Title: Optimal Extension Time after Initial Endocrine Therapy for Postmenopausal Hormone
Receptor-Positive Early-stage Breast Cancer: A systematic review and meta-analysis
Version: 1 Date: 26 May 2024
Reviewer's report:
Ying Zhang etc. conducted a systematic review and meta-analysis on extended aromatase
inhibitors after the recommended initial 5-year endocrine therapy. My primary concern is the
need for the authors to clarify the aim of their study. It is unclear whether they intend to compare
the continuation of aromatase inhibitors (AIs) for 5-6 years versus 2-3 years after an initial 5-
year treatment or to compare patients continuing AIs after a 5-year initial treatment with those
who did not continue AIs after the initial 5-year treatment. The study aims of the included four
RCTs seem to be a mix of these two objectives.
Another significant issue is the apparent plagiarism in line 226. Do not copy and paste the
limitations section from the study (PMID: 35980311), as it is not relevant at all, and plagiarism
is a serious concern.
Other comments include:
1) Line 84: What is obvious bias? Please list any example you identified in the literature research.
2) Line 85: Point (2) seems repetitive with Point (5) in the inclusion criteria. Please consolidate
or eliminate the redundancy to ensure clarity.
3) Line 102: How about “local recurrence, distant metastasis, 2nd primary breast cancer”
mentioned in the abstract? Are they secondary endpoints you measured?
4) Line 115: These outcomes (local recurrence, distant metastasis, second primary breast cancer,
all-cause mortality) are all time-to-event data, why not use HR?
5) Figure 1: Please specify what “b. advanced endocrine therapy” means in Figure 1.
Additionally, the selection process is a little bit hard to follow, the authors set up two different
boxes for exclusion reasons 1) record exclusion because of the following reasons (n=41), 2)
records exclusion that mismatches inclusion and exclusion criteria. However, there is some
overlap between these two boxes. Please set a consistent or more logical inclusion/exclusion
through the whole selection process.
6) Line 141: Majority RCTs also included second primary cancer as DFS, please clarify it.
Besides, outcome definition heterogeneity needs to be assessed between 4 RCTs.
7) Line 146-148: These events are time-to-event data, why not use HR as a measurement? If
RCTs did not report HR of these outcomes, I would suggest not including such outcomes in
this meta-analysis.
8) Line 153: Is it prolonged AI for 5-6 years? Please clarify it.
9) Line 165: Please clarify what kind of sensitivity analysis was conducted in the method part,
and which aspect was considered in order to assess the robustness of your study.
10) Line 170: RRs of AEs were not reported in the RCTs, please clarify the method of calculating
RR in Supplementary Table 2.
11) Supplemental Table 2: Please clarify why the authors used the random effects model for
some outcomes, and the fixed effects model for others.
12) Line 193: In ABCSG-16 AND IDEAL trials, both intervention and control groups extend ET
after an initial 5-6 years, please reconsider the formulation of this sentence. Again, the authors
need to clarify what their research question was, all the study selection process, analysis, and
discussion need to serve their research question.
13) Line 196-198: This sentence is unclear. Patients who completed adjuvant ET for 5 years
after the initial 5-6 years of treatment? Had more AEs or AIs?
14) Line 226-232: Don't copy and paste the limitation section from this study (PMID: 35980311),
and it's not relevant at all. Be serious about plagiarism.