Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated findings from NCIC CTG MA.17

Paul E. Goss, James N. Ingle, Silvana Martino, Nicholas J. Robert, Hyman B. Muss, Martine J. Piccart, Monica Castiglione, Dongsheng Tu, Lois E. Shepherd, Kathleen I. Pritchard, Robert B Livingston, Nancy E. Davidson, Larry Norton, Edith A. Perez, Jeffrey S. Abrams, David A. Cameron, Michael J. Palmer, Joseph L. Pater

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Abstract

Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: Hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients.

Original languageEnglish (US)
Pages (from-to)1262-1271
Number of pages10
JournalJournal of the National Cancer Institute
Volume97
Issue number17
DOIs
StatePublished - Sep 7 2005
Externally publishedYes

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letrozole
Tamoxifen
Disease-Free Survival
Breast Neoplasms
Survival
Confidence Intervals
Placebos
Therapeutics
Recurrence
Incidence
Lymph Nodes
Aromatase Inhibitors
Poisons
Bone Fractures
Kaplan-Meier Estimate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer : Updated findings from NCIC CTG MA.17. / Goss, Paul E.; Ingle, James N.; Martino, Silvana; Robert, Nicholas J.; Muss, Hyman B.; Piccart, Martine J.; Castiglione, Monica; Tu, Dongsheng; Shepherd, Lois E.; Pritchard, Kathleen I.; Livingston, Robert B; Davidson, Nancy E.; Norton, Larry; Perez, Edith A.; Abrams, Jeffrey S.; Cameron, David A.; Palmer, Michael J.; Pater, Joseph L.

In: Journal of the National Cancer Institute, Vol. 97, No. 17, 07.09.2005, p. 1262-1271.

Research output: Contribution to journalArticle

Goss, PE, Ingle, JN, Martino, S, Robert, NJ, Muss, HB, Piccart, MJ, Castiglione, M, Tu, D, Shepherd, LE, Pritchard, KI, Livingston, RB, Davidson, NE, Norton, L, Perez, EA, Abrams, JS, Cameron, DA, Palmer, MJ & Pater, JL 2005, 'Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated findings from NCIC CTG MA.17', Journal of the National Cancer Institute, vol. 97, no. 17, pp. 1262-1271. https://doi.org/10.1093/jnci/dji250
Goss, Paul E. ; Ingle, James N. ; Martino, Silvana ; Robert, Nicholas J. ; Muss, Hyman B. ; Piccart, Martine J. ; Castiglione, Monica ; Tu, Dongsheng ; Shepherd, Lois E. ; Pritchard, Kathleen I. ; Livingston, Robert B ; Davidson, Nancy E. ; Norton, Larry ; Perez, Edith A. ; Abrams, Jeffrey S. ; Cameron, David A. ; Palmer, Michael J. ; Pater, Joseph L. / Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer : Updated findings from NCIC CTG MA.17. In: Journal of the National Cancer Institute. 2005 ; Vol. 97, No. 17. pp. 1262-1271.
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title = "Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated findings from NCIC CTG MA.17",
abstract = "Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: Hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95{\%} confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95{\%} CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95{\%} CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95{\%} CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients.",
author = "Goss, {Paul E.} and Ingle, {James N.} and Silvana Martino and Robert, {Nicholas J.} and Muss, {Hyman B.} and Piccart, {Martine J.} and Monica Castiglione and Dongsheng Tu and Shepherd, {Lois E.} and Pritchard, {Kathleen I.} and Livingston, {Robert B} and Davidson, {Nancy E.} and Larry Norton and Perez, {Edith A.} and Abrams, {Jeffrey S.} and Cameron, {David A.} and Palmer, {Michael J.} and Pater, {Joseph L.}",
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TY - JOUR

T1 - Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer

T2 - Updated findings from NCIC CTG MA.17

AU - Goss, Paul E.

AU - Ingle, James N.

AU - Martino, Silvana

AU - Robert, Nicholas J.

AU - Muss, Hyman B.

AU - Piccart, Martine J.

AU - Castiglione, Monica

AU - Tu, Dongsheng

AU - Shepherd, Lois E.

AU - Pritchard, Kathleen I.

AU - Livingston, Robert B

AU - Davidson, Nancy E.

AU - Norton, Larry

AU - Perez, Edith A.

AU - Abrams, Jeffrey S.

AU - Cameron, David A.

AU - Palmer, Michael J.

AU - Pater, Joseph L.

PY - 2005/9/7

Y1 - 2005/9/7

N2 - Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: Hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients.

AB - Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: Hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients.

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