Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials Journal Article


Authors: Abe, O.; Abe, R.; Enomoto, K.; Kikuchi, K.; Koyama, H.; Masuda, H.; Nomura, Y.; Ohashi, Y.; Sakai, K.; Sugimachi, K.; Toi, M.; Tominaga, T.; Uchino, J.; Yoshida, M.; Haybittle, J. L.; Leonard, C. F.; Calais, G.; Geraud, P.; Collett, V.; Davies, C.; Delmestri, A.; Sayer, J.; Harvey, V. J.; Holdaway, I. M.; Kay, R. G.; Mason, B. H.; Forbes, J. F.; Wilcken, N.; Bartsch, R.; Dubsky, P.; Fesl, C.; Fohler, H.; Gnant, M.; Greil, R.; Jakesz, R.; Lang, A.; Luschin-Ebengreuth, G.; Marth, C.; Mlineritsch, B.; Samonigg, H.; Singer, C. F.; Steger, G. G.; Stöger, H.; Canney, P.; Yosef, H. M. A.; Focan, C.; Peek, U.; Oates, G. D.; Powell, J.; Durand, M.; Mauriac, L.; Di Leo, A.; Dolci, S.; Larsimont, D.; Nogaret, J. M.; Philippson, C.; Piccart, M. J.; Masood, M. B.; Parker, D.; Price, J. J.; Lindsay, M. A.; Mackey, J.; Martin, M.; Hupperets, P. S. G. J.; Bates, T.; Blamey, R. W.; Chetty, U.; Ellis, I. O.; Mallon, E.; Morgan, D. A. L.; Patnick, J.; Pinder, S.; Olivotto, I.; Ragaz, J.; Berry, D.; Broadwater, G.; Cirrincione, C.; Muss, H.; Norton, L.; Weiss, R. B.; Abu-Zahra, H. T.; Portnoj, S. M.; Bowden, S.; Brookes, C.; Dunn, J.; Fernando, I.; Lee, M.; Poole, C.; Rea, D.; Spooner, D.; Barrett-Lee, P. J.; Mansel, R. E.; Monypenny, I. J.; Gordon, N. H.; Davis, H. L.; Cuzick, J.; Lehingue, Y.; Romestaing, P.; Dubois, J. B.; Delozier, T.; Griffon, B.; Mace Lesec'h, J.; Rambert, P.; Mustacchi, G.; Petruzelka, L.; Pribylova, O.; Owen, J. R.; Harbeck, N.; Jänicke, F.; Meisner, C.; Schmitt, M.; Thomssen, C.; Meier, P.; Shan, Y.; Shao, Y. F.; Wang, X.; Zhao, D. B.; Chen, Z. M.; Pan, H. C.; Howell, A.; Swindell, R.; Burrett, J. A.; Clarke, M.; Collins, R.; Correa, C.; Cutter, D.; Darby, S.; Davies, C.; Davies, K.; Delmestri, A.; Elphinstone, P.; Evans, V.; Gettins, L.; Godwin, J.; Gray, R.; Gregory, C.; Hermans, D.; Hicks, C.; James, S.; Kerr, A.; MacKinnon, E.; Lay, M.; McGale, P.; McHugh, T.; Peto, R.; Sayer, J.; 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.; Hayes, D.; Henderson, C.; Shapiro, C. L.; Winer, E.; Christiansen, P.; Ejlertsen, B.; Ewertz, M.; Jensen, M. B.; Møller, S.; Mouridsen, H. T.; 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.; Solin, L. J.; Sparano, J. A.; Tormey, D. C.; Wood, W.; Cameron, D.; Chetty, U.; Dixon, J. M.; Forrest, P.; Jack, W.; Kunkler, I.; Rossbach, J.; Klijn, J. G. M.; Treurniet-Donker, A. D.; Van Putten, W. L. J.; Rotmensz, N.; Veronesi, U.; Viale, G.; Bartelink, H.; Bijker, N.; Bogaerts, J.; Cardoso, F.; Cufer, T.; Julien, J. P.; Rutgers, E.; Van De Velde, C. J. H.; Cunningham, M. P.; Huovinen, R.; Joensuu, H.; Costa, A.; Tinterri, C.; Bonadonna, G.; Gianni, L.; Valagussa, P.; Goldstein, L. J.; Bonneterre, J.; Fargeot, P.; Fumoleau, P.; Kerbrat, P.; Luporsi, E.; Namer, M.; Eiermann, W.; Hilfrich, J.; Jonat, W.; Kaufmann, M.; Kreienberg, R.; Schumacher, M.; Bastert, G.; Rauschecker, H.; Sauer, R.; Sauerbrei, W.; Schauer, A.; Schumacher, M.; Blohmer, J. U.; Costa, S. D.; Eidtmann, H.; Gerber, B.; Jackisch, C.; Loibl, S.; Von Minckwitz, G.; De