Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials

O. Abe, R. Abe, K. Enomoto, K. Kikuchi, H. Koyama, H. Masuda, Y. Nomura, K. Sakai, K. Sugimachi, T. Tominaga, J. Uchino, M. Yoshida, J. L. Haybittle, C. Davies, V. J. Harvey, T. M. Holdaway, R. G. Kay, B. H. Mason, J. F. Forbes, N. WilckenM. Gnant, R. Jakesz, M. Ploner, H. M.A. Yosef, C. Focan, J. P. Lobelle, U. Peek, G. D. Oates, J. Powell, M. Durand, L. Mauriac, A. Di Leo, S. Dolci, M. J. Piccart, M. B. Masood, D. Parker, J. J. Price, P. S.G.J. Hupperets, S. Jackson, J. Ragaz, D. Berry, G. Broadwater, C. Cirrincione, H. Muss, L. Norton, R. B. Weiss, H. T. Abu-Zahra, S. M. Portnoj, M. Baum, J. Cuzick, J. Houghton, D. Riley, R. E. Mansel, N. H. Gordon, H. L. Davis, A. Beatrice, J. Mihura, A. Naja, Y. Lehingue, P. Romestaing, J. B. Dubois, T. Delozier, J. Mace Lesec'h, P. Rambert, L. Petruzelka, O. Pribylova, J. R. Owen, N. Harbeck, F. Jänicke, C. Meisner, P. Meier, A. Howell, G. C. Ribeiro, R. Swindell, J. Burrett, M. Clarke, R. Collins, S. Darby, C. Davies, P. Elphinstone, V. Evans, J. Godwin, R. Gray, C. Harwood, C. Hicks, D. Jackson, S. James, E. MacKinnon, P. McGale, T. McHugh, G. Mead, P. Morris, J. Oulds, R. Peto, C. Taylor, Y. Wang, J. Albano, C. F. De Oliveira, H. Gervásio, J. Gordilho, H. Johansen, H. T. Mouridsen, R. S. Gelman, J. R. Harris, I. C. Henderson, C. L. Shapiro, P. Christiansen, B. Ejlertsen, H. T. Mouridsen, S. Møller, M. Overgaard, B. Carstensen, T. Palshof, H. J. Trampisch, O. Dalesio, E. G.E. De Vries, S. Rodenhuis, H. Van Tinteren, R. L. Comis, N. E. Davidson, R. Gray, N. Robert, G. Sledge, D. C. Tormey, W. Wood, D. Cameron, U. Chetty, P. Forrest, W. Jack, J. Rossbach, J. G.M. Klijn, A. D. Treurniet-Donker, W. L.J. Van Putten, A. Costa, U. Veronesi, H. Bartelink, L. Duchateau, C. Legrand, R. Sylvester, J. A. Van Der Hage, C. J.H. Van De Velde, M. P. Cunningham, R. Catalano, R. H. Creech, J. Bonneterre, P. Fargeot, P. Fumoleau, P. Kerbrat, M. Namer, W. Jonat, M. Kaufmann, M. Schumacher, G. Von Minckwitz, G. Bastert, H. Rauschecker, R. Sauer, W. Sauerbrei, A. Schauer, M. Schumacher, A. De Schryver, L. Vakaet, M. Belfiglio, A. Nicolucci, F. Pellegrini, M. Sacco, M. Valentini, C. S. McArdle, D. C. Smith, E. Galligioni, F. Boccardo, A. Rubagotti, D. M. Dent, C. A. Gudgeon, A. Hacking, A. Erazo, J. Y. Medina, M. Izuo, Y. Morishita, H. Takei, I. S. Fentiman, J. L. Hayward, R. D. Rubens, D. Skilton, H. Scheurlen, M. Kaufmann, D. Von Fournier, U. Dafni, G. Fountzilas, P. Klefstrom, C. Blomqvist, T. Saarto, R. Margreiter, B. Asselain, R. J. Salmon, J. R. Vilcoq, R. Arriagada, C. Hill, A. Laplanche, M. G. Lê, M. Spielmann, P. Bruzzi, E. Montanaro, R. Rosso, M. R. Sertoli, M. Venturini, D. Amadori, J. Benraadt, M. Kooi, A. O. Van De Velde, J. A. Van Dongen, J. B. Vermorken, M. Castiglione, F. Cavalli, A. Coates, J. Collins, J. Forbes, R. D. Gelber, A. Goldhirsch, J. Lindtner, K. N. Price, C. M. Rudenstam, H. J. Senn, J. M. Bliss, C. E.D. Chilvers, R. C. Coombes, E. Hall, M. Marty, R. Borovik, G. Brufman, H. Hayat, E. Robinson, N. Wigler, G. Bonadonna, T. Camerini, G. De Palo, M. Del Vecchio, F. Formelli, P. Valagussa, A. Martoni, F. Pannuti, G. Cocconi, A. Colozza, R. Camisa, K. Aogi, S. Takashima, O. Abe, T. Ikeda, K. Inokuchi, K. Kikuchi, K. Sawa, H. Sonoo, S. Korzeniowski, J. Skolyszewski, M. Ogawa, J. Yamashita, J. Bonte, R. Christiaens, R. Paridaens, W. Van Den Bogaert, P. Martin, S. Romain, T. Hakes, C. A. Hudis, L. Norton, R. Wittes, G. Giokas, D. Kondylis, B. Lissaios, R. De La Huerta, M. G. Sainz, R. Altemus, K. Cowan, D. Danforth, A. Lichter, M. Lippman, J. O'Shaughnessy, L. J. Pierce, S. Steinberg, D. Venzon, J. A. Zujewski, A. Paradiso, M. De Lena, F. Schittulli, J. D. Myles, J. L. Pater, K. I. Pritchard, T. Whelan, Y. Nomura, S. Anderson, G. Bass, A. Brown, J. Bryant, J. Costantino, J. Dignam, B. Fisher, C. Redmond, S. Wieand, N. Wolmark, M. Baum, I. M. Jackson, M. K. Palmer, J. N. Ingle, V. J. Suman, N. O. Bengtsson, H. Jonsson, L. G. Larsson, J. P. Lythgoe, R. Swindell, M. Kissin, B. Erikstein, E. Hannisdal, A. B. Jacobsen, J. E. Varhaug, B. Erikstein, S. Gundersen, M. Hauer-Jensen, H. Høst, A. B. Jacobsen, R. Nissen-Meyer, R. W. Blamey, A. K. Mitchell, D. A.L. Morgan, J. F.R. Robertson, M. Di Palma, G. Mathé, J. L. Misset, R. M. Clark, M. Levine, K. I. Pritchard, T. Whelan, K. Morimoto, K. Sawa, Y. Takatsuka, E. Crossley, A. Harris, D. Talbot, M. Taylor, G. Cocconi, B. Di Blasio, V. Ivanov, V. Semiglazov, J. Brockschmidt, M. R. Cooper, H. Ueo, C. I. Falkson, R. A'Hern, S. Ashley, T. J. Powles, I. E. Smith, J. R. Yarnold, J. C. Gazet, N. Corcoran, N. Deshpande, L. Di Martino, P. Douglas, A. Hacking, H. Høst, A. Lindtner, G. Notter, A. J.S. Bryant, G. H. Ewing, L. A. Firth, J. L. Krushen-Kosloski, R. Nissen-Meyer, L. Foster, W. D. George, H. J. Stewart, P. Stroner, P. Malmström, T. R. Möller, S. Rydén, I. Tengrup, L. Tennvall-Nittby, J. Carstenssen, M. Dufmats, T. Hatschek, B. Nordenskjöld, M. Söderberg, J. T. Carpenter, K. Albain, J. Crowley, S. Green, S. Martino, C. K. Osborne, P. M. Ravdin, U. Glas, U. Johansson, L. E. Rutqvist, T. Singnomklao, A. Wallgren, M. Castiglione, A. Goldhirsch, R. Maibach, H. J. Senn, B. Thürlimann, H. Brenner, A. Hercbergs, M. Yoshimoto, G. DeBoer, A. H.G. Paterson, K. I. Pritchard, J. W. Meakin, T. Panzarella, K. I. Pritchard, Y. Shan, Y. F. Shao, X. Wang, D. B. Zhao, Z. M. Chen, H. C. Pan, J. Bahi, M. Reid, M. Spittle, G. P. Deutsch, F. Senanayake, D. L.W. Kwong, A. R. Bianco, C. Carlomagno, M. De Laurentiis, S. De Placido, A. U. Buzdar, T. Smith, J. Bergh, L. Holmberg, G. Liljegren, J. Nilsson, M. Seifert, P. Sevelda, C. C. Zielinsky, R. B. Buchanan, M. Cross, G. T. Royle, J. A. Dunn, R. K. Hills, M. Lee, J. M. Morrison, D. Spooner, A. Litton, R. T. Chlebowski, H. Caffier

