Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: A meta-analysis of four randomized trials

J. G M Klijn; R. W. Blamey; F. Boccardo; T. Tominaga; L. Duchateau; R. Sylvester; L. V A M Beex; L. Mauriac; J. A. Van Zijl; C. Veyret; J. Wildiers; J. Jassem; M. Piccart; J. Burghouts; D. Becqaert; C. Seynaeve; F. Mignolet; L. Duchateau; R. Sylvester; M. Namer; J. P. Julien; J. Garcia Conde; M. Dunser; R. Margreiter; T. Tjabbes; K. J. Roozendaal; P. C. Van der Velden; J. W R Nortier; R. Blamey; A. Howell; J. Forbes; M. Kaufmann; B. Nordenskjold; S. Kvinnsland; R. G. Wilson; W. Jonat; U. R. Kleeberg; W. Eiermann; J. Hilfrich; H. K. Weitzel; U. Glas; L. E. Rutqvist; C. Rudenstam; S. Sander; S. Ryden; P. Honsson; P. E. Lonning; L. Loven; I. S. Russell; C. Olweny; J. J. Byrne; R. D. Snyder; A. S. Coates; R. M. Lowenthal; P. N. Jeal; D. N. Dalley; F. Janicke; W. Kleine; R. Th Michel; L. Canobbio; D. Amoroso; A. Rubagotti; C. Bumma; M. D'Aprile; A. De Matteis; A. Di Carlo; G. Francini; R. Petrioli; U. Folco; E. Calligioni; P. Gallotti; M. Lopez; M. Mesiti; P. Pacini; M. Sassi; P. Sismondi; P. Zola; M. Ogita; M. Okazaki; T. Watanabe; T. Satomi; C. Hatazawa; N. Okuyama; T. Koyama; M. Kobayashi; T. Shimizu; T. Tabei; M. Sano; H. Makino; J. Ando; M. Kimura; T. Takeuchi; H. Aoyama; H. Koyama; E. Shin; G. Chou

Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: A meta-analysis of four randomized trials

J. G M Klijn, R. W. Blamey, F. Boccardo, T. Tominaga, L. Duchateau, R. Sylvester, L. V A M Beex, L. Mauriac, J. A. Van Zijl, C. Veyret, J. Wildiers, J. Jassem, M. Piccart, J. Burghouts, D. Becqaert, C. Seynaeve, F. Mignolet, L. Duchateau, R. Sylvester, M. NamerJ. P. Julien, J. Garcia Conde, M. Dunser, R. Margreiter, T. Tjabbes, K. J. Roozendaal, P. C. Van der Velden, J. W R Nortier, R. Blamey, A. Howell, J. Forbes, M. Kaufmann, B. Nordenskjold, S. Kvinnsland, R. G. Wilson, W. Jonat, U. R. Kleeberg, W. Eiermann, J. Hilfrich, H. K. Weitzel, U. Glas, L. E. Rutqvist, C. Rudenstam, S. Sander, S. Ryden, P. Honsson, P. E. Lonning, L. Loven, I. S. Russell, C. Olweny, J. J. Byrne, R. D. Snyder, A. S. Coates, R. M. Lowenthal, P. N. Jeal, D. N. Dalley, F. Janicke, W. Kleine, R. Th Michel, L. Canobbio, D. Amoroso, A. Rubagotti, C. Bumma, M. D'Aprile, A. De Matteis, A. Di Carlo, G. Francini, R. Petrioli, U. Folco, E. Calligioni, P. Gallotti, M. Lopez, M. Mesiti, P. Pacini, M. Sassi, P. Sismondi, P. Zola, M. Ogita, M. Okazaki, T. Watanabe, T. Satomi, C. Hatazawa, N. Okuyama, T. Koyama, M. Kobayashi, T. Shimizu, T. Tabei, M. Sano, H. Makino, J. Ando, M. Kimura, T. Takeuchi, H. Aoyama, H. Koyama, E. Shin, G. Chou

A.O.U. San Martino - IST, Istituto Nazionale Ricerca sul Cancro (GENOVA)

Research output: Contribution to journal › Article

Abstract

Purpose: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tomoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. Patients and Methods: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tomoxifen were identified. Meto-analytic techniques were used to analyze individual patient data from these trials. Results: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] =0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR =0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio =0.67). Conclusion: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.