Schryver, A.; Vakaet, L.; Belfiglio, M.; Nicolucci, A.; Pellegrini, F.; Pirozzoli, M. C.; Sacco, M.; Valentini, M.; McArdle, C. S.; Smith, D. C.; Stallard, S.; Dent, D. M.; Gudgeon, C. A.; Hacking, A.; Murray, E.; Panieri, E.; Werner, I. D.; Carrasco, E.; Martin, M.; Segui, M. A.; Galligioni, E.; Lopez, M.; Erazo, A.; Medina, J. Y.; Horiguchi, J.; Takei, H.; Fentiman, I. S.; Hayward, J. L.; Rubens, R. D.; Skilton, D.; Scheurlen, H.; Kaufmann, M.; Sohn, H. C.; Untch, M.; Dafni, U.; Markopoulos, C.; Dafni, U.; Fountzilas, G.; Mavroudis, D.; Klefstrom, P.; Blomqvist, C.; Saarto, T.; Gallen, M.; Margreiter, R.; De Lafontan, B.; Mihura, J.; Roché, H.; Asselain, B.; Salmon, R. J.; Vilcoq, J. R.; Arriagada, R.; Bourgier, C.; Hill, C.; Koscielny, S.; Laplanche, A.; Lê, M. G.; Spielmann, M.; A'Hern, R.; Bliss, J.; Ellis, P.; Kilburn, L.; Yarnold, J. R.; Benraadt, J.; Kooi, M.; Van De Velde, A. O.; Van Dongen, J. A.; Vermorken, J. B.; Castiglione, M.; Coates, A.; Colleoni, M.; Collins, J.; Forbes, J.; Gelber, R. D.; Goldhirsch, A.; Lindtner, J.; Price, K. N.; Regan, M. M.; Rudenstam, C. M.; Senn, H. J.; Thuerlimann, B.; Bliss, J. M.; Chilvers, C. E. D.; Coombes, R. C.; Hall, E.; Marty, M.; Buyse, M.; Possinger, K.; Schmid, P.; Wallwiener, D.; Foster, L.; George, W. D.; Stewart, H. J.; Stroner, P.; Borovik, R.; Hayat, H.; Inbar, M. J.; Robinson, E.; Bruzzi, P.; Del Mastro, L.; Pronzato, P.; Sertoli, M. R.; Venturini, M.; Camerini, T.; De Palo, G.; Di Mauro, M. G.; Formelli, F.; Valagussa, P.; Amadori, D.; Martoni, A.; Pannuti, F.; Camisa, R.; Cocconi, G.; Colozza, A.; Passalacqua, R.; Aogi, K.; Takashima, S.; Abe, O.; Ikeda, T.; Inokuchi, K.; Kikuchi, K.; Sawa, K.; Sonoo, H.; Korzeniowski, S.; Skolyszewski, J.; Ogawa, M.; Yamashita, J.; Bastiaannet, E.; Van De Velde, C. J. H.; Van De Water, W.; Van Nes, J. G. H.; Christiaens, R.; Neven, P.; Paridaens, R.; Van Den Bogaert, W.; Braun, S.; Janni, W.; Martin, P.; Romain, S.; Janauer, M.; Seifert, M.; Sevelda, P.; Zielinski, C. C.; Hakes, T.; Hudis, C. A.; Norton, L.; Wittes, R.; Giokas, G.; Kondylis, D.; Lissaios, B.; De La Huerta, R.; Sainz, M. G.; Altemus, R.; Camphausen, K.; Cowan, K.; Danforth, D.; Lichter, A.; Lippman, M.; O'Shaughnessy, J.; Pierce, L. J.; Steinberg, S.; Venzon, D.; Zujewski, J. A.; D'Amico, C.; Lioce, M.; Paradiso, A.; Chapman, J. A. W.; Gelmon, K.; Goss, P. E.; Levine, M. N.; Meyer, R.; Parulekar, W.; Pater, J. L.; Pritchard, K. I.; Shepherd, L. E.; Tu, D.; Whelan, T.; Nomura, Y.; Ohno, S.; Anderson, S.; Bass, G.; Brown, A.; Bryant, J.; Costantino, J.; Dignam, J.; Fisher, B.; Geyer, C.; Mamounas, E. P.; Paik, S.; Redmond, C.; Swain, S.; Wickerham, L.; Wolmark, N.; Baum, M.; Jackson, I. M.; Palmer, M. K.; Perez, E.; Ingle, J. N.; Suman, V. J.; Bengtsson, N. O.; Emdin, S.; Jonsson, H.; DiMast, Y.; Venturini, M.; Lythgoe, J. P.; 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.; Ueo, H.; Di Palma, M.; Mathé, G.; Misset, J. L.; Levine, M.; Pritchard, K. I.; Morimoto, K.; Sawa, K.; Takatsuka, Y.; Crossley, E.; Harris, A.; Talbot, D.; Taylor, M.; Martin, A. L.; Roché, H.; Cocconi, G.; Di Blasio, B.; Ivanov, V.; Paltuev, R.; Semiglazov, V.; Brockschmidt, J.; Cooper, M. R.; Falkson, C. I.; A'Hern, R.; Ashley, S.; Dowsett, M.; Makris, A.; Powles, T. J.; Smith, I. E.; Yarnold, J. R.; Gazet, J. C.; Browne, L.; Graham, P.; 