Tamoxifen for early breast cancer: An overview of the randomised trials

O. Abe, R. Abe, K. Enomoto, K. Kikuchi, H. Koyama, Y. Nomura, K. Sakai, K. Sugimachi, T. Tominaga, J. Uchino, M. Yoshida, A. O. van de Velde, J. A. van Dongen, J. B. Vermorken, G. Giokas, B. Lissaios, V. J. Harvey, T. M. Holdaway, R. G. Kay, B. H. MasonA. Coates, J. F. Forbes, C. Focan, J. P. Lobelle, U. Peek, G. D. Oates, J. Powell, M. Durand, L. Mauriac, S. Bartholomeus, M. J. Piccart, R. S. Gelman, J. R. Harris, C. L. Shapiro, A. K. Hancock, M. B. Masood, D. Parker, J. J. Price, S. Jackson, J. Ragaz, T. Delozier, J. Macé-Lesec'h, J. L. Haybittle, C. Cirrincione, I. C. Henderson, A. Korzun, R. B. Weiss, W. C. Wood, M. Baum, J. Houghton, D. Riley, D. M. Dent, C. A. Gudgeon, A. Hacking, K. Horgan, L. Hughes, H. J. Stewart, N. H. Gordon, H. L. Davis, P. Romestaing, Y. Lehingue, J. R. Owen, P. Meier, A. Howell, G. G. Ribeiro, R. Swindell, J. Albano, C. F. de Oliveira, H. Gervásio, J. Gordilho, B. Carstensen, T. Palshof, H. Johansen, S. Korzeniowski, J. Skolyszewski, S. M. Portnoj, K. W. Andersen, C. K. Axelsson, M. Blichert-Toft, H. T. Mouridsen, M. Overgaard, C. Rose, N. Corcoran, H. J. Trampisch, R. L. Comis, N. E. Davidson, R. Gray, N. Robert, D. C. Tormey, W. Wood, J. Rossbach, L. Bijnens, C. van de Velde, M. P. Cunningham, G. Bastert, H. Rauschecker, R. Sauer, W. Sauerbrei, A. Schauer, M. Schumacher, A. de Schryver, M. Belfiglio, E. Mari, A. Nicolucci, N. Scorpiglione, H. M A Yosef, C. S. McArdle, D. C. Smith, P. C. Lara, F. Boccardo, A. Rubagotti, A. Erazo, J. Y. Medina, M. Izuo, Y. Morishita, A. Bentley, Z. Doran, I. S. Fentiman, J. L. Hayward, R. D. Rubens, M. Kaufmann, W. Jonat, D. von Fournier, M. Kaufmann, G. Fountzilas, P. Klefstrom, C. Blomqvist, J. Cuzick, R. Margreiter, M. Castiglione, F. Cavalli, J. Collins, J. Forbes, R. D. Gelber, A. Goldhirsch, J. Lindtner, K. N. Price, C. M. Rudenstam, H. J. Senn, J. M. Bliss, R. C. Coombes, M. Marty, R. Borovik, G. Brufman, H. Hayat, E. Robinson, N. Wigler, F. Pannuti, S. Takashima, T. Yasutomi, H. Sonoo, J. Yamashita, M. Ogawa, Y. Nomura, P. S G J Hupperets, J. Bonte, I. Tengrup, L. Tennvall-Nittby, P. Martin, S. Romain, D. Ahmann, D. J. Schaid, A. U. Buzdar, T. Smith, T. Hakes, L. Norton, R. Wittes, R. de la Huerta, M. G. Sainz, G. Bonadonna, M. del Vecchio, P. Valagussa, U. Veronesi, J. B. Dubois, A. R. Bianco, M. E. Lippman, L. J. Pierce, R. Simon, S. M. Steinberg, J. D. Myles, J. L. Pater, K. I. Pritchard, S. Anderson, 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, L. G. Larsson, J. P. Lythgoe, R. Swindell, M. Kissin, E. Hannisdal, J. E. Varhaug, R. Nissen-Meyer, R. W. Blamey, A. K. Mitchell, J. F R Robertson, Y. Nakamura, G. Mathé, J. L. Misset, H. T. Abu-Zahra, E. A. Clarke, J. R. McLaughlin, R. M. Clark, M. Levine, K. Morimoto, K. Sawa, Y. Takatsuka, S. Gundersen, M. Hauer-Jensen, H. Host, E. Crossley, A. Harris, C. Baker, A. Beighton, M. Clarke, R. Collins, C. Davies, T. Elphinstone, V. Evans, J. Godwin, R. Gray, E. Greaves, C. Harwood, A. Headon, C. Hicks, D. Jackson, S. James, E. Lau, P. McGale, G. Mead, H. Monaghan, S. Mozley, A. Naughten, R. Peto, A. Tooth, K. Wheatley, P. Rambert, B. Asselain, R. J. Salmon, J. R. Vilcoq, R. Arriagada, C. Hill, A. Laplanche, M. G. Lê, M. Spielmann, G. Cocconi, B. di Blasio, R. Catalano, R. H. Creech, J. Brockschmidt, M. R. Cooper, O. Andrysek, J. Barkmanova, C. I. Falkson, M. Abraham, J. G M Klijn, A. D. Treurniet-Donker, W. L J van Putten, D. Easton, T. J. Powles, J. C. Gazet, V. Semiglazov, A. Businico, S. Sardinia, N. Deshpande, L. di Martino, P. Douglas, A. Hacking, H. Host, A. Lindtner, G. Notter, A. J S Bryant, G. H. Ewing, J. L. Krushen-Kosloski, R. Nissen-Meyer, A. P M Forrest, W. Jack, C. McDonald, H. J. Stewart, T. R. Möller, S. Rydén, J. Carstensen, T. Hatschek, M. Söderberg, J. T. Carpenter, K. Albain, J. Crowley, S. Green, S. Martino, C. K. Osborne, P. M. Ravdin, L. E. Rutqvist, A. Wallgren, L. E. Holm, M. Castiglione, A. Goldhirsch, 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, A. Naja, J. Bahi, M. Reid, M. Spittle, F. Senanayake, R. R. Love, D. L. de Mets, J. Bergh, L. Holmberg, P. Sevelda, C. C. Zielinsky, M. Gnant, R. Jakesz, R. B. Buchanan, G. T. Royle, J. A. Dunn, W. M. Gillespie, K. Kelly, J. M. Morrison, A. Litton, R. T. Chlebowski, W. R. Bezwoda, H. Caffier