Original language	English
Pages (from-to)	343-353
Number of pages	11
Journal	Journal of Clinical Oncology
Volume	19
Issue number	2
Publication status	Published - Jan 15 2001

ASJC Scopus subject areas

Cancer Research
Oncology

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Klijn, J. G. M., Blamey, R. W., Boccardo, F., Tominaga, T., Duchateau, L., Sylvester, R., Beex, L. V. A. M., Mauriac, L., Van Zijl, J. A., Veyret, C., Wildiers, J., Jassem, J., Piccart, M., Burghouts, J., Becqaert, D., Seynaeve, C., Mignolet, F., Duchateau, L., Sylvester, R., ... Chou, G. (2001). Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: A meta-analysis of four randomized trials. Journal of Clinical Oncology, 19(2), 343-353.

Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer : A meta-analysis of four randomized trials. / Klijn, J. G M; Blamey, R. W.; Boccardo, F.; Tominaga, T.; Duchateau, L.; Sylvester, R.; Beex, L. V A M; Mauriac, L.; Van Zijl, J. A.; Veyret, C.; Wildiers, J.; Jassem, J.; Piccart, M.; Burghouts, J.; Becqaert, D.; Seynaeve, C.; Mignolet, F.; Duchateau, L.; Sylvester, R.; Namer, M.; Julien, J. P.; Garcia Conde, J.; Dunser, M.; Margreiter, R.; Tjabbes, T.; Roozendaal, K. J.; Van der Velden, P. C.; Nortier, J. W R; Blamey, R.; Howell, A.; Forbes, J.; Kaufmann, M.; Nordenskjold, B.; Kvinnsland, S.; Wilson, R. G.; Jonat, W.; Kleeberg, U. R.; Eiermann, W.; Hilfrich, J.; Weitzel, H. K.; Glas, U.; Rutqvist, L. E.; Rudenstam, C.; Sander, S.; Ryden, S.; Honsson, P.; Lonning, P. E.; Loven, L.; Russell, I. S.; Olweny, C.; Byrne, J. J.; Snyder, R. D.; Coates, A. S.; Lowenthal, R. M.; Jeal, P. N.; Dalley, D. N.; Janicke, F.; Kleine, W.; Michel, R. Th; Canobbio, L.; Amoroso, D.; Rubagotti, A.; Bumma, C.; D'Aprile, M.; De Matteis, A.; Di Carlo, A.; Francini, G.; Petrioli, R.; Folco, U.; Calligioni, E.; Gallotti, P.; Lopez, M.; Mesiti, M.; Pacini, P.; Sassi, M.; Sismondi, P.; Zola, P.; Ogita, M.; Okazaki, M.; Watanabe, T.; Satomi, T.; Hatazawa, C.; Okuyama, N.; Koyama, T.; Kobayashi, M.; Shimizu, T.; Tabei, T.; Sano, M.; Makino, H.; Ando, J.; Kimura, M.; Takeuchi, T.; Aoyama, H.; Koyama, H.; Shin, E.; Chou, G.

In: Journal of Clinical Oncology, Vol. 19, No. 2, 15.01.2001, p. 343-353.

Research output: Contribution to journal › Article

Klijn, JGM, Blamey, RW, Boccardo, F, Tominaga, T, Duchateau, L, Sylvester, R, Beex, LVAM, Mauriac, L, Van Zijl, JA, Veyret, C, Wildiers, J, Jassem, J, Piccart, M, Burghouts, J, Becqaert, D, Seynaeve, C, Mignolet, F, Duchateau, L, Sylvester, R, Namer, M, Julien, JP, Garcia Conde, J, Dunser, M, Margreiter, R, Tjabbes, T, Roozendaal, KJ, Van der Velden, PC, Nortier, JWR, Blamey, R, Howell, A, Forbes, J, Kaufmann, M, Nordenskjold, B, Kvinnsland, S, Wilson, RG, Jonat, W, Kleeberg, UR, Eiermann, W, Hilfrich, J, Weitzel, HK, Glas, U, Rutqvist, LE, Rudenstam, C, Sander, S, Ryden, S, Honsson, P, Lonning, PE, Loven, L, Russell, IS, Olweny, C, Byrne, JJ, Snyder, RD, Coates, AS, Lowenthal, RM, Jeal, PN, Dalley, DN, Janicke, F, Kleine, W, Michel, RT, Canobbio, L, Amoroso, D, Rubagotti, A, Bumma, C, D'Aprile, M, De Matteis, A, Di Carlo, A, Francini, G, Petrioli, R, Folco, U, Calligioni, E, Gallotti, P, Lopez, M, Mesiti, M, Pacini, P, Sassi, M, Sismondi, P, Zola, P, Ogita, M, Okazaki, M, Watanabe, T, Satomi, T, Hatazawa, C, Okuyama, N, Koyama, T, Kobayashi, M, Shimizu, T, Tabei, T, Sano, M, Makino, H, Ando, J, Kimura, M, Takeuchi, T, Aoyama, H, Koyama, H, Shin, E & Chou, G 2001, 'Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: A meta-analysis of four randomized trials', Journal of Clinical Oncology, vol. 19, no. 2, pp. 343-353.

