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Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

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Title: Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials
Authors: Alberro, JA
Ballester, B
Deulofeu, P
Fabregas, R
Fraile, M
Gubern, JM
Janer, J
Moral, A
De Pablo, JL
Penalva, G
Puig, P
Ramos, M
Rojo, R
Santesteban, P
Serra, C
Sola, M
Solarnau, L
Solsona, J
Veloso, E
Vidal, S
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
Coles, CE
Haybittle, JL
Moebus, V
Leonard, CF
Calais, G
Garaud, P
Collett, V
Davies, C
Delmestri, A
Sayer, J
Harvey, VJ
Holdaway, IM
Kay, RG
Mason, BH
Forbe, JF
Franci, PA
Wilcken, N
Balic, M
Bartsch, R
Fesl, C
Fitzal, F
Fohler, H
Gnant, M
Greil, R
Jakesz, R
Marth, C
Mlineritsch, B
Pfeiler, G
Singer, CF
Steger, GG
Stoeger, H
Canney, P
Yosef, HMA
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, PSGJ
Bates, T
Blamey, RW
Chetty, U
Ellis, IO
Mallon, E
Morgan, DAL
Patnick, J
Pinder, S
Lohrisch, C
Nichol, A
Bartlett, JMS
Bramwell, VH
Chen, BE
Chia, SKL
Gelmon, K
Goss, PE
Levine, MN
Parulekar, W
Pater, JL
Pritchard, KI
Shepherd, LE
Tu, D
Whelan, T
Berry, D
Broadwater, G
Cirrincione, C
Muss, H
Norton, L
Weiss, RB
Abu-Zahara, HT
Karpov, A
Portnoj, SL
Bowden, S
Brookes, C
Dunn, J
Fernando, I
Lee, M
Poole, C
Rea, D
Spooner, D
Barrett-Lee, PJ
Manse, RE
Monypenny, IJ
Gordon, NH
Davis, HL
Cuzick, J
Sestak, I
Lehingue, Y
Romestaing, P
Dubois, JB
Delozier, T
Griffon, B
Lesec'h, JM
Mustacchi, G
Petruzelka, L
Pribylova, O
Owen, JR
Meier, P
Shan, Y
Shao, YF
Wang, X
Zhao, DB
Howell, A
Swindell, R
Albano, J
De Oliveira, CF
Gervasio, H
Gordilho, J
Ejlertsen, B
Jensen, M-B
Mouridsen, H
Gelman, RS
Harris, JR
Hayes, D
Henderson, C
Shapiro, CL
Christiansen, P
Ejlertsen, B
Ewertz, M
Jensen, MB
Mouridsen, HT
Fehm, T
Trampisch, HJ
Dalesio, O
De Vries, EGE
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, JGM
Treurniet-Donker, AD
Van Putten, WLJ
Rotmensz, N
Veronesi, U
Viale, G
Bartelink, H
Bijker, N
Bogaerts, J
Cardoso, F
Cufer, T
Julien, JP
Poortmans, PM
Rutgers, E
Van de Velde, CJH
Cunningham, MP
Huovinen, R
Joensuu, H
Costa, A
Bonadonna, G
Gianni, L
Valagussa, P
Goldstein, LJ
Bonneterre, J
Fargeot, P
Fumoleau, P
Kerbrat, P
Lupors, E
Namer, M
Carrasco, E
Martin, M
Segui, MA
Eierman, 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, B
Jackisch, C
Loib, 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
De Salvo, GL
Del Bianco, P
Zavagno, G
Leone, B
Vallejo, CT
Zwenger, A
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
Bamia, C
Fountzilas, G
Koliou, G-A
Manousou, K
Mavroudis, D
Klefstrom, P
Blomqvist, C
Saarto, T
Gallen, M
Canavese, G
Tinterri, C
Margreiter, R
De Lafontan, B
Mihura, J
Roche, H
Asselain, B
Salmon, RJ
Vilcoq, JR
Brain, E
De La Lande, B
Mouret-Fourme, E
Andre, F
Arriagada, R
Delaloge, S
Hill, C
Koscienly, S
Michiels, S
Rubino, C
A'Hern, R
Bliss, J
Ellis, P
Kilburn, L
Yarnold, JR
Martin, M
Benraadt, J
Kooi, M
Van de Velde, AO
Van Dongen, JA
Vermorken, JB
Castiglione, M
Coates, A
Colleoni, M
Collins, J
Forbes, J
Gelbe, RD
Goldhirsch, A
Lindtner, J
Price, KN
Regan, MM
Rudenstam, CM
Senn, HJ
Thuerlimann, B
Bliss, JM
Chilvers, CED
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
Peretz, T
Robinson, E
Camerini, T
Formelli, F
Martelli, G
Di Mauro, MG
Valagussa, P
Perrone, F
Amadori, D
Martoni, A
Pannuti, F
Camisa, R
Musolino, A
Passalacqua, R
Iwata, H
Shien, T
Abe, O
Ikeda, T
Inokuchi, K
Kikuchi, K
Sawa, K
Sonoo, H
Sadoon, M
Tulusan, AH
Kohno, N
Miyashita, M
Takao, S
Ahn, J-H
Jung, KH
Korzeniowski, S
Skolyszewski, J
Ogawa, M
Yamashita, J
Bastiaannet, E
Liefers, GJ
Van de Velde, CJH
Christiaens, R
Neven, P
Paridaens, R
Van den Bogaert, W
Gazet, JC
Corcoran, N
Deshpande, N
Di Martino, L
Douglas, P
Hacking, A
Host, H
Lindtner, A
Notter, G
Bryant, AJS
Ewing, GH
Firth, LA
Krushen-Kosloski, JL
Nissen-Meyer, R
Anderson, H
Killander, F
Malmstrom, P
Ryden, L
Arnesson, L-G
Carstense, J
Dufmats, M
Fohlin, H
Nordenskjold, B
Soderberg, M
Sundqvist, M
Carpenter, TJ
Murray, N
Royle, GT
Simmonds, PD
Albain, K
Barlow, W
Crowley, J
Hayes, D
Gralow, J
Hortobagyi, G
Livingston, R
Martino, S
Osborne, CK
Ravdin, PM
Bergh, J
Bondesso, T
Celebiogl, F
Dahlberg, K
Fornander, T
Fredriksson, I
Frisell, J
Goransson, E
Iiristo, M
Johansson, U
Lenner, E
Lofgren, L
Nikolaidis, P
Perbeck, L
Rotstein, S
Sandelin, K
Skoog, L
Svane, G
Af Trampe, E
Wadstrom, C
Janni, W
Castiglione, M
Goldhirsch, A
Maibach, R
Senn, HJ
Thurlimann, B
Bartlett, JMS
Bastiaannet, E
Hadji, P
Hozumi, J
Rea, D
Van de Velde, CJH
Holli, K
Rouhento, K
Safra, T
Brenner, H
Hercbergs, A
Yoshimoto, M
Paterson, AHG
Pritchard, KI
Fyles, A
Meakin, JW
Panzarella, T
Pritchard, KI
Bahi, J
Delaloge, S
Lemonnier, J
Martin, AL
Reid, M
Spittle, M
Bishop, H
Bundred, NJ
Cuzick, J
Ellis, IO
Fentiman, IS
Forbes, JF
Forsyth, S
George, WS
Pinder, SE
Sestak, I
Deutsch, GP
Gray, R
Kwong, DLW
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
Schem, C
Williams, L
Bell, R
Cameron, D
Coleman, RE
Dodwell, D
Hinsley, S
Marshall, HC
Hayes, D
Pierce, LJ
Basso, SMM
Lumachi, F
Solomayer, E
Coleman, RE
Horsman, JM
Lester, J
Winter, MC
Buzdar, AU
Hsu, L
Love, RR
Ahlgren, J
Garmo, H
Holmberg, L
Lindman, H
Warnberg, F
Asmar, L
Jones, SE
Aft, R
Gluz, O
Harbeck, N
Liedtke, C
Nitz, U
Litton, A
Wallgren, A
Karlsson, P
Linderholm, BK
Chlebowski, RT
Caffier, H
Brufsky, AM
Coleman, RE
Llombart, HA
Item Type: Journal Article
Abstract: Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.
Issue Date: 1-Jan-2018
Date of Acceptance: 1-Dec-2017
URI: http://hdl.handle.net/10044/1/59931
DOI: https://dx.doi.org/10.1016/S1470-2045(17)30777-5
ISSN: 1470-2045
Publisher: ELSEVIER SCIENCE INC
Start Page: 27
End Page: 39
Journal / Book Title: LANCET ONCOLOGY
Volume: 19
Issue: 1
Copyright Statement: © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Cancer Research UK
Pfizer Limited
Funder's Grant Number: C37/A8434
PG281732/GA9001DP
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
STIMULATING FACTOR
THERAPY
METHOTREXATE
RADIOTHERAPY
RECURRENCE
SURVIVAL
SURGERY
RISK
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Online Publication Date: 2017-12-11
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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