Focan C, Peek U, Oates GD, Powell J, Durand M, Mauriac L, Di Leo A, Dolci S, Larsimont D, Nogaret JM, Philippson C, Piccart MJ, Masood MB, Parker D, Price JJ, Lindsay MA, Mackey J, Martin M, Hupperets PS, Bates T, Blamey RW, Chetty U, Ellis IO, Mallon E, Morgan DA, Patnick J, Pinder S, Olivotto I, Ragaz J, Berry D, Broadwater G, Cirrincione C, Muss H, Norton L, Weiss RB, Abu-Zahra HT, Portnoj SM, Bowden S, Brookes C, Dunn J, Fernando I, Lee M, Poole C, Rea D, Spooner D, Barrett-Lee PJ, Mansel RE, Monypenny IJ, Gordon NH, Davis HL, Cuzick J, Lehingue Y, Romestaing P, Dubois JB, Delozier T, Griffon B, Mace Lesec'h J, Rambert P, Mustacchi G, Petruzelka, Pribylova O, Owen JR, Harbeck N, Jänicke F, Meisner C, Schmitt M, Thomssen C, Meier P, Shan Y, Shao YF, Wang X, Zhao DB, Chen ZM, Pan HC, Howell A, Swindell R, Burrett JA, Clarke M, Collins R, Correa C, Cutter D, Darby S, Davies C, Davies K, Delmestri A, Elphinstone P, Evans V, Gettins L, Godwin J, Gray R, Gregory C, Hermans D, Hicks C, James S, Kerr A, MacKinnon E, Lay M, McGale P, McHugh T, Sayer J, Taylor C, Wang Y, Albano J, de Oliveira CF, Gervásio H, Gordilho J, Johansen H, Mouridsen HT, Gelman RS, Harris JR, Hayes D, Henderson C, Shapiro CL, Winer E, Christiansen P, Ejlertsen B, Ewertz M, Jensen MB, Møller S, Mouridsen HT, Carstensen B, Palshof T, Trampisch HJ, Dalesio O, de Vries EG, Rodenhuis S, van Tinteren H, Comis RL, Davidson NE, Gray R, Robert N, Sledge G, Solin LJ, Sparano JA, Tormey DC, Wood W, Cameron D, Chetty U, Dixon JM, Forrest P, Jack W, Kunkler I, Rossbach J, Klijn JG, Treurniet-Donker AD, van Putten WL, Rotmensz N, Veronesi U, Viale G, Bartelink H, Bijker N, Bogaerts J, Cardoso F, Cufer T, Julien JP, Rutgers E, van de Velde CJ, Cunningham MP, Huovinen R, Joensuu H, Costa A, Tinterri C, Bonadonna G, Gianni L, Valagussa P, Goldstein LJ, Bonneterre J, Fargeot P, Fumoleau P, Kerbrat P, Luporsi E, Namer M, Eiermann W, Hilfrich J, Jonat W, Kaufmann M, Kreienberg R, Schumacher M, Bastert G, Rauschecker H, Sauer R, Sauerbrei W, Schauer A, Schumacher M, Blohmer JU, Costa SD, Eidtmann H, Gerber G, Jackisch C, Loibl S, von Minckwitz G, de Schryver A, Vakaet L, Belfiglio M, Nicolucci A, Pellegrini F, Pirozzoli MC, Sacco M, Valentini M, McArdle CS, Smith DC, Stallard S, Dent DM, Gudgeon CA, Hacking A, Murray E, Panieri E, Werner ID, Carrasco E, Martin M, Segui MA, Galligioni E, Lopez M, Erazo A, Medina JY, Horiguchi J, Takei H, Fentiman IS, Hayward JL, Rubens RD, Skilton D, Scheurlen H, Kaufmann M, Sohn HC, Untch M, Dafni U, Markopoulos C, Dafni D, Fountzilas G, Mavroudis D, Klefstrom P, Saarto T, Gallen M, Margreiter R, de Lafontan B, Mihura J, Roché H, Asselain B, Salmon RJ, Vilcoq JR, Arriagada R, Bourgier C, Hill C, Koscielny S, Laplanche A, Lê MG, Spielmann M, A'Hern R, Bliss J, Ellis P, Kilburn L, Yarnold JR, Benraadt J, Kooi M, van de Velde AO, van Dongen JA, Vermorken JB, Castiglione M, Coates A, Colleoni M, Collins J, Forbes J, Gelber RD, Goldhirsch A, Lindtner J, Price KN, Regan MM, Rudenstam CM, Senn HJ, Thuerlimann B, Bliss JM, Chilvers CE, Coombes RC, Hall E, Marty M, Buyse M, Possinger K, Schmid P, Untch M, Wallwiener D, Foster L, George WD, Stewart HJ, Stroner P, Borovik R, Hayat H, Inbar MJ, Robinson E, Bruzzi P, Del Mastro L, Pronzato P, Sertoli MR, Venturini M, Camerini T, De Palo G, Di Mauro MG, Formelli F, Valagussa P, Amadori D, Martoni A, Pannuti F, Camisa R, Cocconi G, Colozza A, Passalacqua R, Aogi K, Takashima S, Abe O, Ikeda T, Inokuchi K, Kikuchi K, Sawa K, Sonoo H, Korzeniowski S, Skolyszewski J, Ogawa M, Yamashita J, Bastiaannet E, van de Velde CJ, van de Water W, van Nes JG, Christiaens R, Neven P, Paridaens R, Van den Bogaert