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.; Anderson, H.; Killander, F.; Malmström, P.; Rydén, L.; Arnesson, L. G.; Carstensen, J.; Dufmats, M.; Fohlin, H.; Nordenskjöld, B.; Söderberg, M.; Carpenter, T. J.; Murray, N.; Royle, G. T.; Simmonds, P. D.; Albain, K.; Barlow, W.; Crowley, J.; Hayes, D.; Gralow, J.; Green, S.; Hortobagyi, G.; Livingston, R.; Martino, S.; Osborne, C. K.; Ravdin, P. M.; Adolfsson, J.; Bergh, J.; Bondesson, T.; Celebioglu, F.; Dahlberg, K.; Fornander, T.; Fredriksson, I.; Frisell, J.; Göransson, E.; Iiristo, M.; Johansson, U.; Lenner, E.; Löfgren, L.; Nikolaidis, P.; Perbeck, L.; Rotstein, S.; Sandelin, K.; Skoog, L.; Svane, G.; Af Trampe, E.; Wadström, C.; Castiglione, M.; Maibach, R.; Senn, H. J.; Thürlimann, B.; Hakama, M.; Holli, K.; Isola, J.; Rouhento, K.; Saaristo, R.; Brenner, H.; Hercbergs, A.; Martin, A. L.; Roché, H.; Yoshimoto, M.; Paterson, A. H. G.; Pritchard, K. I.; Fyles, A.; Meakin, J. W.; Panzarella, T.; Pritchard, K. I.; Bahi, J.; Reid, M.; Spittle, M.; Bishop, H.; Bundred, N. J.; Ellis, I. O.; Fentiman, I. S.; Forsyth, S.; George, W. D.; Pinder, S. E.; Sestak, I.; Deutsch, G. P.; Gray, R.; Kwong, D. L. W.; Pai, V. R.; Senanayake, F.; Boccardo, F.; Rubagotti, A.; Baum, M.; Forsyth, S.; Hackshaw, A.; Houghton, J.; Ledermann, J.; Monson, K.; Tobias, J. S.; Carlomagno, C.; De Laurentiis, M.; De Placido, S.; Williams, L.; Hayes, D.; Pierce, L. J.; Broglio, K.; Buzdar, A. U.; Love, R. R.; Ahlgren, J.; Garmo, H.; Holmberg, L.; Liljegren, G.; Lindman, H.; Wärnberg, F.; Asmar, L.; Jones, S. E.; Gluz, O.; Harbeck, N.; Liedtke, C.; Nitz, U.; Litton, A.; Wallgren, A.; Karlsson, P.; Linderholm, B. K.; Chlebowski, R. T.; Caffier, H.
Article Title: Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials
Abstract: Background: As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen. Methods: We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21 457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment. Findings: In oestrogen receptor (ER)-positive disease (n=10 645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0-4 and RR 0·68 [0·06] during years 5-9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10-14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10-19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0-4, 0·66 [0·05] during years 5-9, and 0·68 [0·08] during years 10-14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality. Interpretation: 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the only recorded factor importantly predictive of the proportional reductions. Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen. Funding: Cancer Research UK, British Heart Foundation, and Medical Research Council.
Keywords: cancer chemotherapy; cancer recurrence; drug efficacy; treatment duration; cancer adjuvant therapy; recurrence risk; breast cancer; cancer mortality; age; thromboembolism; lymph node; tamoxifen; estrogen receptor; progesterone receptor; risk reduction; uterus cancer; meta analysis; randomized controlled trial (topic); human; priority journal; article
Journal Title: Lancet
Volume: 378
Issue: 9793
ISSN: 0140-6736
Publisher: Elsevier Science, Inc.  
Date Published: 2011-08-27
Start Page: 771
End Page: 784
Language: English
DOI: 10.1016/s0140-6736(11)60993-8
PUBMED: 21802721
PROVIDER: scopus
PMCID: PMC3163848
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Clifford Hudis
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