The Significance of Thyroid Hormone Receptors in Breast Cancer: A Hypothesis-Generating Narrative Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a very interesting and relevant paper which I think should be published with some amendments:

Abstract

-         You state that THRbeta is know to have potential prognostic significant in breast cancer but do not give the reason for studying THRalpha also?

-          The title calls this piece of work a narrative review but there is a detailed search strategy that can be replicated – is this not a systematic review of the literature? I think this would be a more robust piece of work if it was a systematic review and you can use the REMARK criteria to critique each study

Introduction/ Methods

-          You state in the introduction that you are only looking at retrospective studies but there does not appear to be a limit on your search criteria for retrospective studies – did you intent this or is it just that all of the studies happened to be retrospective? If you intended just to look at retrospective studies then please say why

Results

-          Table 1 – can you include where the study was performed and what

-          Table S2 – I am not sure why this has been included as a supplementary table, I believe it would benefit from being in the main article. