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. Funding Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.
Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials / Asselain, B; Barlow, W; Bartlett, J; Bergh, J; Bergsten-Nordstrom, E; Bliss, J; Boccardo, F; Boddington, C; Bogaerts, J; Bonadonna, G; Bradley, R; Brain, E; Braybrooke, J; Broet, P; Bryant, J; Burrett, J; Cameron, D; Clarke, M; Coates, A; Coleman, R; Coombes, R. C; Correa, C; Costantino, J; Cuzick, J; Danforth, D; Davidson, N; Davies, C; Davies, L; Di Leo, A; Dodwell, D; Dowsett, M; Duane, F; Evans, V; Ewertz, M; Fisher, B; Forbes, J; Ford, L; Gazet, J. -C; Gelber, R; Gettins, L; Gianni, L; Gnant, M; Godwin, J; Goldhirsch, A; Goodwin, P; Gray, R; Hayes, D; Hill, C; Ingle, J; Jagsi, R; Jakesz, R; James, S; Janni, W; Liu, H; Liu, Z; Lohrisch, C; Loibl, S; Mackinno, n. L.; Makris, A; Mamounas, E; Mannu, G; Martin, M; Mathoulin, S; Mauriac, L; Mcgale, P; Mchugh, T; Morris, P; Mukai, H; Norton, L; Ohashi, Y; Olivotto, I; Paik, S; Pan, H; Peto, R; Piccart, M; Pierce, L; Poortmans, P; Powles, T; Pritchard, K; Ragaz, J; Raina, V; Ravdin, P; Read, S; Regan, M; Robertson, J; Rutgers, E; Scholl, S; Slamon, D; Solkner, L; Sparano, J; Steinberg, S; Sutcliffe, R; Swain, S; Taylor, C; Tutt, A; Valagussa, P; van de Velde, C; van der Hage, J; Viale, G; von Minckwitz, G; Wang, Y; Wang, Z; Wang, X; Whelan, T; Wilcken, N; Winer, E; Wolmark, N; Wood, W; Zambetti, M; Zujewski, J. A; 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, (Yoshida; M., ).; Coles, Ce; Haybittle, Jl; Mobus, 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, Cfitzal; F, ; Fohler, H; Gnant, M; Greil, R; Jakesz, R; Marth, C; Mlineritsch, B; Pfeiler, G; Singer, Cf; Steger, Gg; Stoger, 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, Mb; 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, Ga; 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, Jh; 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, Lg; 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. - In: THE LANCET ONCOLOGY. - ISSN 1470-2045. - 19:1(2018), pp. 27-39. [10.1016/S1470-2045(17)30777-5]
Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials
Asselain, B; Barlow, W; Bartlett, J; Bergh, J; Bergsten-Nordstrom, E; Bliss, J; Boccardo, F; Boddington, C; Bogaerts, J; Bonadonna, G; Bradley, R; Brain, E; Braybrooke, J; Broet, P; Bryant, J; Burrett, J; Cameron, D; Clarke, M; Coates, A; Coleman, R; Coombes, R. C; Correa, C; Costantino, J; Cuzick, J; Danforth, D; Davidson, N; Davies, C; Davies, L; Di Leo, A; Dodwell, D; Dowsett, M; Duane, F; Evans, V; Ewertz, M; Fisher, B; Forbes, J; Ford, L; Gazet, J. -C; Gelber, R; Gettins, L; Gianni, L; Gnant, M; Godwin, J; Goldhirsch, A; Goodwin, P; Gray, R; Hayes, D; Hill, C; Ingle, J; Jagsi, R; Jakesz, R; James, S; Janni, W; Liu, H; Liu, Z; Lohrisch, C; Loibl, S; MacKinnon. L; Makris, A; Mamounas, E; Mannu, G; Martin, M; Mathoulin, S; Mauriac, L; McGale, P; McHugh, T; Morris, P; Mukai, H; Norton, L; Ohashi, Y; Olivotto, I; Paik, S; Pan, H; Peto, R; Piccart, M; Pierce, L; Poortmans, P; Powles, T; Pritchard, K; Ragaz, J; Raina, V; Ravdin, P; Read, S; Regan, M; Robertson, J; Rutgers, E; Scholl, S; Slamon, D; Solkner, L; Sparano, J; Steinberg, S; Sutcliffe, R; Swain, S; Taylor, C; Tutt, A; Valagussa, P; van de Velde, C; van der Hage, J; Viale, G; von Minckwitz, G; Wang, Y; Wang, Z; Wang, X; Whelan, T; Wilcken, N; Winer, E; Wolmark, N; Wood, W; Zambetti, M; Zujewski, J. A; 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 (Yoshida; M. ); Coles, CE; Haybittle, JL; Mobus, 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 CFitzal; F; Fohler, H; Gnant, M; Greil, R; Jakesz, R; Marth, C; Mlineritsch, B; Pfeiler, G; Singer, CF; Steger, GG; Stoger, 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, MB; 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, GA; 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, JH; 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, LG; 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
2018-01-01
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. Funding Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.
Citazione
Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials / Asselain, B; Barlow, W; Bartlett, J; Bergh, J; Bergsten-Nordstrom, E; Bliss, J; Boccardo, F; Boddington, C; Bogaerts, J; Bonadonna, G; Bradley, R; Brain, E; Braybrooke, J; Broet, P; Bryant, J; Burrett, J; Cameron, D; Clarke, M; Coates, A; Coleman, R; Coombes, R. C; Correa, C; Costantino, J; Cuzick, J; Danforth, D; Davidson, N; Davies, C; Davies, L; Di Leo, A; Dodwell, D; Dowsett, M; Duane, F; Evans, V; Ewertz, M; Fisher, B; Forbes, J; Ford, L; Gazet, J. -C; Gelber, R; Gettins, L; Gianni, L; Gnant, M; Godwin, J; Goldhirsch, A; Goodwin, P; Gray, R; Hayes, D; Hill, C; Ingle, J; Jagsi, R; Jakesz, R; James, S; Janni, W; Liu, H; Liu, Z; Lohrisch, C; Loibl, S; Mackinno, n. L.; Makris, A; Mamounas, E; Mannu, G; Martin, M; Mathoulin, S; Mauriac, L; Mcgale, P; Mchugh, T; Morris, P; Mukai, H; Norton, L; Ohashi, Y; Olivotto, I; Paik, S; Pan, H; Peto, R; Piccart, M; Pierce, L; Poortmans, P; Powles, T; Pritchard, K; Ragaz, J; Raina, V; Ravdin, P; Read, S; Regan, M; Robertson, J; Rutgers, E; Scholl, S; Slamon, D; Solkner, L; Sparano, J; Steinberg, S; Sutcliffe, R; Swain, S; Taylor, C; Tutt, A; Valagussa, P; van de Velde, C; van der Hage, J; Viale, G; von Minckwitz, G; Wang, Y; Wang, Z; Wang, X; Whelan, T; Wilcken, N; Winer, E; Wolmark, N; Wood, W; Zambetti, M; Zujewski, J. A; 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, (Yoshida; M., ).; Coles, Ce; Haybittle, Jl; Mobus, 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, Cfitzal; F, ; Fohler, H; Gnant, M; Greil, R; Jakesz, R; Marth, C; Mlineritsch, B; Pfeiler, G; Singer, Cf; Steger, Gg; Stoger, 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, Mb; 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, Ga; 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, Jh; 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, Lg; 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. - In: THE LANCET ONCOLOGY. - ISSN 1470-2045. - 19:1(2018), pp. 27-39. [10.1016/S1470-2045(17)30777-5]
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Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande. La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.