Research output: Contribution to journalArticle

3334 Citations (Scopus)

Abstract

Background: In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods: Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17 000 women; >10%, 25 000 women). Findings: About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25 000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44.6% versus 49.5% (absolute reduction 5.0%, SE 0.8, 2p<0.00001). These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30.5% versus 35.9% (reduction 5.4%, SE 1.7, 2p=0.0002; overall mortality reduction 5.3%, SE 1.8, 2p=0.005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54.7% versus 60.1% (reduction 5.4%, SE 1.3, 2p=0.0002; overall mortality reduction 4.4%, SE 1.2, 2p=0.0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1.12, SE 0.04, 2p=0.001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004). Interpretation: In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Original languageEnglish (US)
Pages (from-to)2087-2106
Number of pages20
JournalLancet
Volume366
Issue number9503
DOIs
StatePublished - Dec 17 2005

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Radiotherapy
Breast Neoplasms
Recurrence
Survival
Mortality
Breast
Segmental Mastectomy
Mastectomy
Thoracic Wall
Therapeutics
Meta-Analysis
Cause of Death
Heart Diseases
Lung Neoplasms
Neoplasms
Heart Rate
Lymph Nodes
Incidence

ASJC Scopus subject areas

  • Medicine(all)

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Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival : An overview of the randomised trials. / Abe, O.; Abe, R.; Enomoto, K.; Kikuchi, K.; Koyama, H.; Masuda, H.; Nomura, Y.; Sakai, K.; Sugimachi, K.; Tominaga, T.; Uchino, J.; Yoshida, M.; Haybittle, J. L.; Davies, C.; Harvey, V. J.; Holdaway, T. M.; Kay, R. G.; Mason, B. H.; Forbes, J. F.; Wilcken, N.; Gnant, M.; Jakesz, R.; Ploner, M.; Yosef, H. M.A.; Focan, C.; Lobelle, J. P.; Peek, U.; Oates, G. D.; Powell, J.; Durand, M.; Mauriac, L.; Di Leo, A.; Dolci, S.; Piccart, M. J.; Masood, M. B.; Parker, D.; Price, J. J.; Hupperets, P. S.G.J.; Jackson, S.; Ragaz, J.; Berry, D.; Broadwater, G.; Cirrincione, C.; Muss, H.; Norton, L.; Weiss, R. B.; Abu-Zahra, H. T.; Portnoj, S. M.; Baum, M.; Cuzick, J.; Houghton, J.; Riley, D.; Mansel, R. E.; Gordon, N. H.; Davis, H. L.; Beatrice, A.; Mihura, J.; Naja, A.; Lehingue, Y.; Romestaing, P.; Dubois, J. B.; Delozier, T.; Mace Lesec'h, J.; Rambert, P.; Petruzelka, L.; Pribylova, O.; Owen, J. R.; Harbeck, N.; Jänicke, F.; Meisner, C.; Meier, P.; Howell, A.; Ribeiro, G. C.; Swindell, R.; Burrett, J.; Clarke, M.; Collins, R.; Darby, S.; Davies, C.; Elphinstone, P.; Evans, V.; Godwin, J.; Gray, R.; Harwood, C.; Hicks, C.; Jackson, D.; James, S.; MacKinnon, E.; McGale, P.; McHugh, T.; Mead, G.; Morris, P.; Oulds, J.; Peto, R.; Taylor, C.; Wang, Y.; Albano, J.; De Oliveira, C. F.; Gervásio, H.; Gordilho, J.; Johansen, H.; Mouridsen, H. T.; Gelman, R. S.; Harris, J. R.; Henderson, I. C.; Shapiro, C. L.; Christiansen, P.; Ejlertsen, B.; Mouridsen, H. T.; Møller, S.; Overgaard, M.; Carstensen, B.; Palshof, T.; Trampisch, H. J.; Dalesio, O.; De Vries, E. G.E.; Rodenhuis, S.; Van Tinteren, H.; Comis, R. L.; Davidson, N. E.; Gray, R.; Robert, N.; Sledge, G.; Tormey, D. C.; Wood, W.; Cameron, D.; Chetty, U.; Forrest, P.; Jack, W.; Rossbach, J.; Klijn, J. G.M.; Treurniet-Donker, A. D.; Van Putten, W. L.J.; Costa, A.; Veronesi, U.; Bartelink, H.; Duchateau, L.; Legrand, C.; Sylvester, R.; Van Der Hage, J. A.; Van De Velde, C. J.H.; Cunningham, M. P.; Catalano, R.; Creech, R. H.; Bonneterre, J.; Fargeot, P.; Fumoleau, P.; Kerbrat, P.; Namer, M.; Jonat, W.; Kaufmann, M.; Schumacher, M.; Von Minckwitz, G.; Bastert, G.; Rauschecker, H.; Sauer, R.; Sauerbrei, W.; Schauer, A.; Schumacher, M.; De Schryver, A.; Vakaet, L.; Belfiglio, M.; Nicolucci, A.; Pellegrini, F.; Sacco, M.; Valentini, M.; McArdle, C. S.; Smith, D. C.; Galligioni, E.; Boccardo, F.; Rubagotti, A.; Dent, D. M.; Gudgeon, C. A.; Hacking, A.; Erazo, A.; Medina, J. Y.; Izuo, M.; Morishita, Y.; Takei, H.; Fentiman, I. S.; Hayward, J. L.; Rubens, R. D.; Skilton, D.; Scheurlen, H.; Kaufmann, M.; Von Fournier, D.; Dafni, U.; Fountzilas, G.; Klefstrom, P.; Blomqvist, C.; Saarto, T.; Margreiter, R.; Asselain, B.; Salmon, R. J.; Vilcoq, J. R.; Arriagada, R.; Hill, C.; Laplanche, A.; Lê, M. G.; Spielmann, M.; Bruzzi, P.; Montanaro, E.; Rosso, R.; Sertoli, M. R.; Venturini, M.; Amadori, D.; Benraadt, J.; Kooi, M.; Van De Velde, A. O.; Van Dongen, J. A.; Vermorken, J. B.; Castiglione, M.; Cavalli, F.; Coates, A.; Collins, J.; Forbes, J.; Gelber, R. D.; Goldhirsch, A.; Lindtner, J.; Price, K. N.; Rudenstam, C. M.; Senn, H. J.; Bliss, J. M.; Chilvers, C. E.D.; Coombes, R. C.; Hall, E.; Marty, M.; Borovik, R.; Brufman, G.; Hayat, H.; Robinson, E.; Wigler, N.; Bonadonna, G.; Camerini, T.; De Palo, G.; Del Vecchio, M.; Formelli, F.; Valagussa, P.; Martoni, A.; Pannuti, F.; Cocconi, G.; Colozza, A.; Camisa, 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.; Bonte, J.; Christiaens, R.; Paridaens, R.; Van Den Bogaert, W.; Martin, P.; Romain, S.; Hakes, T.; Hudis, C. A.; Norton, L.; Wittes, R.; Giokas, G.; Kondylis, D.; Lissaios, B.; De La Huerta, R.; Sainz, M. G.; Altemus, R.; Cowan, K.; Danforth, D.; Lichter, A.; Lippman, M.; O'Shaughnessy, J.; Pierce, L. J.; Steinberg, S.; Venzon, D.; Zujewski, J. A.; Paradiso, A.; De Lena, M.; Schittulli, F.; Myles, J. D.; Pater, J. L.; Pritchard, K. I.; Whelan, T.; Nomura, Y.; Anderson, S.; Bass, G.; Brown, A.; Bryant, J.; Costantino, J.; Dignam, J.; Fisher, B.; Redmond, C.; Wieand, S.; Wolmark, N.; Baum, M.; Jackson, I. M.; Palmer, M. K.; Ingle, J. N.; Suman, V. J.; Bengtsson, N. O.; Jonsson, H.; Larsson, L. G.; Lythgoe, J. P.; Swindell, R.; Kissin, M.; Erikstein, B.; Hannisdal, E.; Jacobsen, A. B.; Varhaug, J. E.; Erikstein, B.; Gundersen, S.; Hauer-Jensen, M.; Høst, H.; Jacobsen, A. B.; Nissen-Meyer, R.; Blamey, R. W.; Mitchell, A. K.; Morgan, D. A.L.; Robertson, J. F.R.; Di Palma, M.; Mathé, G.; Misset, J. L.; Clark, R. M.; Levine, M.; Pritchard, K. I.; Whelan, T.; Morimoto, K.; Sawa, K.; Takatsuka, Y.; Crossley, E.; Harris, A.; Talbot, D.; Taylor, M.; Cocconi, G.; Di Blasio, B.; Ivanov, V.; Semiglazov, V.; Brockschmidt, J.; Cooper, M. R.; Ueo, H.; Falkson, C. I.; A'Hern, R.; Ashley, S.; Powles, T. J.; Smith, I. E.; Yarnold, J. R.; Gazet, J. C.; Corcoran, N.; Deshpande, N.; Di Martino, L.; Douglas, P.; Hacking, A.; Høst, H.; Lindtner, A.; Notter, G.; Bryant, A. J.S.; Ewing, G. H.; Firth, L. A.; Krushen-Kosloski, J. L.; Nissen-Meyer, R.; Foster, L.; George, W. D.; Stewart, H. J.; Stroner, P.; Malmström, P.; Möller, T. R.; Rydén, S.; Tengrup, I.; Tennvall-Nittby, L.; Carstenssen, J.; Dufmats, M.; Hatschek, T.; Nordenskjöld, B.; Söderberg, M.; Carpenter, J. T.; Albain, K.; Crowley, J.; Green, S.; Martino, S.; Osborne, C. K.; Ravdin, P. M.; Glas, U.; Johansson, U.; Rutqvist, L. E.; Singnomklao, T.; Wallgren, A.; Castiglione, M.; Goldhirsch, A.; Maibach, R.; Senn, H. J.; Thürlimann, B.; Brenner, H.; Hercbergs, A.; Yoshimoto, M.; DeBoer, G.; Paterson, A. H.G.; Pritchard, K. I.; Meakin, J. W.; Panzarella, T.; Pritchard, K. I.; Shan, Y.; Shao, Y. F.; Wang, X.; Zhao, D. B.; Chen, Z. M.; Pan, H. C.; Bahi, J.; Reid, M.; Spittle, M.; Deutsch, G. P.; Senanayake, F.; Kwong, D. L.W.; Bianco, A. R.; Carlomagno, C.; De Laurentiis, M.; De Placido, S.; Buzdar, A. U.; Smith, T.; Bergh, J.; Holmberg, L.; Liljegren, G.; Nilsson, J.; Seifert, M.; Sevelda, P.; Zielinsky, C. C.; Buchanan, R. B.; Cross, M.; Royle, G. T.; Dunn, J. A.; Hills, R. K.; Lee, M.; Morrison, J. M.; Spooner, D.; Litton, A.; Chlebowski, R. T.; Caffier, H.

In: Lancet, Vol. 366, No. 9503, 17.12.2005, p. 2087-2106.

Research output: Contribution to journalArticle

Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, JL, Davies, C, Harvey, VJ, Holdaway, TM, Kay, RG, Mason, BH, Forbes, JF, Wilcken, N, Gnant, M, Jakesz, R, Ploner, M, Yosef, HMA, Focan, C, Lobelle, JP, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Piccart, MJ, Masood, MB, Parker, D, Price, JJ, Hupperets, PSGJ, Jackson, S, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, RB, Abu-Zahra, HT, Portnoj, SM, Baum, M, Cuzick, J, Houghton, J, Riley, D, Mansel, RE, Gordon, NH, Davis, HL, Beatrice, A, Mihura, J, Naja, A, Lehingue, Y, Romestaing, P, Dubois, JB, Delozier, T, Mace Lesec'h, J, Rambert, P, Petruzelka, L, Pribylova, O, Owen, JR, Harbeck, N, Jänicke, F, Meisner, C, Meier, P, Howell, A, Ribeiro, GC, Swindell, R, Burrett, J, Clarke, M, Collins, R, Darby, S, Davies, C, Elphinstone, P, Evans, V, Godwin, J, Gray, R, Harwood, C, Hicks, C, Jackson, D, James, S, MacKinnon, E, McGale, P, McHugh, T, Mead, G, Morris, P, Oulds, J, Peto, R, Taylor, C, Wang, Y, Albano, J, De Oliveira, CF, Gervásio, H, Gordilho, J, Johansen, H, Mouridsen, HT, Gelman, RS, Harris, JR, Henderson, IC, Shapiro, CL, Christiansen, P, Ejlertsen, B, Mouridsen, HT, Møller, S, Overgaard, M, Carstensen, B, Palshof, T, Trampisch, HJ, Dalesio, O, De Vries, EGE, Rodenhuis, S, Van Tinteren, H, Comis, RL, Davidson, NE, Gray, R, Robert, N, Sledge, G, Tormey, DC, Wood, W, Cameron, D, Chetty, U, Forrest, P, Jack, W, Rossbach, J, Klijn, JGM, Treurniet-Donker, AD, Van Putten, WLJ, Costa, A, Veronesi, U, Bartelink, H, Duchateau, L, Legrand, C, Sylvester, R, Van Der Hage, JA, Van De Velde, CJH, Cunningham, MP, Catalano, R, Creech, RH, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Namer, M, Jonat, W, Kaufmann, M, Schumacher, M, Von Minckwitz, G, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Schumacher, M, De Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Sacco, M, Valentini, M, McArdle, CS, Smith, DC, Galligioni, E, Boccardo, F, Rubagotti, A, Dent, DM, Gudgeon, CA, Hacking, A, Erazo, A, Medina, JY, Izuo, M, Morishita, Y, Takei, H, Fentiman, IS, Hayward, JL, Rubens, RD, Skilton, D, Scheurlen, H, Kaufmann, M, Von Fournier, D, Dafni, U, Fountzilas, G, Klefstrom, P, Blomqvist, C, Saarto, T, Margreiter, R, Asselain, B, Salmon, RJ, Vilcoq, JR, Arriagada, R, Hill, C, Laplanche, A, Lê, MG, Spielmann, M, Bruzzi, P, Montanaro, E, Rosso, R, Sertoli, MR, Venturini, M, Amadori, D, Benraadt, J, Kooi, M, Van De Velde, AO, Van Dongen, JA, Vermorken, JB, Castiglione, M, Cavalli, F, Coates, A, Collins, J, Forbes, J, Gelber, RD, Goldhirsch, A, Lindtner, J, Price, KN, Rudenstam, CM, Senn, HJ, Bliss, JM, Chilvers, CED, Coombes, RC, Hall, E, Marty, M, Borovik, R, Brufman, G, Hayat, H, Robinson, E, Wigler, N, Bonadonna, G, Camerini, T, De Palo, G, Del Vecchio, M, Formelli, F, Valagussa, P, Martoni, A, Pannuti, F, Cocconi, G, Colozza, A, Camisa, 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, Bonte, J, Christiaens, R, Paridaens, R, Van Den Bogaert, W, Martin, P, Romain, S, Hakes, T, Hudis, CA, Norton, L, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, De La Huerta, R, Sainz, MG, Altemus, R, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, LJ, Steinberg, S, Venzon, D, Zujewski, JA, Paradiso, A, De Lena, M, Schittulli, F, Myles, JD, Pater, JL, Pritchard, KI, Whelan, T, Nomura, Y, Anderson, S, Bass, G, Brown, A, Bryant, J, Costantino, J, Dignam, J, Fisher, B, Redmond, C, Wieand, S, Wolmark, N, Baum, M, Jackson, IM, Palmer, MK, Ingle, JN, Suman, VJ, Bengtsson, NO, Jonsson, H, Larsson, LG, 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, DAL, Robertson, JFR, Di Palma, M, Mathé, G, Misset, JL, Clark, RM, Levine, M, Pritchard, KI, Whelan, T, Morimoto, K, Sawa, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Cocconi, G, Di Blasio, B, Ivanov, V, Semiglazov, V, Brockschmidt, J, Cooper, MR, Ueo, H, Falkson, CI, A'Hern, R, Ashley, S, Powles, TJ, Smith, IE, Yarnold, JR, Gazet, JC, Corcoran, N, Deshpande, N, Di Martino, L, Douglas, P, Hacking, A, Høst, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Firth, LA, Krushen-Kosloski, JL, Nissen-Meyer, R, Foster, L, George, WD, Stewart, HJ, Stroner, P, Malmström, P, Möller, TR, Rydén, S, Tengrup, I, Tennvall-Nittby, L, Carstenssen, J, Dufmats, M, Hatschek, T, Nordenskjöld, B, Söderberg, M, Carpenter, JT, Albain, K, Crowley, J, Green, S, Martino, S, Osborne, CK, Ravdin, PM, Glas, U, Johansson, U, Rutqvist, LE, Singnomklao, T, Wallgren, A, Castiglione, M, Goldhirsch, A, Maibach, R, Senn, HJ, Thürlimann, B, Brenner, H, Hercbergs, A, Yoshimoto, M, DeBoer, G, Paterson, AHG, Pritchard, KI, Meakin, JW, Panzarella, T, Pritchard, KI, Shan, Y, Shao, YF, Wang, X, Zhao, DB, Chen, ZM, Pan, HC, Bahi, J, Reid, M, Spittle, M, Deutsch, GP, Senanayake, F, Kwong, DLW, Bianco, AR, Carlomagno, C, De Laurentiis, M, De Placido, S, Buzdar, AU, Smith, T, Bergh, J, Holmberg, L, Liljegren, G, Nilsson, J, Seifert, M, Sevelda, P, Zielinsky, CC, Buchanan, RB, Cross, M, Royle, GT, Dunn, JA, Hills, RK, Lee, M, Morrison, JM, Spooner, D, Litton, A, Chlebowski, RT & Caffier, H 2005, 'Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials', Lancet, vol. 366, no. 9503, pp. 2087-2106. https://doi.org/10.1016/S0140-6736(05)67887-7