Research output: Contribution to journalArticle

Abstract

Background: There have been many randomised trials of adjuvant tamoxifen among women with early breast cancer, and an updated overview of their results is presented. Methods: In 1995, information was sought on each woman in any randomised trial that began before 1990 of adjuvant tamoxifen versus no tamoxifen before recurrence. Information was obtained and analysed centrally on each of 37,000 women in 55 such trials, comprising about 87% of the worldwide evidence. Compared with the previous such overview, this approximately doubles the amount of evidence from trials of about 5 years of tamoxifen and, taking all trials together, on events occurring more than 5 years after randomisation. Findings: Nearly 8000 of the women had a low, or zero, level of the oestrogen-receptor protein (ER) measured in their primary tumour. Among them, the overall effects of tamoxifen appeared to be small, and subsequent analyses of recurrence and total mortality are restricted to the remaining women (18,000 with ER-positive tumours, plus nearly 12,000 more with untested tumours, of which an estimated 8000 would have been ER-positive). For trials of 1 year, 2 years, and about 5 years of adjuvant tamoxifen, the proportional recurrence reductions produced among these 30,000 women during about 10 years of follow-up were 21% (SD 3), 29% (SD 2), and 47% (SD 3), respectively, with a highly significant trend towards greater effect with longer treatment (χ1 2 = 52.0, 2p <0.00001). The corresponding proportional mortality reductions were 12% (SD 3), 17% (SD 3), and 26% (SD 4), respectively, and again the test for trend was significant (χ1 2 = 8.8) 2p = 0.003). The absolute improvement in recurrence was greater during the first 5 years, whereas the improvement in survival grew steadily larger throughout the first 10 years. The proportional mortality reductions were similar for women with node-positive and node-negative disease, but the absolute mortality reductions were greater in node-positive women. In the trials of about 5 years of adjuvant tamoxifen the absolute improvements in 10-year survival were 10.9% (SD 2.5) for node-positive (61.4% vs 50.5% survival, 2p <0.00001) and 5.6% (SD 1.3) for node-negative (78.9% vs 73.3% survival, 2p <0.00001). These benefits appeared to be largely irrespective of age, menopausal status, daily tamoxifen dose (which was generally 20 mg), and of whether chemotherapy had been given to both groups. In terms of other outcomes among all women studied (ie, including those with 'ER-poor' tumours), the proportional reductions in contralateral breast cancer were 13% (SD 13), 26% (SD 9), and 47% (SD 9) in the trials of 1, 2, or about 5 years of adjuvant tamoxifen. The incidence of endometrial cancer was approximately doubled in trials of 1 or 2 years of tamoxifen and approximately quadrupled in trials of 5 years of tamoxifen (although the number of cases was small and these ratios were not significantly different from each other). The absolute decrease in contralateral breast cancer was about twice as large as the absolute increase in the incidence of endometrial cancer. Tamoxifen had no apparent effect on the incidence of colorectal cancer or, after exclusion of deaths from breast or endometrial cancer, on any of the other main categories of cause of death (total nearly 2000 such deaths; overall relative risk 0.99 [SD 0.05]). Interpretation: For women with tumours that have been reliably shown to be ER-negative, adjuvant tamoxifen remains a matter for research. However, some years of adjuvant tamoxifen treatment substantially improves the 10-year survival of women with ER-positive tumours and of women whose tumours are of unknown ER status, with the proportional reductions in breast cancer recurrence and in mortality appearing to be largely unaffected by other patient characteristics or treatments.

Original languageEnglish
Pages (from-to)1451-1467
Number of pages17
JournalLancet
Volume351
Issue number9114
DOIs
Publication statusPublished - May 16 1998

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Tamoxifen
Breast Neoplasms
Recurrence
Endometrial Neoplasms
Survival
Neoplasms
Mortality
Incidence
Random Allocation
Cause of Death
Colorectal Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Nomura, Y., ... Caffier, H. (1998). Tamoxifen for early breast cancer: An overview of the randomised trials. Lancet, 351(9114), 1451-1467. https://doi.org/10.1016/S0140-6736(97)11423-4

