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Meta-Analysis
. 2023 Jun:69:258-264.
doi: 10.1016/j.breast.2023.02.012. Epub 2023 Mar 2.

Tailoring the optimal duration of the extended adjuvant endocrine therapy in patients with early-stage breast cancer. A systematic review and meta-analysis of randomized clinical trials

Laura Pala  1 , Tommaso De Pas  1 , Eleonora Pagan  2 , Isabella Sala  2 , Chiara Catania  1 , Emma Zattarin  1 , Paolo Arnone  3 , Massimo M Grassi  3 , Marco Colleoni  4 , Antonio C Wolff  5 , Javier Cortes  6 , Martine Piccart  7 , Richard D Gelber  8 , Giuseppe Viale  9 , Vincenzo Bagnardi  2 , Fabio Conforti  10
Affiliations
Meta-Analysis

Tailoring the optimal duration of the extended adjuvant endocrine therapy in patients with early-stage breast cancer. A systematic review and meta-analysis of randomized clinical trials

Laura Pala et al. Breast. 2023 Jun.

Abstract

Background: Controversy exists regarding the optimal duration of the extended adjuvant endocrine treatment (ET) in patients with early-stage breast-cancer (eBC). We performed a systematic review and trial-level meta-analysis of all randomized clinical trials (RCTs) comparing a "limited-extended" adjuvant ET (defined as more than 5 but less than 7.5 years of treatment overall) versus a "full-extended" adjuvant ET (defined as more than 7.5 years of treatment overall) in eBC.

Methods: To be eligible, RCTs had to i) compare a "limited-extended" adjuvant ET versus a "full-extended" adjuvant ET in patients with eBC; and ii) report disease-free survival (DFS) hazard ratio (HR) according to the disease nodal-status [i.e., nodal-negative (N-ve) versus nodal-positive (N + ve)]. The primary endpoint was to assess the difference in efficacy of full-versus limited-extended ET, measured in terms of the difference in DFS log-HR, according to the disease nodal-status. Secondary endpoint was the difference in efficacy of full-versus limited-extended ET according to tumor size (i.e., pT1 vs pT2/3/4), histological grade (i.e., G1/G2 vs G3), patients' age (i.e., ≤60 vs > 60 years) and previous type of ET (i.e., aromatase inhibitors vs tamoxifen vs switch strategy).

Results: Three phase III RCTs fulfilled the inclusion criteria. A total of 6689 patients were included in the analysis, of which 3506 (53%) had N + ve disease. The full-extended ET provided no DFS-benefit as compared with the limited-extended ET in patients with N-ve disease (pooled DFS-HR = 1.04, 95%CI: 0.89 to 1.22; I2 = 18%). Conversely, in patients with N + ve disease the full-extended ET significantly improved DFS, with a pooled DFS-HR of 0.85 (95%CI: 0.74 to 0.97; I2 = 0%). There was a significant interaction between the disease nodal-status and the efficacy of the full-versus limited-extended ET (p-heterogeneity = 0.048). The full-extended ET provided no significant DFS-benefit as compared with the limited-extended ET in all the other subgroups analyzed.

Conclusions: Patients with eBC and N + ve disease can obtain a significant DFS-benefit from the full-extended as compared with the limited-extended adjuvant ET.

Keywords: Disease nodal status; Early breast cancer; Extended adjuvant endocrine therapy; meta-analysis.

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Conflict of interest statement

Declaration of competing interest All other authors declare no conflicts of interest. The lead author (FC) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Efficacy of full versus limited extended adjuvant endocrine treatment (ET), in the ITT population (panel A) and by status of lymph nodes disease (panel B).
Fig. 2
Fig. 2
Efficacy of full versus limited extended adjuvant endocrine treatment (ET), according to age at randomization (panel A), tumor size (panel B), histological grade (panel C), and prior endocrine treatment (panel D).
See this image and copyright information in PMC

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