Klijn, J. G M ; Blamey, R. W. ; Boccardo, F. ; Tominaga, T. ; Duchateau, L. ; Sylvester, R. ; Beex, L. V A M ; Mauriac, L. ; Van Zijl, J. A. ; Veyret, C. ; Wildiers, J. ; Jassem, J. ; Piccart, M. ; Burghouts, J. ; Becqaert, D. ; Seynaeve, C. ; Mignolet, F. ; Duchateau, L. ; Sylvester, R. ; Namer, M. ; Julien, J. P. ; Garcia Conde, J. ; Dunser, M. ; Margreiter, R. ; Tjabbes, T. ; Roozendaal, K. J. ; Van der Velden, P. C. ; Nortier, J. W R ; Blamey, R. ; Howell, A. ; Forbes, J. ; Kaufmann, M. ; Nordenskjold, B. ; Kvinnsland, S. ; Wilson, R. G. ; Jonat, W. ; Kleeberg, U. R. ; Eiermann, W. ; Hilfrich, J. ; Weitzel, H. K. ; Glas, U. ; Rutqvist, L. E. ; Rudenstam, C. ; Sander, S. ; Ryden, S. ; Honsson, P. ; Lonning, P. E. ; Loven, L. ; Russell, I. S. ; Olweny, C. ; Byrne, J. J. ; Snyder, R. D. ; Coates, A. S. ; Lowenthal, R. M. ; Jeal, P. N. ; Dalley, D. N. ; Janicke, F. ; Kleine, W. ; Michel, R. Th ; Canobbio, L. ; Amoroso, D. ; Rubagotti, A. ; Bumma, C. ; D'Aprile, M. ; De Matteis, A. ; Di Carlo, A. ; Francini, G. ; Petrioli, R. ; Folco, U. ; Calligioni, E. ; Gallotti, P. ; Lopez, M. ; Mesiti, M. ; Pacini, P. ; Sassi, M. ; Sismondi, P. ; Zola, P. ; Ogita, M. ; Okazaki, M. ; Watanabe, T. ; Satomi, T. ; Hatazawa, C. ; Okuyama, N. ; Koyama, T. ; Kobayashi, M. ; Shimizu, T. ; Tabei, T. ; Sano, M. ; Makino, H. ; Ando, J. ; Kimura, M. ; Takeuchi, T. ; Aoyama, H. ; Koyama, H. ; Shin, E. ; Chou, G. / Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer : A meta-analysis of four randomized trials. In: Journal of Clinical Oncology. 2001 ; Vol. 19, No. 2. pp. 343-353.

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title = "Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: A meta-analysis of four randomized trials",

abstract = "Purpose: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tomoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. Patients and Methods: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tomoxifen were identified. Meto-analytic techniques were used to analyze individual patient data from these trials. Results: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] =0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR =0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio =0.67). Conclusion: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.",

author = "Klijn, {J. G M} and Blamey, {R. W.} and F. Boccardo and T. Tominaga and L. Duchateau and R. Sylvester and Beex, {L. V A M} and L. Mauriac and {Van Zijl}, {J. A.} and C. Veyret and J. Wildiers and J. Jassem and M. Piccart and J. Burghouts and D. Becqaert and C. Seynaeve and F. Mignolet and L. Duchateau and R. Sylvester and M. Namer and Julien, {J. P.} and {Garcia Conde}, J. and M. Dunser and R. Margreiter and T. Tjabbes and Roozendaal, {K. J.} and {Van der Velden}, {P. C.} and Nortier, {J. W R} and R. Blamey and A. Howell and J. Forbes and M. Kaufmann and B. Nordenskjold and S. Kvinnsland and Wilson, {R. G.} and W. Jonat and Kleeberg, {U. R.} and W. Eiermann and J. Hilfrich and Weitzel, {H. K.} and U. Glas and Rutqvist, {L. E.} and C. Rudenstam and S. Sander and S. Ryden and P. Honsson and Lonning, {P. E.} and L. Loven and Russell, {I. S.} and C. Olweny and Byrne, {J. J.} and Snyder, {R. D.} and Coates, {A. S.} and Lowenthal, {R. M.} and Jeal, {P. N.} and Dalley, {D. N.} and F. Janicke and W. Kleine and Michel, {R. Th} and L. Canobbio and D. Amoroso and A. Rubagotti and C. Bumma and M. D'Aprile and {De Matteis}, A. and {Di Carlo}, A. and G. Francini and R. Petrioli and U. Folco and E. Calligioni and P. Gallotti and M. Lopez and M. Mesiti and P. Pacini and M. Sassi and P. Sismondi and P. Zola and M. Ogita and M. Okazaki and T. Watanabe and T. Satomi and C. Hatazawa and N. Okuyama and T. Koyama and M. Kobayashi and T. Shimizu and T. Tabei and M. Sano and H. Makino and J. Ando and M. Kimura and T. Takeuchi and H. Aoyama and H. Koyama and E. Shin and G. Chou",