Abe, O. ; Abe, R. ; Enomoto, K. ; Kikuchi, K. ; Koyama, H. ; Masuda, H. ; Nomura, Y. ; Sakai, K. ; Sugimachi, K. ; Tominaga, T. ; Uchino, J. ; Yoshida, M. ; Haybittle, J. L. ; Davies, C. ; Harvey, V. J. ; Holdaway, T. M. ; Kay, R. G. ; Mason, B. H. ; Forbes, J. F. ; Wilcken, N. ; Gnant, M. ; Jakesz, R. ; Ploner, M. ; Yosef, H. M.A. ; Focan, C. ; Lobelle, J. P. ; Peek, U. ; Oates, G. D. ; Powell, J. ; Durand, M. ; Mauriac, L. ; Di Leo, A. ; Dolci, S. ; Piccart, M. J. ; Masood, M. B. ; Parker, D. ; Price, J. J. ; Hupperets, P. S.G.J. ; Jackson, S. ; Ragaz, J. ; Berry, D. ; Broadwater, G. ; Cirrincione, C. ; Muss, H. ; Norton, L. ; Weiss, R. B. ; Abu-Zahra, H. T. ; Portnoj, S. M. ; Baum, M. ; Cuzick, J. ; Houghton, J. ; Riley, D. ; Mansel, R. E. ; Gordon, N. H. ; Davis, H. L. ; Beatrice, A. ; Mihura, J. ; Naja, A. ; Lehingue, Y. ; Romestaing, P. ; Dubois, J. B. ; Delozier, T. ; Mace Lesec'h, J. ; Rambert, P. ; Petruzelka, L. ; Pribylova, O. ; Owen, J. R. ; Harbeck, N. ; Jänicke, F. ; Meisner, C. ; Meier, P. ; Howell, A. ; Ribeiro, G. C. ; Swindell, R. ; Burrett, J. ; Clarke, M. ; Collins, R. ; Darby, S. ; Davies, C. ; Elphinstone, P. ; Evans, V. ; Godwin, J. ; Gray, R. ; Harwood, C. ; Hicks, C. ; Jackson, D. ; James, S. ; MacKinnon, E. ; McGale, P. ; McHugh, T. ; Mead, G. ; Morris, P. ; Oulds, J. ; Peto, R. ; Taylor, C. ; Wang, Y. ; Albano, J. ; De Oliveira, C. F. ; Gervásio, H. ; Gordilho, J. ; Johansen, H. ; Mouridsen, H. T. ; Gelman, R. S. ; Harris, J. R. ; Henderson, I. C. ; Shapiro, C. L. ; Christiansen, P. ; Ejlertsen, B. ; Mouridsen, H. T. ; Møller, S. ; Overgaard, M. ; Carstensen, B. ; Palshof, T. ; Trampisch, H. J. ; Dalesio, O. ; De Vries, E. G.E. ; Rodenhuis, S. ; Van Tinteren, H. ; Comis, R. L. ; Davidson, N. E. ; Gray, R. ; Robert, N. ; Sledge, G. ; Tormey, D. C. ; Wood, W. ; Cameron, D. ; Chetty, U. ; Forrest, P. ; Jack, W. ; Rossbach, J. ; Klijn, J. G.M. ; Treurniet-Donker, A. D. ; Van Putten, W. L.J. ; Costa, A. ; Veronesi, U. ; Bartelink, H. ; Duchateau, L. ; Legrand, C. ; Sylvester, R. ; Van Der Hage, J. A. ; Van De Velde, C. J.H. ; Cunningham, M. P. ; Catalano, R. ; Creech, R. H. ; Bonneterre, J. ; Fargeot, P. ; Fumoleau, P. ; Kerbrat, P. ; Namer, M. ; Jonat, W. ; Kaufmann, M. ; Schumacher, M. ; Von Minckwitz, G. ; Bastert, G. ; Rauschecker, H. ; Sauer, R. ; Sauerbrei, W. ; Schauer, A. ; Schumacher, M. ; De Schryver, A. ; Vakaet, L. ; Belfiglio, M. ; Nicolucci, A. ; Pellegrini, F. ; Sacco, M. ; Valentini, M. ; McArdle, C. S. ; Smith, D. C. ; Galligioni, E. ; Boccardo, F. ; Rubagotti, A. ; Dent, D. M. ; Gudgeon, C. A. ; Hacking, A. ; Erazo, A. ; Medina, J. Y. ; Izuo, M. ; Morishita, Y. ; Takei, H. ; Fentiman, I. S. ; Hayward, J. L. ; Rubens, R. D. ; Skilton, D. ; Scheurlen, H. ; Kaufmann, M. ; Von Fournier, D. ; Dafni, U. ; Fountzilas, G. ; Klefstrom, P. ; Blomqvist, C. ; Saarto, T. ; Margreiter, R. ; Asselain, B. ; Salmon, R. J. ; Vilcoq, J. R. ; Arriagada, R. ; Hill, C. ; Laplanche, A. ; Lê, M. G. ; Spielmann, M. ; Bruzzi, P. ; Montanaro, E. ; Rosso, R. ; Sertoli, M. R. ; Venturini, M. ; Amadori, D. ; Benraadt, J. ; Kooi, M. ; Van De Velde, A. O. ; Van Dongen, J. A. ; Vermorken, J. B. ; Castiglione, M. ; Cavalli, F. ; Coates, A. ; Collins, J. ; Forbes, J. ; Gelber, R. D. ; Goldhirsch, A. ; Lindtner, J. ; Price, K. N. ; Rudenstam, C. M. ; Senn, H. J. ; Bliss, J. M. ; Chilvers, C. E.D. ; Coombes, R. C. ; Hall, E. ; Marty, M. ; Borovik, R. ; Brufman, G. ; Hayat, H. ; Robinson, E. ; Wigler, N. ; Bonadonna, G. ; Camerini, T. ; De Palo, G. ; Del Vecchio, M. ; Formelli, F. ; Valagussa, P. ; Martoni, A. ; Pannuti, F. ; Cocconi, G. ; Colozza, A. ; Camisa, 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. ; Bonte, J. ; Christiaens, R. ; Paridaens, R. ; Van Den Bogaert, W. ; Martin, P. ; Romain, S. ; Hakes, T. ; Hudis, C. A. ; Norton, L. ; Wittes, R. ; Giokas, G. ; Kondylis, D. ; Lissaios, B. ; De La Huerta, R. ; Sainz, M. G. ; Altemus, R. ; Cowan, K. ; Danforth, D. ; Lichter, A. ; Lippman, M. ; O'Shaughnessy, J. ; Pierce, L. J. ; Steinberg, S. ; Venzon, D. ; Zujewski, J. A. ; Paradiso, A. ; De Lena, M. ; Schittulli, F. ; Myles, J. D. ; Pater, J. L. ; Pritchard, K. I. ; Whelan, T. ; Nomura, Y. ; Anderson, S. ; Bass, G. ; Brown, A. ; Bryant, J. ; Costantino, J. ; Dignam, J. ; Fisher, B. ; Redmond, C. ; Wieand, S. ; Wolmark, N. ; Baum, M. ; Jackson, I. M. ; Palmer, M. K. ; Ingle, J. N. ; Suman, V. J. ; Bengtsson, N. O. ; Jonsson, H. ; Larsson, L. G. ; Lythgoe, J. P. ; Swindell, R. ; Kissin, M. ; Erikstein, B. ; Hannisdal, E. ; Jacobsen, A. B. ; Varhaug, J. E. ; Erikstein, B. ; Gundersen, S. ; Hauer-Jensen, M. ; Høst, H. ; Jacobsen, A. B. ; Nissen-Meyer, R. ; Blamey, R. W. ; Mitchell, A. K. ; Morgan, D. A.L. ; Robertson, J. F.R. ; Di Palma, M. ; Mathé, G. ; Misset, J. L. ; Clark, R. M. ; Levine, M. ; Pritchard, K. I. ; Whelan, T. ; Morimoto, K. ; Sawa, K. ; Takatsuka, Y. ; Crossley, E. ; Harris, A. ; Talbot, D. ; Taylor, M. ; Cocconi, G. ; Di Blasio, B. ; Ivanov, V. ; Semiglazov, V. ; Brockschmidt, J. ; Cooper, M. R. ; Ueo, H. ; Falkson, C. I. ; A'Hern, R. ; Ashley, S. ; Powles, T. J. ; Smith, I. E. ; Yarnold, J. R. ; Gazet, J. C. ; Corcoran, N. ; Deshpande, N. ; Di