Tamoxifen for early breast cancer : An overview of the randomised trials. / Abe, O.; Abe, R.; Enomoto, K.; Kikuchi, K.; Koyama, H.; Nomura, Y.; Sakai, K.; Sugimachi, K.; Tominaga, T.; Uchino, J.; Yoshida, M.; van de Velde, A. O.; van Dongen, J. A.; Vermorken, J. B.; Giokas, G.; Lissaios, B.; Harvey, V. J.; Holdaway, T. M.; Kay, R. G.; Mason, B. H.; Coates, A.; Forbes, J. F.; Focan, C.; Lobelle, J. P.; Peek, U.; Oates, G. D.; Powell, J.; Durand, M.; Mauriac, L.; Bartholomeus, S.; Piccart, M. J.; Gelman, R. S.; Harris, J. R.; Shapiro, C. L.; Hancock, A. K.; Masood, M. B.; Parker, D.; Price, J. J.; Jackson, S.; Ragaz, J.; Delozier, T.; Macé-Lesec'h, J.; Haybittle, J. L.; Cirrincione, C.; Henderson, I. C.; Korzun, A.; Weiss, R. B.; Wood, W. C.; Baum, M.; Houghton, J.; Riley, D.; Dent, D. M.; Gudgeon, C. A.; Hacking, A.; Horgan, K.; Hughes, L.; Stewart, H. J.; Gordon, N. H.; Davis, H. L.; Romestaing, P.; Lehingue, Y.; Owen, J. R.; Meier, P.; Howell, A.; Ribeiro, G. G.; Swindell, R.; Albano, J.; de Oliveira, C. F.; Gervásio, H.; Gordilho, J.; Carstensen, B.; Palshof, T.; Johansen, H.; Korzeniowski, S.; Skolyszewski, J.; Portnoj, S. M.; Andersen, K. W.; Axelsson, C. K.; Blichert-Toft, M.; Mouridsen, H. T.; Overgaard, M.; Rose, C.; Corcoran, N.; Trampisch, H. J.; Comis, R. L.; Davidson, N. E.; Gray, R.; Robert, N.; Tormey, D. C.; Wood, W.; Rossbach, J.; Bijnens, L.; van de Velde, C.; Cunningham, M. P.; Bastert, G.; Rauschecker, H.; Sauer, R.; Sauerbrei, W.; Schauer, A.; Schumacher, M.; de Schryver, A.; Belfiglio, M.; Mari, E.; Nicolucci, A.; Scorpiglione, N.; Yosef, H. M A; McArdle, C. S.; Smith, D. C.; Lara, P. C.; Boccardo, F.; Rubagotti, A.; Erazo, A.; Medina, J. Y.; Izuo, M.; Morishita, Y.; Bentley, A.; Doran, Z.; Fentiman, I. S.; Hayward, J. L.; Rubens, R. D.; Kaufmann, M.; Jonat, W.; von Fournier, D.; Kaufmann, M.; Fountzilas, G.; Klefstrom, P.; Blomqvist, C.; Cuzick, J.; Margreiter, R.; Castiglione, M.; Cavalli, F.; Collins, J.; Forbes, J.; Gelber, R. D.; Goldhirsch, A.; Lindtner, J.; Price, K. N.; Rudenstam, C. M.; Senn, H. J.; Bliss, J. M.; Coombes, R. C.; Marty, M.; Borovik, R.; Brufman, G.; Hayat, H.; Robinson, E.; Wigler, N.; Pannuti, F.; Takashima, S.; Yasutomi, T.; Sonoo, H.; Yamashita, J.; Ogawa, M.; Nomura, Y.; Hupperets, P. S G J; Bonte, J.; Tengrup, I.; Tennvall-Nittby, L.; Martin, P.; Romain, S.; Ahmann, D.; Schaid, D. J.; Buzdar, A. U.; Smith, T.; Hakes, T.; Norton, L.; Wittes, R.; de la Huerta, R.; Sainz, M. G.; Bonadonna, G.; del Vecchio, M.; Valagussa, P.; Veronesi, U.; Dubois, J. B.; Bianco, A. R.; Lippman, M. E.; Pierce, L. J.; Simon, R.; Steinberg, S. M.; Myles, J. D.; Pater, J. L.; Pritchard, K. I.; Anderson, S.; 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.; Larsson, L. G.; Lythgoe, J. P.; Swindell, R.; Kissin, M.; Hannisdal, E.; Varhaug, J. E.; Nissen-Meyer, R.; Blamey, R. W.; Mitchell, A. K.; Robertson, J. F R; Nakamura, Y.; Mathé, G.; Misset, J. L.; Abu-Zahra, H. T.; Clarke, E. A.; McLaughlin, J. R.; Clark, R. M.; Levine, M.; Morimoto, K.; Sawa, K.; Takatsuka, Y.; Gundersen, S.; Hauer-Jensen, M.; Host, H.; Crossley, E.; Harris, A.; Baker, C.; Beighton, A.; Clarke, M.; Collins, R.; Davies, C.; Elphinstone, T.; Evans, V.; Godwin, J.; Gray, R.; Greaves, E.; Harwood, C.; Headon, A.; Hicks, C.; Jackson, D.; James, S.; Lau, E.; McGale, P.; Mead, G.; Monaghan, H.; Mozley, S.; Naughten, A.; Peto, R.; Tooth, A.; Wheatley, K.; Rambert, P.; Asselain, B.; Salmon, R. J.; Vilcoq, J. R.; Arriagada, R.; Hill, C.; Laplanche, A.; Lê, M. G.; Spielmann, M.; Cocconi, G.; di Blasio, B.; Catalano, R.; Creech, R. H.; Brockschmidt, J.; Cooper, M. R.; Andrysek, O.; Barkmanova, J.; Falkson, C. I.; Abraham, M.; Klijn, J. G M; Treurniet-Donker, A. D.; van Putten, W. L J; Easton, D.; Powles, T. J.; Gazet, J. C.; Semiglazov, V.; Businico, A.; Sardinia, S.; Deshpande, N.; di Martino, L.; Douglas, P.; Hacking, A.; Host, H.; Lindtner, A.; Notter, G.; Bryant, A. J S; Ewing, G. H.; Krushen-Kosloski, J. L.; Nissen-Meyer, R.; Forrest, A. P M; Jack, W.; McDonald, C.; Stewart, H. J.; Möller, T. R.; Rydén, S.; Carstensen, J.; Hatschek, T.; Söderberg, M.; Carpenter, J. T.; Albain, K.; Crowley, J.; Green, S.; Martino, S.; Osborne, C. K.; Ravdin, P. M.; Rutqvist, L. E.; Wallgren, A.; Holm, L. E.; Castiglione, M.; Goldhirsch, A.; 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.; Naja, A.; Bahi, J.; Reid, M.; Spittle, M.; Senanayake, F.; Love, R. R.; de Mets, D. L.; Bergh, J.; Holmberg, L.; Sevelda, P.; Zielinsky, C. C.; Gnant, M.; Jakesz, R.; Buchanan, R. B.; Royle, G. T.; Dunn, J. A.; Gillespie, W. M.; Kelly, K.; Morrison, J. M.; Litton, A.; Chlebowski, R. T.; Bezwoda, W. R.; Caffier, H.

In: Lancet, Vol. 351, No. 9114, 16.05.1998, p. 1451-1467.