W, Braun S, Janni W, Martin P, Romain S, Janauer M, Seifert M, Sevelda P, Zielinski CC, Hakes T, Hudis CA, Norton L, Wittes R, Giokas G, Kondylis D, Lissaios B, de la Huerta R, Sainz MG, Altemus R, Camphausen K, Cowan K, Danforth D, Lichter A, Lippman M, O'Shaughnessy J, Pierce LJ, Steinberg S, Venzon D, Zujewski JA, D'Amico C, Lioce M, Paradiso A, Chapman JA, Gelmon K, Goss PE, Levine MN, Meyer R, Parulekar W, Pater JL, Pritchard KI, Shepherd LE, Tu D, Whelan T, Nomura Y, Ohno S, Anderson A, Bass G, Brown A, Bryant J, Costantino J, Dignam J, Fisher B, Geyer C, Mamounas EP, Paik S, Redmond C, Swain S, Wickerham L, Wolmark N, Baum M, Jackson IM, Palmer MK, Perez E, Ingle JN, Suman VJ, Bengtsson NO, Emdin S, Jonsson H, Del Mastro L, Venturini M, Lythgoe JP, Swindell R, Kissin M, Erikstein B, Hannisdal E, Jacobsen AB, Varhaug JE, Erikstein B, Gundersen S, Hauer-Jensen M, Høst H, Jacobsen AB, Nissen-Meyer R, Blamey RW, Mitchell AK, Morgan DA, Robertson JF, Ueo H, Di Palma M, Mathé G, Misset JL, Levine M, Pritchard KI, Whelan T, Morimoto K, Sawa K, Takatsuka Y, Crossley E, Harris A, Talbot D, Taylor M, Martin AL, Roché H, Cocconi G, di Blasio B, Ivanov V, Paltuev R, Semiglazov V, Brockschmidt J, Cooper MR, Falkson CI, A'Hern R, Ashley S, Dowsett M, Makris A, Powles TJ, Smith IE, Yarnold JR, Gazet JC, Browne L, Graham P, Corcoran N, Deshpande N, di Martino L, Douglas P, Hacking A, Høst H, Lindtner A, Notter G, Bryant AJ, Ewing GH, Firth LA, Krushen-Kosloski JL, Nissen-Meyer R, Anderson H, Killander F, Malmström P, Rydén L, Arnesson LG, Carstensen J, Dufmats M, Fohlin H, Nordenskjöld B, Söderberg M, Carpenter JT, Murray N, Royle GT, Simmonds PD, Albain K, Barlow W, Crowley J, Hayes D, Gralow J, Green S, Hortobagyi G, Livingston R, Martino S, Osborne CK, Adolfsson J, Bergh J, Bondesson T, Celebioglu F, Dahlberg K, Fornander T, Fredriksson I, Frisell J, Göransson E, Iiristo M, Johansson U, Lenner E, Löfgren L, Nikolaidis P, Perbeck L, Rotstein S, Sandelin K, Skoog L, Svane G, af Trampe E, Wadström C, Castiglione M, Goldhirsch A, Maibach R, Senn HJ, Thürlimann B, Hakama M, Holli K, Isola J, Rouhento K, Saaristo R, Brenner H, Hercbergs A, Martin AL, Roché H, Yoshimoto M, Paterson AH, Pritchard KI, Fyles A, Meakin JW, Panzarella T, Pritchard KI, Bahi J, Reid M, Spittle M, Bishop H, Bundred NJ, Cuzick J, Ellis IO, Fentiman IS, Forbes JF, Forsyth S, George WD, Pinder SE, Sestak I, Deutsch GP, Gray R, Kwong DL, Pai VR, Peto R, Senanayake F, Boccardo F, Rubagotti A, Baum M, Forsyth S, Hackshaw A, Houghton J, Ledermann J, Monson K, Tobias JS, Carlomagno C, De Laurentiis M, De Placido S, Williams L, Hayes D, Pierce LJ, Broglio K, Buzdar AU, Love RR, Ahlgren J, Garmo H, Holmberg L, Liljegren G, Lindman H, Wärnberg F, Asmar L, Jones SE, Gluz O, Harbeck N, Liedtke C, Nitz U, Litton A, Wallgren A, Karlsson P, Linderholm BK, Chlebowski RT, Caffier H.

Abstract

BACKGROUND:

After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.

METHODS:

We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.

FINDINGS:

Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7-17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6-6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2-17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8-5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20%), intermediate (10-19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1-12·5), 1·1% (-2·0 to 4·2), and 0·1% (-7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5-27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8-15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.

INTERPRETATION:

After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.