year = "2001",

month = jan,

day = "15",

language = "English",

volume = "19",

pages = "343--353",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "2",

}

TY - JOUR

T1 - Combined tamoxifen and luteinuzing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer

T2 - A meta-analysis of four randomized trials

AU - Klijn, J. G M

AU - Blamey, R. W.

AU - Boccardo, F.

AU - Tominaga, T.

AU - Duchateau, L.

AU - Sylvester, R.

AU - Beex, L. V A M

AU - Mauriac, L.

AU - Van Zijl, J. A.

AU - Veyret, C.

AU - Wildiers, J.

AU - Jassem, J.

AU - Piccart, M.

AU - Burghouts, J.

AU - Becqaert, D.

AU - Seynaeve, C.

AU - Mignolet, F.

AU - Duchateau, L.

AU - Sylvester, R.

AU - Namer, M.

AU - Julien, J. P.

AU - Garcia Conde, J.

AU - Dunser, M.

AU - Margreiter, R.

AU - Tjabbes, T.

AU - Roozendaal, K. J.

AU - Van der Velden, P. C.

AU - Nortier, J. W R

AU - Blamey, R.

AU - Howell, A.

AU - Forbes, J.

AU - Kaufmann, M.

AU - Nordenskjold, B.

AU - Kvinnsland, S.

AU - Wilson, R. G.

AU - Jonat, W.

AU - Kleeberg, U. R.

AU - Eiermann, W.

AU - Hilfrich, J.

AU - Weitzel, H. K.

AU - Glas, U.

AU - Rutqvist, L. E.

AU - Rudenstam, C.

AU - Sander, S.

AU - Ryden, S.

AU - Honsson, P.

AU - Lonning, P. E.

AU - Loven, L.

AU - Russell, I. S.

AU - Olweny, C.

AU - Byrne, J. J.

AU - Snyder, R. D.

AU - Coates, A. S.

AU - Lowenthal, R. M.

AU - Jeal, P. N.

AU - Dalley, D. N.

AU - Janicke, F.

AU - Kleine, W.

AU - Michel, R. Th

AU - Canobbio, L.

AU - Amoroso, D.

AU - Rubagotti, A.

AU - Bumma, C.

AU - D'Aprile, M.

AU - De Matteis, A.

AU - Di Carlo, A.

AU - Francini, G.

AU - Petrioli, R.

AU - Folco, U.

AU - Calligioni, E.

AU - Gallotti, P.

AU - Lopez, M.

AU - Mesiti, M.

AU - Pacini, P.

AU - Sassi, M.

AU - Sismondi, P.

AU - Zola, P.

AU - Ogita, M.

AU - Okazaki, M.

AU - Watanabe, T.

AU - Satomi, T.

AU - Hatazawa, C.

AU - Okuyama, N.

AU - Koyama, T.

AU - Kobayashi, M.

AU - Shimizu, T.

AU - Tabei, T.

AU - Sano, M.

AU - Makino, H.

AU - Ando, J.

AU - Kimura, M.

AU - Takeuchi, T.

AU - Aoyama, H.

AU - Koyama, H.

AU - Shin, E.

AU - Chou, G.

PY - 2001/1/15

Y1 - 2001/1/15

N2 - Purpose: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tomoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. Patients and Methods: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tomoxifen were identified. Meto-analytic techniques were used to analyze individual patient data from these trials. Results: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] =0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR =0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio =0.67). Conclusion: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.

AB - Purpose: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tomoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. Patients and Methods: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tomoxifen were identified. Meto-analytic techniques were used to analyze individual patient data from these trials. Results: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] =0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR =0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio =0.67). Conclusion: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.

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UR - http://www.scopus.com/inward/citedby.url?scp=0035862149&partnerID=8YFLogxK

M3 - Article

C2 - 11208825

AN - SCOPUS:0035862149

VL - 19

SP - 343

EP - 353

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 2

ER -