Research output: Contribution to journalArticle

Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Nomura, Y, Sakai, K, Sugimachi, K, Tominaga, T, Uchino, J, Yoshida, M, van de Velde, AO, van Dongen, JA, Vermorken, JB, Giokas, G, Lissaios, B, Harvey, VJ, Holdaway, TM, Kay, RG, Mason, BH, Coates, A, Forbes, JF, Focan, C, Lobelle, JP, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Bartholomeus, S, Piccart, MJ, Gelman, RS, Harris, JR, Shapiro, CL, Hancock, AK, Masood, MB, Parker, D, Price, JJ, Jackson, S, Ragaz, J, Delozier, T, Macé-Lesec'h, J, Haybittle, JL, Cirrincione, C, Henderson, IC, Korzun, A, Weiss, RB, Wood, WC, Baum, M, Houghton, J, Riley, D, Dent, DM, Gudgeon, CA, Hacking, A, Horgan, K, Hughes, L, Stewart, HJ, Gordon, NH, Davis, HL, Romestaing, P, Lehingue, Y, Owen, JR, Meier, P, Howell, A, Ribeiro, GG, Swindell, R, Albano, J, de Oliveira, CF, Gervásio, H, Gordilho, J, Carstensen, B, Palshof, T, Johansen, H, Korzeniowski, S, Skolyszewski, J, Portnoj, SM, Andersen, KW, Axelsson, CK, Blichert-Toft, M, Mouridsen, HT, Overgaard, M, Rose, C, Corcoran, N, Trampisch, HJ, Comis, RL, Davidson, NE, Gray, R, Robert, N, Tormey, DC, Wood, W, Rossbach, J, Bijnens, L, van de Velde, C, Cunningham, MP, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Schumacher, M, de Schryver, A, Belfiglio, M, Mari, E, Nicolucci, A, Scorpiglione, N, Yosef, HMA, McArdle, CS, Smith, DC, Lara, PC, Boccardo, F, Rubagotti, A, Erazo, A, Medina, JY, Izuo, M, Morishita, Y, Bentley, A, Doran, Z, Fentiman, IS, Hayward, JL, Rubens, RD, Kaufmann, M, Jonat, W, von Fournier, D, Kaufmann, M, Fountzilas, G, Klefstrom, P, Blomqvist, C, Cuzick, J, Margreiter, R, Castiglione, M, Cavalli, F, Collins, J, Forbes, J, Gelber, RD, Goldhirsch, A, Lindtner, J, Price, KN, Rudenstam, CM, Senn, HJ, Bliss, JM, Coombes, RC, Marty, M, Borovik, R, Brufman, G, Hayat, H, Robinson, E, Wigler, N, Pannuti, F, Takashima, S, Yasutomi, T, Sonoo, H, Yamashita, J, Ogawa, M, Nomura, Y, Hupperets, PSGJ, Bonte, J, Tengrup, I, Tennvall-Nittby, L, Martin, P, Romain, S, Ahmann, D, Schaid, DJ, Buzdar, AU, Smith, T, Hakes, T, Norton, L, Wittes, R, de la Huerta, R, Sainz, MG, Bonadonna, G, del Vecchio, M, Valagussa, P, Veronesi, U, Dubois, JB, Bianco, AR, Lippman, ME, Pierce, LJ, Simon, R, Steinberg, SM, Myles, JD, Pater, JL, Pritchard, KI, Anderson, S, 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, Larsson, LG, Lythgoe, JP, Swindell, R, Kissin, M, Hannisdal, E, Varhaug, JE, Nissen-Meyer, R, Blamey, RW, Mitchell, AK, Robertson, JFR, Nakamura, Y, Mathé, G, Misset, JL, Abu-Zahra, HT, Clarke, EA, McLaughlin, JR, Clark, RM, Levine, M, Morimoto, K, Sawa, K, Takatsuka, Y, Gundersen, S, Hauer-Jensen, M, Host, H, Crossley, E, Harris, A, Baker, C, Beighton, A, Clarke, M, Collins, R, Davies, C, Elphinstone, T, Evans, V, Godwin, J, Gray, R, Greaves, E, Harwood, C, Headon, A, Hicks, C, Jackson, D, James, S, Lau, E, McGale, P, Mead, G, Monaghan, H, Mozley, S, Naughten, A, Peto, R, Tooth, A, Wheatley, K, Rambert, P, Asselain, B, Salmon, RJ, Vilcoq, JR, Arriagada, R, Hill, C, Laplanche, A, Lê, MG, Spielmann, M, Cocconi, G, di Blasio, B, Catalano, R, Creech, RH, Brockschmidt, J, Cooper, MR, Andrysek, O, Barkmanova, J, Falkson, CI, Abraham, M, Klijn, JGM, Treurniet-Donker, AD, van Putten, WLJ, Easton, D, Powles, TJ, Gazet, JC, Semiglazov, V, Businico, A, Sardinia, S, Deshpande, N, di Martino, L, Douglas, P, Hacking, A, Host, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Krushen-Kosloski, JL, Nissen-Meyer, R, Forrest, APM, Jack, W, McDonald, C, Stewart, HJ, Möller, TR, Rydén, S, Carstensen, J, Hatschek, T, Söderberg, M, Carpenter, JT, Albain, K, Crowley, J, Green, S, Martino, S, Osborne, CK, Ravdin, PM, Rutqvist, LE, Wallgren, A, Holm, LE, Castiglione, M, Goldhirsch, A, Senn, HJ, Thürlimann, B, Brenner, H, Hercbergs, A, Yoshimoto, M, DeBoer, G, Paterson, AHG, Pritchard, KI, Meakin, JW, Panzarella, T, Pritchard, KI, Naja, A, Bahi, J, Reid, M, Spittle, M, Senanayake, F, Love, RR, de Mets, DL, Bergh, J, Holmberg, L, Sevelda, P, Zielinsky, CC, Gnant, M, Jakesz, R, Buchanan, RB, Royle, GT, Dunn, JA, Gillespie, WM, Kelly, K, Morrison, JM, Litton, A, Chlebowski, RT, Bezwoda, WR & Caffier, H 1998, 'Tamoxifen for early breast cancer: An overview of the randomised trials', Lancet, vol. 351, no. 9114, pp. 1451-1467. https://doi.org/10.1016/S0140-6736(97)11423-4
Abe O, Abe R, Enomoto K, Kikuchi K, Koyama H, Nomura Y et al. Tamoxifen for early breast cancer: An overview of the randomised trials. Lancet. 1998 May 16;351(9114):1451-1467. https://doi.org/10.1016/S0140-6736(97)11423-4
Abe, O. ; Abe, R. ; Enomoto, K. ; Kikuchi, K. ; Koyama, H. ; Nomura, Y. ; Sakai, K. ; Sugimachi, K. ; Tominaga, T. ; Uchino, J. ; Yoshida, M. ; van de Velde, A. O. ; van Dongen, J. A. ; Vermorken, J. B. ; Giokas, G. ; Lissaios, B. ; Harvey, V. J. ; Holdaway, T. M. ; Kay, R. G. ; Mason, B. H. ; Coates, A. ; Forbes, J. F. ; Focan, C. ; Lobelle, J. P. ; Peek, U. ; Oates, G. D. ; Powell, J. ; Durand, M. ; Mauriac, L. ; Bartholomeus, S. ; Piccart, M. J. ; Gelman, R. S. ; Harris, J. R. ; Shapiro, C. L. ; Hancock, A. K. ; Masood, M. B. ; Parker, D. ; Price, J. J. ; Jackson, S. ; Ragaz, J. ; Delozier, T. ; Macé-Lesec'h, J. ; Haybittle, J. L. ; Cirrincione, C. ; Henderson, I. C. ; Korzun, A. ; Weiss, R. B. ; Wood, W. C. ; Baum, M. ; Houghton, J. ; Riley, D. ; Dent, D. M. ; Gudgeon, C. A. ; Hacking, A. ; Horgan, K. ; Hughes, L. ; Stewart, H. J. ; Gordon, N. H. ; Davis, H. L. ; Romestaing, P. ; Lehingue, Y. ; Owen, J. R. ; Meier, P. ; Howell, A. ; Ribeiro, G. G. ; Swindell, R. ; Albano, J. ; de Oliveira, C. F. ; Gervásio, H. ; Gordilho, J. ; Carstensen, B. ; Palshof, T. ; Johansen, H. ; Korzeniowski, S. ; Skolyszewski, J. ; Portnoj, S. M. ; Andersen, K. W. ; Axelsson, C. K. ; Blichert-Toft, M. ; Mouridsen, H. T. ; Overgaard, M. ; Rose, C. ; Corcoran, N. ; Trampisch, H. J. ; Comis, R. L. ; Davidson, N. E. ; Gray, R. ; Robert, N. ; Tormey, D. C. ; Wood, W. ; Rossbach, J. ; Bijnens, L. ; van de Velde, C. ; Cunningham, M. P. ; Bastert, G. ; Rauschecker, H. ; Sauer, R. ; Sauerbrei, W. ; Schauer, A. ; Schumacher, M. ; de Schryver, A. ; Belfiglio, M. ; Mari, E. ; Nicolucci, A. ; Scorpiglione, N. ; Yosef, H. M A ; McArdle, C. S. ; Smith, D. C. ; Lara, P. C. ; Boccardo, F. ; Rubagotti, A. ; Erazo, A. ; Medina, J. Y. ; Izuo, M. ; Morishita, Y. ; Bentley, A. ; Doran, Z. ; Fentiman, I. S. ; Hayward, J. L. ; Rubens, R. D. ; Kaufmann, M. ; Jonat, W. ; von