Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer

Long-term follow-up of the BiG 1-98 trial

BIG 1-98 Collaborative Group and the International Breast Cancer Study Group

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE: Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. PATIENTS AND METHODS: BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. RESULTS: Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and . 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. CONCLUSION: Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalJournal of Clinical Oncology
Volume37
Issue number2
DOIs
Publication statusPublished - Jan 10 2019

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letrozole
Tamoxifen
Hormones
Breast Neoplasms
Disease-Free Survival
Registries
Breast
Intention to Treat Analysis
Denmark
Natural History
Arm
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer : Long-term follow-up of the BiG 1-98 trial. / BIG 1-98 Collaborative Group and the International Breast Cancer Study Group.

In: Journal of Clinical Oncology, Vol. 37, No. 2, 10.01.2019, p. 105-114.

Research output: Contribution to journalArticle

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title = "Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer: Long-term follow-up of the BiG 1-98 trial",
abstract = "PURPOSE: Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. PATIENTS AND METHODS: BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. RESULTS: Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86{\%}) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9{\%} relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95{\%} CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and . 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. CONCLUSION: Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.",
author = "{BIG 1-98 Collaborative Group and the International Breast Cancer Study Group} and Thomas Ruhstaller and Anita Giobbie-Hurder and Marco Colleoni and Jensen, {Maj Britt} and Bent Ejlertsen and {De Azambuja}, Evandro and Patrick Neven and Istv{\'a}n L{\'a}ng and Jakobsen, {Erik Hugger} and Laurence Gladieff and Herv{\'e} Bonnefoi and Harvey, {Vernon J.} and Simon Spazzapan and Carlo Tondini and {Del Mastro}, Lucia and Corinne Veyret and Edda Simoncini and Lorenzo Gianni and Christoph Rochlitz and Elena Kralidis and Khalil Zaman and Jacek Jassem and Martine Piccart-Gebhart and {Di Leo}, Angelo and Gelber, {Richard D.} and Coates, {Alan S.} and Aron Goldhirsch and Beat Th{\"u}rlimann and Regan, {Meredith M.}",
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T1 - Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer

T2 - Long-term follow-up of the BiG 1-98 trial

AU - BIG 1-98 Collaborative Group and the International Breast Cancer Study Group

AU - Ruhstaller, Thomas

AU - Giobbie-Hurder, Anita

AU - Colleoni, Marco

AU - Jensen, Maj Britt

AU - Ejlertsen, Bent

AU - De Azambuja, Evandro

AU - Neven, Patrick

AU - Láng, István

AU - Jakobsen, Erik Hugger

AU - Gladieff, Laurence

AU - Bonnefoi, Hervé

AU - Harvey, Vernon J.

AU - Spazzapan, Simon

AU - Tondini, Carlo

AU - Del Mastro, Lucia

AU - Veyret, Corinne

AU - Simoncini, Edda

AU - Gianni, Lorenzo

AU - Rochlitz, Christoph

AU - Kralidis, Elena

AU - Zaman, Khalil

AU - Jassem, Jacek

AU - Piccart-Gebhart, Martine

AU - Di Leo, Angelo

AU - Gelber, Richard D.

AU - Coates, Alan S.

AU - Goldhirsch, Aron

AU - Thürlimann, Beat

AU - Regan, Meredith M.

PY - 2019/1/10

Y1 - 2019/1/10

N2 - PURPOSE: Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. PATIENTS AND METHODS: BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. RESULTS: Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and . 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. CONCLUSION: Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

AB - PURPOSE: Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. PATIENTS AND METHODS: BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. RESULTS: Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and . 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. CONCLUSION: Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

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