Martino, L. ; Douglas, P. ; Hacking, A. ; Høst, H. ; Lindtner, A. ; Notter, G. ; Bryant, A. J.S. ; Ewing, G. H. ; Firth, L. A. ; Krushen-Kosloski, J. L. ; Nissen-Meyer, R. ; Foster, L. ; George, W. D. ; Stewart, H. J. ; Stroner, P. ; Malmström, P. ; Möller, T. R. ; Rydén, S. ; Tengrup, I. ; Tennvall-Nittby, L. ; Carstenssen, J. ; Dufmats, M. ; Hatschek, T. ; Nordenskjöld, B. ; Söderberg, M. ; Carpenter, J. T. ; Albain, K. ; Crowley, J. ; Green, S. ; Martino, S. ; Osborne, C. K. ; Ravdin, P. M. ; Glas, U. ; Johansson, U. ; Rutqvist, L. E. ; Singnomklao, T. ; Wallgren, A. ; Castiglione, M. ; Goldhirsch, A. ; Maibach, R. ; Senn, H. J. ; Thürlimann, B. ; Brenner, H. ; Hercbergs, A. ; Yoshimoto, M. ; DeBoer, G. ; Paterson, A. H.G. ; Pritchard, K. I. ; Meakin, J. W. ; Panzarella, T. ; Pritchard, K. I. ; Shan, Y. ; Shao, Y. F. ; Wang, X. ; Zhao, D. B. ; Chen, Z. M. ; Pan, H. C. ; Bahi, J. ; Reid, M. ; Spittle, M. ; Deutsch, G. P. ; Senanayake, F. ; Kwong, D. L.W. ; Bianco, A. R. ; Carlomagno, C. ; De Laurentiis, M. ; De Placido, S. ; Buzdar, A. U. ; Smith, T. ; Bergh, J. ; Holmberg, L. ; Liljegren, G. ; Nilsson, J. ; Seifert, M. ; Sevelda, P. ; Zielinsky, C. C. ; Buchanan, R. B. ; Cross, M. ; Royle, G. T. ; Dunn, J. A. ; Hills, R. K. ; Lee, M. ; Morrison, J. M. ; Spooner, D. ; Litton, A. ; Chlebowski, R. T. ; Caffier, H. / Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival : An overview of the randomised trials. In: Lancet. 2005 ; Vol. 366, No. 9503. pp. 2087-2106.
@article{ee73bc9058394118b5e37094498ba6bf,
title = "Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials",
abstract = "Background: In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods: Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10{\%} (<10{\%}, 17 000 women; >10{\%}, 25 000 women). Findings: About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10{\%}) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25 000 women in the comparisons that involved substantial (>10{\%}) differences, however, 5-year local recurrence risks were 7{\%} active versus 26{\%} control (absolute reduction 19{\%}), and 15-year breast cancer mortality risks were 44.6{\%} versus 49.5{\%} (absolute reduction 5.0{\%}, SE 0.8, 2p<0.00001). These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7{\%} versus 26{\%} (reduction 19{\%}), and 15-year breast cancer mortality risks 30.5{\%} versus 35.9{\%} (reduction 5.4{\%}, SE 1.7, 2p=0.0002; overall mortality reduction 5.3{\%}, SE 1.8, 2p=0.005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6{\%} versus 23{\%} (reduction 17{\%}), and 15-year breast cancer mortality risks 54.7{\%} versus 60.1{\%} (reduction 5.4{\%}, SE 1.3, 2p=0.0002; overall mortality reduction 4.4{\%}, SE 1.2, 2p=0.0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1.12, SE 0.04, 2p=0.001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004). Interpretation: In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.",
author = "O. Abe and R. Abe and K. Enomoto and K. Kikuchi and H. Koyama and H. Masuda and Y. Nomura and K. Sakai and K. Sugimachi and T. Tominaga and J. Uchino and M. Yoshida and Haybittle, {J. L.} and C. Davies and Harvey, {V. J.} and Holdaway, {T. M.} and Kay, {R. G.} and Mason, {B. H.} and Forbes, {J. F.} and N. Wilcken and M. Gnant and R. Jakesz and M. Ploner and Yosef, {H. M.A.} and C. Focan and Lobelle, {J. P.} and U. Peek and Oates, {G. D.} and J. Powell and M. Durand and L. Mauriac and {Di Leo}, A. and S. Dolci and Piccart, {M. J.} and Masood, {M. B.} and D. Parker and Price, {J. J.} and Hupperets, {P. S.G.J.} and S. Jackson and J. Ragaz and D. Berry and G. Broadwater and C. Cirrincione and H. Muss and L. Norton and Weiss, {R. B.} and Abu-Zahra, {H. T.} and Portnoj, {S. M.} and M. Baum and J. Cuzick and J. Houghton and D. Riley and Mansel, {R. E.} and Gordon, {N. H.} and Davis, {H. L.} and A. Beatrice and J. Mihura and A. Naja and Y. Lehingue and P. Romestaing and Dubois, {J. B.} and T. Delozier and {Mace Lesec'h}, J. and P. Rambert and L. Petruzelka and O. Pribylova and Owen, {J. R.} and N. Harbeck and F. J{\"a}nicke and C. Meisner and P. Meier and A. Howell and Ribeiro, {G. C.} and R. Swindell and J. Burrett and M. Clarke and R. Collins and S. Darby and C. Davies and P. Elphinstone and V. Evans and J. Godwin and R. Gray and C. Harwood and C. Hicks and D. Jackson and S. James and E. MacKinnon and P. McGale and T. McHugh and G. Mead and P. Morris and J. Oulds and R. Peto and C. Taylor and Y. Wang and J. Albano and {De Oliveira}, {C. F.} and H. Gerv{\'a}sio and J. Gordilho and H. Johansen and Mouridsen, {H. T.} and Gelman, {R. S.} and Harris, {J. R.} and Henderson, {I. C.} and Shapiro, {C. L.} and P. Christiansen and B. Ejlertsen and Mouridsen, {H. T.} and S. M{\o}ller and M. Overgaard and B. Carstensen and T. Palshof and Trampisch, {H. J.} and O. Dalesio and {De Vries}, {E. G.E.} and S. Rodenhuis and {Van Tinteren}, H. and Comis, {R. L.} and Davidson, {N. E.} and R. Gray and N. Robert and G. Sledge and Tormey, {D. C.} and W. Wood and D. Cameron and U. Chetty and P. Forrest and W. Jack and J. Rossbach and Klijn, {J. G.M.} and Treurniet-Donker, {A. D.} and {Van Putten}, {W. L.J.} and A. Costa and U. Veronesi and H. Bartelink and L. Duchateau and C. Legrand and R. Sylvester and {Van Der Hage}, {J. A.} and {Van De Velde}, {C. J.H.} and Cunningham, {M. P.} and R. Catalano and Creech, {R. H.