by Laura Pala,
Tommaso De Pas, Eleonora Pagan, Isabella Sala, Chiara Catania, Emma Zattarin,
Paolo Arnone, Massimo M. Grassi, Marco Colleoni, Antonio C. Wolff, Javier
Cortes, Martine Piccart, Richard D. Gelber, Giuseppe Viale, Vincenzo Bagnardi,
Fabio Conforti
The Breast: Published: March 01, 2023
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.