Fournier, D. ; Kaufmann, M. ; Fountzilas, G. ; Klefstrom, P. ; Blomqvist, C. ; Cuzick, J. ; Margreiter, R. ; Castiglione, M. ; Cavalli, F. ; Collins, J. ; Forbes, J. ; Gelber, R. D. ; Goldhirsch, A. ; Lindtner, J. ; Price, K. N. ; Rudenstam, C. M. ; Senn, H. J. ; Bliss, J. M. ; Coombes, R. C. ; Marty, M. ; Borovik, R. ; Brufman, G. ; Hayat, H. ; Robinson, E. ; Wigler, N. ; Pannuti, F. ; Takashima, S. ; Yasutomi, T. ; Sonoo, H. ; Yamashita, J. ; Ogawa, M. ; Nomura, Y. ; Hupperets, P. S G J ; Bonte, J. ; Tengrup, I. ; Tennvall-Nittby, L. ; Martin, P. ; Romain, S. ; Ahmann, D. ; Schaid, D. J. ; Buzdar, A. U. ; Smith, T. ; Hakes, T. ; Norton, L. ; Wittes, R. ; de la Huerta, R. ; Sainz, M. G. ; Bonadonna, G. ; del Vecchio, M. ; Valagussa, P. ; Veronesi, U. ; Dubois, J. B. ; Bianco, A. R. ; Lippman, M. E. ; Pierce, L. J. ; Simon, R. ; Steinberg, S. M. ; Myles, J. D. ; Pater, J. L. ; Pritchard, K. I. ; Anderson, S. ; 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. ; Larsson, L. G. ; Lythgoe, J. P. ; Swindell, R. ; Kissin, M. ; Hannisdal, E. ; Varhaug, J. E. ; Nissen-Meyer, R. ; Blamey, R. W. ; Mitchell, A. K. ; Robertson, J. F R ; Nakamura, Y. ; Mathé, G. ; Misset, J. L. ; Abu-Zahra, H. T. ; Clarke, E. A. ; McLaughlin, J. R. ; Clark, R. M. ; Levine, M. ; Morimoto, K. ; Sawa, K. ; Takatsuka, Y. ; Gundersen, S. ; Hauer-Jensen, M. ; Host, H. ; Crossley, E. ; Harris, A. ; Baker, C. ; Beighton, A. ; Clarke, M. ; Collins, R. ; Davies, C. ; Elphinstone, T. ; Evans, V. ; Godwin, J. ; Gray, R. ; Greaves, E. ; Harwood, C. ; Headon, A. ; Hicks, C. ; Jackson, D. ; James, S. ; Lau, E. ; McGale, P. ; Mead, G. ; Monaghan, H. ; Mozley, S. ; Naughten, A. ; Peto, R. ; Tooth, A. ; Wheatley, K. ; Rambert, P. ; Asselain, B. ; Salmon, R. J. ; Vilcoq, J. R. ; Arriagada, R. ; Hill, C. ; Laplanche, A. ; Lê, M. G. ; Spielmann, M. ; Cocconi, G. ; di Blasio, B. ; Catalano, R. ; Creech, R. H. ; Brockschmidt, J. ; Cooper, M. R. ; Andrysek, O. ; Barkmanova, J. ; Falkson, C. I. ; Abraham, M. ; Klijn, J. G M ; Treurniet-Donker, A. D. ; van Putten, W. L J ; Easton, D. ; Powles, T. J. ; Gazet, J. C. ; Semiglazov, V. ; Businico, A. ; Sardinia, S. ; Deshpande, N. ; di Martino, L. ; Douglas, P. ; Hacking, A. ; Host, H. ; Lindtner, A. ; Notter, G. ; Bryant, A. J S ; Ewing, G. H. ; Krushen-Kosloski, J. L. ; Nissen-Meyer, R. ; Forrest, A. P M ; Jack, W. ; McDonald, C. ; Stewart, H. J. ; Möller, T. R. ; Rydén, S. ; Carstensen, J. ; Hatschek, T. ; Söderberg, M. ; Carpenter, J. T. ; Albain, K. ; Crowley, J. ; Green, S. ; Martino, S. ; Osborne, C. K. ; Ravdin, P. M. ; Rutqvist, L. E. ; Wallgren, A. ; Holm, L. E. ; Castiglione, M. ; Goldhirsch, A. ; 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. ; Naja, A. ; Bahi, J. ; Reid, M. ; Spittle, M. ; Senanayake, F. ; Love, R. R. ; de Mets, D. L. ; Bergh, J. ; Holmberg, L. ; Sevelda, P. ; Zielinsky, C. C. ; Gnant, M. ; Jakesz, R. ; Buchanan, R. B. ; Royle, G. T. ; Dunn, J. A. ; Gillespie, W. M. ; Kelly, K. ; Morrison, J. M. ; Litton, A. ; Chlebowski, R. T. ; Bezwoda, W. R. ; Caffier, H. / Tamoxifen for early breast cancer : An overview of the randomised trials. In: Lancet. 1998 ; Vol. 351, No. 9114. pp. 1451-1467.
@article{cb34653b06b94bc7bc93c8b49ffc0a3a,
title = "Tamoxifen for early breast cancer: An overview of the randomised trials",
abstract = "Background: There have been many randomised trials of adjuvant tamoxifen among women with early breast cancer, and an updated overview of their results is presented. Methods: In 1995, information was sought on each woman in any randomised trial that began before 1990 of adjuvant tamoxifen versus no tamoxifen before recurrence. Information was obtained and analysed centrally on each of 37,000 women in 55 such trials, comprising about 87{\%} of the worldwide evidence. Compared with the previous such overview, this approximately doubles the amount of evidence from trials of about 5 years of tamoxifen and, taking all trials together, on events occurring more than 5 years after randomisation. Findings: Nearly 8000 of the women had a low, or zero, level of the oestrogen-receptor protein (ER) measured in their primary tumour. Among them, the overall effects of tamoxifen appeared to be small, and subsequent analyses of recurrence and total mortality are restricted to the remaining women (18,000 with ER-positive tumours, plus nearly 12,000 more with untested tumours, of which an estimated 8000 would have been ER-positive). For trials of 1 year, 2 years, and about 5 years of adjuvant tamoxifen, the proportional recurrence reductions produced among these 30,000 women during about 10 years of follow-up were 21{\%} (SD 3), 29{\%} (SD 2), and 47{\%} (SD 3), respectively, with a highly significant trend towards greater effect with longer treatment (χ1 2 = 52.0, 2p <0.00001). The corresponding proportional mortality reductions were 12{\%} (SD 3), 17{\%} (SD 3), and 26{\%} (SD 4), respectively, and again the test for trend was significant (χ1 2 = 8.8) 2p = 0.003). The absolute improvement in recurrence was greater during the first 5 years, whereas the improvement in survival grew steadily larger throughout the first 10 years. The proportional mortality reductions were similar for women with node-positive and node-negative disease, but the absolute mortality reductions were greater in node-positive women. In the trials of about 5 years of adjuvant tamoxifen the absolute improvements in 10-year survival were 10.9{\%} (SD 2.5) for node-positive (61.4{\%} vs 50.5{\%} survival, 2p <0.00001) and 5.6{\%} (SD 1.3) for node-negative (78.9{\%} vs 73.3{\%} survival, 2p <0.00001). These benefits appeared to be largely irrespective of age, menopausal status, daily tamoxifen dose (which was generally 20 mg), and of whether chemotherapy had been given to both groups. In terms of other outcomes among all women studied (ie, including those with 'ER-poor' tumours), the proportional reductions in contralateral breast cancer were 13{\%} (SD 13), 26{\%} (SD 9), and 47{\%} (SD 9) in the trials of 1, 2, or about 5 years of adjuvant tamoxifen. The incidence of endometrial cancer was approximately doubled in trials of 1 or 2 years of tamoxifen and approximately quadrupled in trials of 5 years of tamoxifen (although the number of cases was small and these ratios were not significantly different from each other). The absolute decrease in contralateral breast cancer was about twice as large as the absolute increase in the incidence of endometrial cancer. Tamoxifen had no apparent effect on the incidence of colorectal cancer or, after exclusion of deaths from breast or endometrial cancer, on any of the other main categories of cause of death (total nearly 2000 such deaths; overall relative risk 0.99 [SD 0.05]). Interpretation: For women with tumours that have been reliably shown to be ER-negative, adjuvant tamoxifen remains a matter for research. However, some years of adjuvant tamoxifen treatment substantially improves the 10-year survival of women with ER-positive tumours and of women whose tumours are of unknown ER status, with the proportional reductions in breast cancer recurrence and in mortality appearing to be largely unaffected by other patient characteristics or treatments.",