} and J. Bonneterre and P. Fargeot and P. Fumoleau and P. Kerbrat and M. Namer and W. Jonat and M. Kaufmann and M. Schumacher and {Von Minckwitz}, G. and G. Bastert and H. Rauschecker and R. Sauer and W. Sauerbrei and A. Schauer and M. Schumacher and {De Schryver}, A. and L. Vakaet and M. Belfiglio and A. Nicolucci and F. Pellegrini and M. Sacco and M. Valentini and McArdle, {C. S.} and Smith, {D. C.} and E. Galligioni and F. Boccardo and A. Rubagotti and Dent, {D. M.} and Gudgeon, {C. A.} and A. Hacking and A. Erazo and Medina, {J. Y.} and M. Izuo and Y. Morishita and H. Takei and Fentiman, {I. S.} and Hayward, {J. L.} and Rubens, {R. D.} and D. Skilton and H. Scheurlen and M. Kaufmann and {Von Fournier}, D. and U. Dafni and G. Fountzilas and P. Klefstrom and C. Blomqvist and T. Saarto and R. Margreiter and B. Asselain and Salmon, {R. J.} and Vilcoq, {J. R.} and R. Arriagada and C. Hill and A. Laplanche and L{\^e}, {M. G.} and M. Spielmann and P. Bruzzi and E. Montanaro and R. Rosso and Sertoli, {M. R.} and M. Venturini and D. Amadori and J. Benraadt and M. Kooi and {Van De Velde}, {A. O.} and {Van Dongen}, {J. A.} and Vermorken, {J. B.} and M. Castiglione and F. Cavalli and A. Coates and J. Collins and J. Forbes and Gelber, {R. D.} and A. Goldhirsch and J. Lindtner and Price, {K. N.} and Rudenstam, {C. M.} and Senn, {H. J.} and Bliss, {J. M.} and Chilvers, {C. E.D.} and Coombes, {R. C.} and E. Hall and M. Marty and R. Borovik and G. Brufman and H. Hayat and E. Robinson and N. Wigler and G. Bonadonna and T. Camerini and {De Palo}, G. and {Del Vecchio}, M. and F. Formelli and P. Valagussa and A. Martoni and F. Pannuti and G. Cocconi and A. Colozza and R. Camisa and K. Aogi and S. Takashima and O. Abe and T. Ikeda and K. Inokuchi and K. Kikuchi and K. Sawa and H. Sonoo and S. Korzeniowski and J. Skolyszewski and M. Ogawa and J. Yamashita and J. Bonte and R. Christiaens and R. Paridaens and {Van Den Bogaert}, W. and P. Martin and S. Romain and T. Hakes and Hudis, {C. A.} and L. Norton and R. Wittes and G. Giokas and D. Kondylis and B. Lissaios and {De La Huerta}, R. and Sainz, {M. G.} and R. Altemus and K. Cowan and D. Danforth and A. Lichter and M. Lippman and J. O'Shaughnessy and Pierce, {L. J.} and S. Steinberg and D. Venzon and Zujewski, {J. A.} and A. Paradiso and {De Lena}, M. and F. Schittulli and Myles, {J. D.} and Pater, {J. L.} and Pritchard, {K. I.} and T. Whelan and Y. Nomura and S. Anderson and G. Bass and A. Brown and J. Bryant and J. Costantino and J. Dignam and B. Fisher and C. Redmond and S. Wieand and N. Wolmark and M. Baum and Jackson, {I. M.} and Palmer, {M. K.} and Ingle, {J. N.} and Suman, {V. J.} and Bengtsson, {N. O.} and H. Jonsson and Larsson, {L. G.} and Lythgoe, {J. P.} and R. Swindell and M. Kissin and B. Erikstein and E. Hannisdal and Jacobsen, {A. B.} and Varhaug, {J. E.} and B. Erikstein and S. Gundersen and M. Hauer-Jensen and H. H{\o}st and Jacobsen, {A. B.} and R. Nissen-Meyer and Blamey, {R. W.} and Mitchell, {A. K.} and Morgan, {D. A.L.} and Robertson, {J. F.R.} and {Di Palma}, M. and G. Math{\'e} and Misset, {J. L.} and Clark, {R. M.} and M. Levine and Pritchard, {K. I.} and T. Whelan and K. Morimoto and K. Sawa and Y. Takatsuka and E. Crossley and A. Harris and D. Talbot and M. Taylor and G. Cocconi and {Di Blasio}, B. and V. Ivanov and V. Semiglazov and J. Brockschmidt and Cooper, {M. R.} and H. Ueo and Falkson, {C. I.} and R. A'Hern and S. Ashley and Powles, {T. J.} and Smith, {I. E.} and Yarnold, {J. R.} and Gazet, {J. C.} and N. Corcoran and N. Deshpande and {Di Martino}, L. and P. Douglas and A. Hacking and H. H{\o}st and A. Lindtner and G. Notter and Bryant, {A. J.S.} and Ewing, {G. H.} and Firth, {L. A.} and Krushen-Kosloski, {J. L.} and R. Nissen-Meyer and L. Foster and George, {W. D.} and Stewart, {H. J.} and P. Stroner and P. Malmstr{\"o}m and M{\"o}ller, {T. R.} and S. Ryd{\'e}n and I. Tengrup and L. Tennvall-Nittby and J. Carstenssen and M. Dufmats and T. Hatschek and B. Nordenskj{\"o}ld and M. S{\"o}derberg and Carpenter, {J. T.} and K. Albain and J. Crowley and S. Green and S. Martino and Osborne, {C. K.} and Ravdin, {P. M.} and U. Glas and U. Johansson and Rutqvist, {L. E.} and T. Singnomklao and A. Wallgren and M. Castiglione and A. Goldhirsch and R. Maibach and Senn, {H. J.} and B. Th{\"u}rlimann and H. Brenner and A. Hercbergs and M. Yoshimoto and G. DeBoer and Paterson, {A. H.G.} and Pritchard, {K. I.} and Meakin, {J. W.} and T. Panzarella and Pritchard, {K. I.} and Y. Shan and Shao, {Y. F.} and X. Wang and Zhao, {D. B.} and Chen, {Z. M.} and Pan, {H. C.} and J. Bahi and M. Reid and M. Spittle and Deutsch, {G. P.} and F. Senanayake and Kwong, {D. L.W.} and Bianco, {A. R.} and C. Carlomagno and {De Laurentiis}, M. and {De Placido}, S. and Buzdar, {A. U.} and T. Smith and J. Bergh and L. Holmberg and G. Liljegren and J. Nilsson and M. Seifert and P. Sevelda and Zielinsky, {C. C.} and Buchanan, {R. B.} and M. Cross and Royle, {G. T.} and Dunn, {J. A.} and Hills, {R. K.} and M. Lee and Morrison, {J. M.} and D. Spooner and A. Litton and Chlebowski, {R. T.} and H. Caffier",
year = "2005",
month = "12",
day = "17",
doi = "10.1016/S0140-6736(05)67887-7",
language = "English (US)",
volume = "366",
pages = "2087--2106",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9503",

