Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer

Henning Mouridsen, Anita Giobbie-Hurder, Aron Goldhirsch, Beat Thürlimann, Robert Paridaens, Ian Smith, Louis Mauriac, John F. Forbes, Karen N. Price, Meredith M. Regan, Richard D. Gelber, Alan S. Coates

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS: In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor- positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS: At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a non-significant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P = 0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)

Original languageEnglish
Pages (from-to)766-776
Number of pages11
JournalNew England Journal of Medicine
Volume361
Issue number8
DOIs
Publication statusPublished - Aug 20 2009

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letrozole
Tamoxifen
Breast Neoplasms
Therapeutics
Disease-Free Survival
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., Thürlimann, B., Paridaens, R., Smith, I., ... Coates, A. S. (2009). Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. New England Journal of Medicine, 361(8), 766-776. https://doi.org/10.1056/NEJMoa0810818

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. / Mouridsen, Henning; Giobbie-Hurder, Anita; Goldhirsch, Aron; Thürlimann, Beat; Paridaens, Robert; Smith, Ian; Mauriac, Louis; Forbes, John F.; Price, Karen N.; Regan, Meredith M.; Gelber, Richard D.; Coates, Alan S.

In: New England Journal of Medicine, Vol. 361, No. 8, 20.08.2009, p. 766-776.

Research output: Contribution to journalArticle

Mouridsen, H, Giobbie-Hurder, A, Goldhirsch, A, Thürlimann, B, Paridaens, R, Smith, I, Mauriac, L, Forbes, JF, Price, KN, Regan, MM, Gelber, RD & Coates, AS 2009, 'Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer', New England Journal of Medicine, vol. 361, no. 8, pp. 766-776. https://doi.org/10.1056/NEJMoa0810818
Mouridsen, Henning ; Giobbie-Hurder, Anita ; Goldhirsch, Aron ; Thürlimann, Beat ; Paridaens, Robert ; Smith, Ian ; Mauriac, Louis ; Forbes, John F. ; Price, Karen N. ; Regan, Meredith M. ; Gelber, Richard D. ; Coates, Alan S. / Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. In: New England Journal of Medicine. 2009 ; Vol. 361, No. 8. pp. 766-776.
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abstract = "BACKGROUND: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS: In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor- positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS: At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99{\%} confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99{\%} CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a non-significant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95{\%} CI, 0.75 to 1.02; P = 0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)",
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AU - Thürlimann, Beat

AU - Paridaens, Robert

AU - Smith, Ian

AU - Mauriac, Louis

AU - Forbes, John F.

AU - Price, Karen N.

AU - Regan, Meredith M.

AU - Gelber, Richard D.

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N2 - BACKGROUND: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS: In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor- positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS: At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a non-significant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P = 0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)

AB - BACKGROUND: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS: In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor- positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS: At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a non-significant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P = 0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)

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