author = "O. Abe and R. Abe and K. Enomoto and K. Kikuchi and H. Koyama and Y. Nomura and K. Sakai and K. Sugimachi and T. Tominaga and J. Uchino and M. Yoshida and {van de Velde}, {A. O.} and {van Dongen}, {J. A.} and Vermorken, {J. B.} and G. Giokas and B. Lissaios and Harvey, {V. J.} and Holdaway, {T. M.} and Kay, {R. G.} and Mason, {B. H.} and A. Coates and Forbes, {J. F.} and C. Focan and Lobelle, {J. P.} and U. Peek and Oates, {G. D.} and J. Powell and M. Durand and L. Mauriac and S. Bartholomeus and Piccart, {M. J.} and Gelman, {R. S.} and Harris, {J. R.} and Shapiro, {C. L.} and Hancock, {A. K.} and Masood, {M. B.} and D. Parker and Price, {J. J.} and S. Jackson and J. Ragaz and T. Delozier and J. Mac{\'e}-Lesec'h and Haybittle, {J. L.} and C. Cirrincione and Henderson, {I. C.} and A. Korzun and Weiss, {R. B.} and Wood, {W. C.} and M. Baum and J. Houghton and D. Riley and Dent, {D. M.} and Gudgeon, {C. A.} and A. Hacking and K. Horgan and L. Hughes and Stewart, {H. J.} and Gordon, {N. H.} and Davis, {H. L.} and P. Romestaing and Y. Lehingue and Owen, {J. R.} and P. Meier and A. Howell and Ribeiro, {G. G.} and R. Swindell and J. Albano and {de Oliveira}, {C. F.} and H. Gerv{\'a}sio and J. Gordilho and B. Carstensen and T. Palshof and H. Johansen and S. Korzeniowski and J. Skolyszewski and Portnoj, {S. M.} and Andersen, {K. W.} and Axelsson, {C. K.} and M. Blichert-Toft and Mouridsen, {H. T.} and M. Overgaard and C. Rose and N. Corcoran and Trampisch, {H. J.} and Comis, {R. L.} and Davidson, {N. E.} and R. Gray and N. Robert and Tormey, {D. C.} and W. Wood and J. Rossbach and L. Bijnens and {van de Velde}, C. and Cunningham, {M. P.} and G. Bastert and H. Rauschecker and R. Sauer and W. Sauerbrei and A. Schauer and M. Schumacher and {de Schryver}, A. and M. Belfiglio and E. Mari and A. Nicolucci and N. Scorpiglione and Yosef, {H. M A} and McArdle, {C. S.} and Smith, {D. C.} and Lara, {P. C.} and F. Boccardo and A. Rubagotti and A. Erazo and Medina, {J. Y.} and M. Izuo and Y. Morishita and A. Bentley and Z. Doran and Fentiman, {I. S.} and Hayward, {J. L.} and Rubens, {R. D.} and M. Kaufmann and W. Jonat and {von Fournier}, D. and M. Kaufmann and G. Fountzilas and P. Klefstrom and C. Blomqvist and J. Cuzick and R. Margreiter and M. Castiglione and F. Cavalli 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 Coombes, {R. C.} and M. Marty and R. Borovik and G. Brufman and H. Hayat and E. Robinson and N. Wigler and F. Pannuti and S. Takashima and T. Yasutomi and H. Sonoo and J. Yamashita and M. Ogawa and Y. Nomura and Hupperets, {P. S G J} and J. Bonte and I. Tengrup and L. Tennvall-Nittby and P. Martin and S. Romain and D. Ahmann and Schaid, {D. J.} and Buzdar, {A. U.} and T. Smith and T. Hakes and L. Norton and R. Wittes and {de la Huerta}, R. and Sainz, {M. G.} and G. Bonadonna and {del Vecchio}, M. and P. Valagussa and U. Veronesi and Dubois, {J. B.} and Bianco, {A. R.} and Lippman, {M. E.} and Pierce, {L. J.} and R. Simon and Steinberg, {S. M.} and Myles, {J. D.} and Pater, {J. L.} and Pritchard, {K. I.} and S. Anderson 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 Larsson, {L. G.} and Lythgoe, {J. P.} and R. Swindell and M. Kissin and E. Hannisdal and Varhaug, {J. E.} and R. Nissen-Meyer and Blamey, {R. W.} and Mitchell, {A. K.} and Robertson, {J. F R} and Y. Nakamura and G. Math{\'e} and Misset, {J. L.} and Abu-Zahra, {H. T.} and Clarke, {E. A.} and McLaughlin, {J. R.} and Clark, {R. M.} and M. Levine and K. Morimoto and K. Sawa and Y. Takatsuka and S. Gundersen and M. Hauer-Jensen and H. Host and E. Crossley and A. Harris and C. Baker and A. Beighton and M. Clarke and R. Collins and C. Davies and T. Elphinstone and V. Evans and J. Godwin and R. Gray and E. Greaves and C. Harwood and A. Headon and C. Hicks and D. Jackson and S. James and E. Lau and P. McGale and G. Mead and H. Monaghan and S. Mozley and A. Naughten and R. Peto and A. Tooth and K. Wheatley and P. Rambert 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 G. Cocconi and {di Blasio}, B. and R. Catalano and Creech, {R. H.} and J. Brockschmidt and Cooper, {M. R.} and O. Andrysek and J. Barkmanova and Falkson, {C. I.} and M. Abraham and Klijn, {J. G M} and Treurniet-Donker, {A. D.} and {van Putten}, {W. L J} and D. Easton and Powles, {T. J.} and Gazet, {J. C.} and V. Semiglazov and A. Businico and S. Sardinia and N. Deshpande and {di Martino}, L. and P. Douglas and A. Hacking and H. Host and A. Lindtner and G. Notter and Bryant, {A. J S} and Ewing, {G. H.} and Krushen-Kosloski, {J. L.} and R. Nissen-Meyer and Forrest, {A. P M} and W. Jack and C. McDonald and Stewart, {H. J.} and M{\"o}ller, {T. R.} and S. Ryd{\'e}n and J. Carstensen and T. Hatschek 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 Rutqvist, {L. E.} and A. Wallgren and Holm, {L. E.} and M. Castiglione and A. Goldhirsch 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 A. Naja and J. Bahi and M. Reid and M. Spittle and F. Senanayake and Love, {R. R.} and {de Mets}, {D. L.} and J. Bergh and L. Holmberg and P. Sevelda and Zielinsky, {C. C.} and M. Gnant and R. Jakesz and Buchanan, {R. B.} and Royle, {G. T.} and Dunn, {J. A.} and Gillespie, {W. M.} and K. Kelly and Morrison, {J. M.} and A. Litton and Chlebowski, {R. T.} and Bezwoda, {W. R.} and H. Caffier",
year = "1998",
month = "5",
day = "16",
doi = "10.1016/S0140-6736(97)11423-4",
language = "English",
volume = "351",
pages = "1451--1467",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Lancet Publishing Group",
number = "9114",