}

TY - JOUR

T1 - Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival

T2 - An overview of the randomised trials

AU - Abe, O.

AU - Abe, R.

AU - Enomoto, K.

AU - Kikuchi, K.

AU - Koyama, H.

AU - Masuda, H.

AU - Nomura, Y.

AU - Sakai, K.

AU - Sugimachi, K.

AU - Tominaga, T.

AU - Uchino, J.

AU - Yoshida, M.

AU - Haybittle, J. L.

AU - Davies, C.

AU - Harvey, V. J.

AU - Holdaway, T. M.

AU - Kay, R. G.

AU - Mason, B. H.

AU - Forbes, J. F.

AU - Wilcken, N.

AU - Gnant, M.

AU - Jakesz, R.

AU - Ploner, M.

AU - Yosef, H. M.A.

AU - Focan, C.

AU - Lobelle, J. P.

AU - Peek, U.

AU - Oates, G. D.

AU - Powell, J.

AU - Durand, M.

AU - Mauriac, L.

AU - Di Leo, A.

AU - Dolci, S.

AU - Piccart, M. J.

AU - Masood, M. B.

AU - Parker, D.

AU - Price, J. J.

AU - Hupperets, P. S.G.J.

AU - Jackson, S.

AU - Ragaz, J.

AU - Berry, D.

AU - Broadwater, G.

AU - Cirrincione, C.

AU - Muss, H.

AU - Norton, L.

AU - Weiss, R. B.

AU - Abu-Zahra, H. T.

AU - Portnoj, S. M.

AU - Baum, M.

AU - Cuzick, J.

AU - Houghton, J.

AU - Riley, D.

AU - Mansel, R. E.

AU - Gordon, N. H.

AU - Davis, H. L.

AU - Beatrice, A.

AU - Mihura, J.

AU - Naja, A.

AU - Lehingue, Y.

AU - Romestaing, P.

AU - Dubois, J. B.

AU - Delozier, T.

AU - Mace Lesec'h, J.

AU - Rambert, P.

AU - Petruzelka, L.

AU - Pribylova, O.

AU - Owen, J. R.

AU - Harbeck, N.

AU - Jänicke, F.

AU - Meisner, C.

AU - Meier, P.

AU - Howell, A.

AU - Ribeiro, G. C.

AU - Swindell, R.

AU - Burrett, J.

AU - Clarke, M.

AU - Collins, R.

AU - Darby, S.

AU - Davies, C.

AU - Elphinstone, P.

AU - Evans, V.

AU - Godwin, J.

AU - Gray, R.

AU - Harwood, C.

AU - Hicks, C.

AU - Jackson, D.

AU - James, S.

AU - MacKinnon, E.

AU - McGale, P.

AU - McHugh, T.

AU - Mead, G.

AU - Morris, P.

AU - Oulds, J.

AU - Peto, R.

AU - Taylor, C.

AU - Wang, Y.

AU - Albano, J.

AU - De Oliveira, C. F.

AU - Gervásio, H.

AU - Gordilho, J.

AU - Johansen, H.

AU - Mouridsen, H. T.

AU - Gelman, R. S.

AU - Harris, J. R.

AU - Henderson, I. C.

AU - Shapiro, C. L.

AU - Christiansen, P.

AU - Ejlertsen, B.

AU - Mouridsen, H. T.

AU - Møller, S.

AU - Overgaard, M.

AU - Carstensen, B.

AU - Palshof, T.

AU - Trampisch, H. J.

AU - Dalesio, O.

AU - De Vries, E. G.E.

AU - Rodenhuis, S.

AU - Van Tinteren, H.

AU - Comis, R. L.

AU - Davidson, N. E.

AU - Gray, R.

AU - Robert, N.

AU - Sledge, G.

AU - Tormey, D. C.

AU - Wood, W.

AU - Cameron, D.

AU - Chetty, U.

AU - Forrest, P.

AU - Jack, W.

AU - Rossbach, J.

AU - Klijn, J. G.M.

AU - Treurniet-Donker, A. D.

AU - Van Putten, W. L.J.

AU - Costa, A.

AU - Veronesi, U.

AU - Bartelink, H.

AU - Duchateau, L.

AU - Legrand, C.

AU - Sylvester, R.

AU - Van Der Hage, J. A.

AU - Van De Velde, C. J.H.

AU - Cunningham, M. P.

AU - Catalano, R.

AU - Creech, R. H.

AU - Bonneterre, J.

AU - Fargeot, P.

AU - Fumoleau, P.

AU - Kerbrat, P.

AU - Namer, M.

AU - Jonat, W.

AU - Kaufmann, M.

AU - Schumacher, M.

AU - Von Minckwitz, G.

AU - Bastert, G.

AU - Rauschecker, H.

AU - Sauer, R.

AU - Sauerbrei, W.

AU - Schauer, A.

AU - Schumacher, M.

AU - De Schryver, A.

AU - Vakaet, L.

AU - Belfiglio, M.

AU - Nicolucci, A.

AU - Pellegrini, F.

AU - Sacco, M.

AU - Valentini, M.

AU - McArdle, C. S.

AU - Smith, D. C.

AU - Galligioni, E.

AU - Boccardo, F.

AU - Rubagotti, A.

AU - Dent, D. M.

AU - Gudgeon, C. A.

AU - Hacking, A.

AU - Erazo, A.

AU - Medina, J. Y.

AU - Izuo, M.

AU - Morishita, Y.

AU - Takei, H.

AU - Fentiman, I. S.

AU - Hayward, J. L.

AU - Rubens, R. D.

AU - Skilton, D.

AU - Scheurlen, H.

AU - Kaufmann, M.

AU - Von Fournier, D.

AU - Dafni, U.

AU - Fountzilas, G.

AU - Klefstrom, P.

AU - Blomqvist, C.

AU - Saarto, T.

AU - Margreiter, R.

AU - Asselain, B.

AU - Salmon, R. J.

AU - Vilcoq, J. R.

AU - Arriagada, R.

AU - Hill, C.

AU - Laplanche, A.

AU - Lê, M. G.

AU - Spielmann, M.

AU - Bruzzi, P.

AU - Montanaro, E.

AU - Rosso, R.

AU - Sertoli, M. R.

AU - Venturini, M.

AU - Amadori, D.

AU - Benraadt, J.

AU - Kooi, M.

AU - Van De Velde, A. O.

AU - Van Dongen, J. A.

AU - Vermorken, J. B.

AU - Castiglione, M.

AU - Cavalli, F.

AU - Coates, A.

AU - Collins, J.

AU - Forbes, J.

AU - Gelber, R. D.

AU - Goldhirsch, A.

AU - Lindtner, J.

AU - Price, K. N.

AU - Rudenstam, C. M.

AU - Senn, H. J.

AU - Bliss, J. M.

AU - Chilvers, C. E.D.

AU - Coombes, R. C.

