Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer

Erik J Blok,On Behalf Of The Ideal Study Group ,Cornelis J H Van De Velde,Judith R Kroep,Gerrit-Jan Liefers,Johan W R Nortier,Elma Meershoek-Klein Kranenbarg,Caroline M Seynaeve,Hein Putter,Marjolijn Duijm-De Carpentier,Emiel J Th Rutgers

doi:10.1007/s10549-017-4601-1

Abstract

PurposeFor postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy.MethodsIn the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses.ResultsIn node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47–0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38–0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13–1.06), although this additional analysis was underpowered for definite conclusions.ConclusionsThis study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isolated to patients treated with sequential endocrine therapy during the first 5 years and needs validation and long-term follow-up.

Highlights

In hormone receptor-positive (HR+) breast cancer, adjuvant endocrine therapy is used to decrease the risk for recurrence, and improve the overall survival (OS)
Despite the value of adjuvant endocrine therapy, it is known that the risk for recurrence in Hazard ratios (HRs)+ breast cancer remains linear up to at least 15 years after diagnosis prompting to study the value of extended endocrine therapy
Of the 1824 postmenopausal patients enrolled in the IDEAL trial, 1339 were disease free and on letrozole therapy at 2.5 years after randomization, and were eligible for the current analysis

Summary

Introduction

In hormone receptor-positive (HR+) breast cancer, adjuvant endocrine therapy is used to decrease the risk for recurrence, and improve the overall survival (OS). The Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial showed that after 5 and 10 years of follow-up, there was no difference in disease-free survival (DFS) between patients randomized to either tamoxifen followed by exemestane or exemestane monotherapy [1, 2]. After 5 years of tamoxifen, it has been established that extended therapy beyond 5 years leads to a modest reduction in recurrences, but not in overall survival [4, 5] This has been observed for patients with node-positive disease [6]

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Conclusion