}

TY - JOUR

T1 - Tamoxifen for early breast cancer

T2 - An overview of the randomised trials

AU - Abe, O.

AU - Abe, R.

AU - Enomoto, K.

AU - Kikuchi, K.

AU - Koyama, H.

AU - Nomura, Y.

AU - Sakai, K.

AU - Sugimachi, K.

AU - Tominaga, T.

AU - Uchino, J.

AU - Yoshida, M.

AU - van de Velde, A. O.

AU - van Dongen, J. A.

AU - Vermorken, J. B.

AU - Giokas, G.

AU - Lissaios, B.

AU - Harvey, V. J.

AU - Holdaway, T. M.

AU - Kay, R. G.

AU - Mason, B. H.

AU - Coates, A.

AU - Forbes, J. F.

AU - Focan, C.

AU - Lobelle, J. P.

AU - Peek, U.

AU - Oates, G. D.

AU - Powell, J.

AU - Durand, M.

AU - Mauriac, L.

AU - Bartholomeus, S.

AU - Piccart, M. J.

AU - Gelman, R. S.

AU - Harris, J. R.

AU - Shapiro, C. L.

AU - Hancock, A. K.

AU - Masood, M. B.

AU - Parker, D.

AU - Price, J. J.

AU - Jackson, S.

AU - Ragaz, J.

AU - Delozier, T.

AU - Macé-Lesec'h, J.

AU - Haybittle, J. L.

AU - Cirrincione, C.

AU - Henderson, I. C.

AU - Korzun, A.

AU - Weiss, R. B.

AU - Wood, W. C.

AU - Baum, M.

AU - Houghton, J.

AU - Riley, D.

AU - Dent, D. M.

AU - Gudgeon, C. A.

AU - Hacking, A.

AU - Horgan, K.

AU - Hughes, L.

AU - Stewart, H. J.

AU - Gordon, N. H.

AU - Davis, H. L.

AU - Romestaing, P.

AU - Lehingue, Y.

AU - Owen, J. R.

AU - Meier, P.

AU - Howell, A.

AU - Ribeiro, G. G.

AU - Swindell, R.

AU - Albano, J.

AU - de Oliveira, C. F.

AU - Gervásio, H.

AU - Gordilho, J.

AU - Carstensen, B.

AU - Palshof, T.

AU - Johansen, H.

AU - Korzeniowski, S.

AU - Skolyszewski, J.

AU - Portnoj, S. M.

AU - Andersen, K. W.

AU - Axelsson, C. K.

AU - Blichert-Toft, M.

AU - Mouridsen, H. T.

AU - Overgaard, M.

AU - Rose, C.

AU - Corcoran, N.

AU - Trampisch, H. J.

AU - Comis, R. L.

AU - Davidson, N. E.

AU - Gray, R.

AU - Robert, N.

AU - Tormey, D. C.

AU - Wood, W.

AU - Rossbach, J.

AU - Bijnens, L.

AU - van de Velde, C.

AU - Cunningham, M. P.

AU - Bastert, G.

AU - Rauschecker, H.

AU - Sauer, R.

AU - Sauerbrei, W.

AU - Schauer, A.

AU - Schumacher, M.

AU - de Schryver, A.

AU - Belfiglio, M.

AU - Mari, E.

AU - Nicolucci, A.

AU - Scorpiglione, N.

AU - Yosef, H. M A

AU - McArdle, C. S.

AU - Smith, D. C.

AU - Lara, P. C.

AU - Boccardo, F.

AU - Rubagotti, A.

AU - Erazo, A.

AU - Medina, J. Y.

AU - Izuo, M.

AU - Morishita, Y.

AU - Bentley, A.

AU - Doran, Z.

AU - Fentiman, I. S.

AU - Hayward, J. L.

AU - Rubens, R. D.

AU - Kaufmann, M.

AU - Jonat, W.

AU - von Fournier, D.

AU - Kaufmann, M.

AU - Fountzilas, G.

AU - Klefstrom, P.

AU - Blomqvist, C.

AU - Cuzick, J.

AU - Margreiter, R.

AU - Castiglione, M.

AU - Cavalli, F.

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 - Coombes, R. C.

AU - Marty, M.

AU - Borovik, R.

AU - Brufman, G.

AU - Hayat, H.

AU - Robinson, E.

AU - Wigler, N.

AU - Pannuti, F.

AU - Takashima, S.

AU - Yasutomi, T.

AU - Sonoo, H.

AU - Yamashita, J.

AU - Ogawa, M.

AU - Nomura, Y.

AU - Hupperets, P. S G J

AU - Bonte, J.

AU - Tengrup, I.

AU - Tennvall-Nittby, L.

AU - Martin, P.

AU - Romain, S.

AU - Ahmann, D.

AU - Schaid, D. J.

AU - Buzdar, A. U.

AU - Smith, T.

AU - Hakes, T.

AU - Norton, L.

AU - Wittes, R.

AU - de la Huerta, R.

AU - Sainz, M. G.

AU - Bonadonna, G.

AU - del Vecchio, M.

AU - Valagussa, P.

AU - Veronesi, U.

AU - Dubois, J. B.

AU - Bianco, A. R.

AU - Lippman, M. E.

AU - Pierce, L. J.

AU - Simon, R.

AU - Steinberg, S. M.

AU - Myles, J. D.

AU - Pater, J. L.

AU - Pritchard, K. I.

AU - Anderson, S.

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 - Larsson, L. G.

AU - Lythgoe, J. P.

AU - Swindell, R.

AU - Kissin, M.

AU - Hannisdal, E.

AU - Varhaug, J. E.

AU - Nissen-Meyer, R.

AU - Blamey, R. W.

AU - Mitchell, A. K.

AU - Robertson, J. F R

AU - Nakamura, Y.

AU - Mathé, G.

AU - Misset, J. L.

AU - Abu-Zahra, H. T.

AU - Clarke, E. A.

AU - McLaughlin, J. R.

AU - Clark, R. M.

AU - Levine, M.

AU - Morimoto, K.

AU - Sawa, K.

AU - Takatsuka, Y.