AU - Hall, E.

AU - Marty, M.

AU - Borovik, R.

AU - Brufman, G.

AU - Hayat, H.

AU - Robinson, E.

AU - Wigler, N.

AU - Bonadonna, G.

AU - Camerini, T.

AU - De Palo, G.

AU - Del Vecchio, M.

AU - Formelli, F.

AU - Valagussa, P.

AU - Martoni, A.

AU - Pannuti, F.

AU - Cocconi, G.

AU - Colozza, A.

AU - Camisa, R.

AU - Aogi, K.

AU - Takashima, S.

AU - Abe, O.

AU - Ikeda, T.

AU - Inokuchi, K.

AU - Kikuchi, K.

AU - Sawa, K.

AU - Sonoo, H.

AU - Korzeniowski, S.

AU - Skolyszewski, J.

AU - Ogawa, M.

AU - Yamashita, J.

AU - Bonte, J.

AU - Christiaens, R.

AU - Paridaens, R.

AU - Van Den Bogaert, W.

AU - Martin, P.

AU - Romain, S.

AU - Hakes, T.

AU - Hudis, C. A.

AU - Norton, L.

AU - Wittes, R.

AU - Giokas, G.

AU - Kondylis, D.

AU - Lissaios, B.

AU - De La Huerta, R.

AU - Sainz, M. G.

AU - Altemus, R.

AU - Cowan, K.

AU - Danforth, D.

AU - Lichter, A.

AU - Lippman, M.

AU - O'Shaughnessy, J.

AU - Pierce, L. J.

AU - Steinberg, S.

AU - Venzon, D.

AU - Zujewski, J. A.

AU - Paradiso, A.

AU - De Lena, M.

AU - Schittulli, F.

AU - Myles, J. D.

AU - Pater, J. L.

AU - Pritchard, K. I.

AU - Whelan, T.

AU - Nomura, Y.

AU - Anderson, S.

AU - Bass, G.

AU - Brown, A.

AU - Bryant, J.

AU - Costantino, J.

AU - Dignam, J.

AU - Fisher, B.

AU - Redmond, C.

AU - Wieand, S.

AU - Wolmark, N.

AU - Baum, M.

AU - Jackson, I. M.

AU - Palmer, M. K.

AU - Ingle, J. N.

AU - Suman, V. J.

AU - Bengtsson, N. O.

AU - Jonsson, H.

AU - Larsson, L. G.

AU - Lythgoe, J. P.

AU - Swindell, R.

AU - Kissin, M.

AU - Erikstein, B.

AU - Hannisdal, E.

AU - Jacobsen, A. B.

AU - Varhaug, J. E.

AU - Erikstein, B.

AU - Gundersen, S.

AU - Hauer-Jensen, M.

AU - Høst, H.

AU - Jacobsen, A. B.

AU - Nissen-Meyer, R.

AU - Blamey, R. W.

AU - Mitchell, A. K.

AU - Morgan, D. A.L.

AU - Robertson, J. F.R.

AU - Di Palma, M.

AU - Mathé, G.

AU - Misset, J. L.

AU - Clark, R. M.

AU - Levine, M.

AU - Pritchard, K. I.

AU - Whelan, T.

AU - Morimoto, K.

AU - Sawa, K.

AU - Takatsuka, Y.

AU - Crossley, E.

AU - Harris, A.

AU - Talbot, D.

AU - Taylor, M.

AU - Cocconi, G.

AU - Di Blasio, B.

AU - Ivanov, V.

AU - Semiglazov, V.

AU - Brockschmidt, J.

AU - Cooper, M. R.

AU - Ueo, H.

AU - Falkson, C. I.

AU - A'Hern, R.

AU - Ashley, S.

AU - Powles, T. J.

AU - Smith, I. E.

AU - Yarnold, J. R.

AU - Gazet, J. C.

AU - Corcoran, N.

AU - Deshpande, N.

AU - Di Martino, L.

AU - Douglas, P.

AU - Hacking, A.

AU - Høst, H.

AU - Lindtner, A.

AU - Notter, G.

AU - Bryant, A. J.S.

AU - Ewing, G. H.

AU - Firth, L. A.

AU - Krushen-Kosloski, J. L.

AU - Nissen-Meyer, R.

AU - Foster, L.

AU - George, W. D.

AU - Stewart, H. J.

AU - Stroner, P.

AU - Malmström, P.

AU - Möller, T. R.

AU - Rydén, S.

AU - Tengrup, I.

AU - Tennvall-Nittby, L.

AU - Carstenssen, J.

AU - Dufmats, M.

AU - Hatschek, T.

AU - Nordenskjöld, B.

AU - Söderberg, M.

AU - Carpenter, J. T.

AU - Albain, K.

AU - Crowley, J.

AU - Green, S.

AU - Martino, S.

AU - Osborne, C. K.

AU - Ravdin, P. M.

AU - Glas, U.

AU - Johansson, U.

AU - Rutqvist, L. E.

AU - Singnomklao, T.

AU - Wallgren, A.

AU - Castiglione, M.

AU - Goldhirsch, A.

AU - Maibach, R.

AU - Senn, H. J.

AU - Thürlimann, B.

AU - Brenner, H.

AU - Hercbergs, A.

AU - Yoshimoto, M.

AU - DeBoer, G.

AU - Paterson, A. H.G.

AU - Pritchard, K. I.

AU - Meakin, J. W.

AU - Panzarella, T.

AU - Pritchard, K. I.

AU - Shan, Y.

AU - Shao, Y. F.

AU - Wang, X.

AU - Zhao, D. B.

AU - Chen, Z. M.

AU - Pan, H. C.

AU - Bahi, J.

AU - Reid, M.

AU - Spittle, M.

AU - Deutsch, G. P.

AU - Senanayake, F.

AU - Kwong, D. L.W.

AU - Bianco, A. R.

AU - Carlomagno, C.

AU - De Laurentiis, M.

AU - De Placido, S.

AU - Buzdar, A. U.

AU - Smith, T.

AU - Bergh, J.

AU - Holmberg, L.

AU - Liljegren, G.

AU - Nilsson, J.

AU - Seifert, M.

AU - Sevelda, P.

AU - Zielinsky, C. C.

AU - Buchanan, R. B.

AU - Cross, M.

AU - Royle, G. T.

AU - Dunn, J. A.

AU - Hills, R. K.

AU - Lee, M.

AU - Morrison, J. M.

AU - Spooner, D.

AU - Litton, A.

AU - Chlebowski, R. T.

AU - Caffier, H.

PY - 2005/12/17

Y1 - 2005/12/17

N2 - Background: In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods: Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17 000 women; >10%, 25 000 women). Findings: About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25 000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44.6% versus 49.5% (absolute reduction 5.0%, SE 0.8, 2p<0.00001). These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30.5% versus 35.9% (reduction 5.4%, SE 1.7, 2p=0.0002; overall mortality reduction 5.3%, SE 1.8, 2p=0.005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54.7% versus 60.1% (reduction 5.4%, SE 1.3, 2p=0.0002; overall mortality reduction 4.4%, SE 1.2, 2p=0.0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1.12, SE 0.04, 2p=0.001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004). Interpretation: In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

AB - Background: In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods: Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17 000 women; >10%, 25 000 women). Findings: About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25 000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44.6% versus 49.5% (absolute reduction 5.0%, SE 0.8, 2p<0.00001). These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30.5% versus 35.9% (reduction 5.4%, SE 1.7, 2p=0.0002; overall mortality reduction 5.3%, SE 1.8, 2p=0.005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54.7% versus 60.1% (reduction 5.4%, SE 1.3, 2p=0.0002; overall mortality reduction 4.4%, SE 1.2, 2p=0.0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1.12, SE 0.04, 2p=0.001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004). Interpretation: In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

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U2 - 10.1016/S0140-6736(05)67887-7

DO - 10.1016/S0140-6736(05)67887-7

M3 - Article

C2 - 16360786

AN - SCOPUS:29144475553

VL - 366

SP - 2087

EP - 2106

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9503

ER -