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PY - 1998/5/16

Y1 - 1998/5/16

N2 - Background: There have been many randomised trials of adjuvant tamoxifen among women with early breast cancer, and an updated overview of their results is presented. Methods: In 1995, information was sought on each woman in any randomised trial that began before 1990 of adjuvant tamoxifen versus no tamoxifen before recurrence. Information was obtained and analysed centrally on each of 37,000 women in 55 such trials, comprising about 87% of the worldwide evidence. Compared with the previous such overview, this approximately doubles the amount of evidence from trials of about 5 years of tamoxifen and, taking all trials together, on events occurring more than 5 years after randomisation. Findings: Nearly 8000 of the women had a low, or zero, level of the oestrogen-receptor protein (ER) measured in their primary tumour. Among them, the overall effects of tamoxifen appeared to be small, and subsequent analyses of recurrence and total mortality are restricted to the remaining women (18,000 with ER-positive tumours, plus nearly 12,000 more with untested tumours, of which an estimated 8000 would have been ER-positive). For trials of 1 year, 2 years, and about 5 years of adjuvant tamoxifen, the proportional recurrence reductions produced among these 30,000 women during about 10 years of follow-up were 21% (SD 3), 29% (SD 2), and 47% (SD 3), respectively, with a highly significant trend towards greater effect with longer treatment (χ1 2 = 52.0, 2p <0.00001). The corresponding proportional mortality reductions were 12% (SD 3), 17% (SD 3), and 26% (SD 4), respectively, and again the test for trend was significant (χ1 2 = 8.8) 2p = 0.003). The absolute improvement in recurrence was greater during the first 5 years, whereas the improvement in survival grew steadily larger throughout the first 10 years. The proportional mortality reductions were similar for women with node-positive and node-negative disease, but the absolute mortality reductions were greater in node-positive women. In the trials of about 5 years of adjuvant tamoxifen the absolute improvements in 10-year survival were 10.9% (SD 2.5) for node-positive (61.4% vs 50.5% survival, 2p <0.00001) and 5.6% (SD 1.3) for node-negative (78.9% vs 73.3% survival, 2p <0.00001). These benefits appeared to be largely irrespective of age, menopausal status, daily tamoxifen dose (which was generally 20 mg), and of whether chemotherapy had been given to both groups. In terms of other outcomes among all women studied (ie, including those with 'ER-poor' tumours), the proportional reductions in contralateral breast cancer were 13% (SD 13), 26% (SD 9), and 47% (SD 9) in the trials of 1, 2, or about 5 years of adjuvant tamoxifen. The incidence of endometrial cancer was approximately doubled in trials of 1 or 2 years of tamoxifen and approximately quadrupled in trials of 5 years of tamoxifen (although the number of cases was small and these ratios were not significantly different from each other). The absolute decrease in contralateral breast cancer was about twice as large as the absolute increase in the incidence of endometrial cancer. Tamoxifen had no apparent effect on the incidence of colorectal cancer or, after exclusion of deaths from breast or endometrial cancer, on any of the other main categories of cause of death (total nearly 2000 such deaths; overall relative risk 0.99 [SD 0.05]). Interpretation: For women with tumours that have been reliably shown to be ER-negative, adjuvant tamoxifen remains a matter for research. However, some years of adjuvant tamoxifen treatment substantially improves the 10-year survival of women with ER-positive tumours and of women whose tumours are of unknown ER status, with the proportional reductions in breast cancer recurrence and in mortality appearing to be largely unaffected by other patient characteristics or treatments.

AB - Background: There have been many randomised trials of adjuvant tamoxifen among women with early breast cancer, and an updated overview of their results is presented. Methods: In 1995, information was sought on each woman in any randomised trial that began before 1990 of adjuvant tamoxifen versus no tamoxifen before recurrence. Information was obtained and analysed centrally on each of 37,000 women in 55 such trials, comprising about 87% of the worldwide evidence. Compared with the previous such overview, this approximately doubles the amount of evidence from trials of about 5 years of tamoxifen and, taking all trials together, on events occurring more than 5 years after randomisation. Findings: Nearly 8000 of the women had a low, or zero, level of the oestrogen-receptor protein (ER) measured in their primary tumour. Among them, the overall effects of tamoxifen appeared to be small, and subsequent analyses of recurrence and total mortality are restricted to the remaining women (18,000 with ER-positive tumours, plus nearly 12,000 more with untested tumours, of which an estimated 8000 would have been ER-positive). For trials of 1 year, 2 years, and about 5 years of adjuvant tamoxifen, the proportional recurrence reductions produced among these 30,000 women during about 10 years of follow-up were 21% (SD 3), 29% (SD 2), and 47% (SD 3), respectively, with a highly significant trend towards greater effect with longer treatment (χ1 2 = 52.0, 2p <0.00001). The corresponding proportional mortality reductions were 12% (SD 3), 17% (SD 3), and 26% (SD 4), respectively, and again the test for trend was significant (χ1 2 = 8.8) 2p = 0.003). The absolute improvement in recurrence was greater during the first 5 years, whereas the improvement in survival grew steadily larger throughout the first 10 years. The proportional mortality reductions were similar for women with node-positive and node-negative disease, but the absolute mortality reductions were greater in node-positive women. In the trials of about 5 years of adjuvant tamoxifen the absolute improvements in 10-year survival were 10.9% (SD 2.5) for node-positive (61.4% vs 50.5% survival, 2p <0.00001) and 5.6% (SD 1.3) for node-negative (78.9% vs 73.3% survival, 2p <0.00001). These benefits appeared to be largely irrespective of age, menopausal status, daily tamoxifen dose (which was generally 20 mg), and of whether chemotherapy had been given to both groups. In terms of other outcomes among all women studied (ie, including those with 'ER-poor' tumours), the proportional reductions in contralateral breast cancer were 13% (SD 13), 26% (SD 9), and 47% (SD 9) in the trials of 1, 2, or about 5 years of adjuvant tamoxifen. The incidence of endometrial cancer was approximately doubled in trials of 1 or 2 years of tamoxifen and approximately quadrupled in trials of 5 years of tamoxifen (although the number of cases was small and these ratios were not significantly different from each other). The absolute decrease in contralateral breast cancer was about twice as large as the absolute increase in the incidence of endometrial cancer. Tamoxifen had no apparent effect on the incidence of colorectal cancer or, after exclusion of deaths from breast or endometrial cancer, on any of the other main categories of cause of death (total nearly 2000 such deaths; overall relative risk 0.99 [SD 0.05]). Interpretation: For women with tumours that have been reliably shown to be ER-negative, adjuvant tamoxifen remains a matter for research. However, some years of adjuvant tamoxifen treatment substantially improves the 10-year survival of women with ER-positive tumours and of women whose tumours are of unknown ER status, with the proportional reductions in breast cancer recurrence and in mortality appearing to be largely unaffected by other patient characteristics or treatments.

UR - http://www.scopus.com/inward/record.url?scp=0032537396&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032537396&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(97)11423-4

DO - 10.1016/S0140-6736(97)11423-4

M3 - Article

C2 - 9605801

AN - SCOPUS:0032537396

VL - 351

SP - 1451

EP - 1467

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9114

ER -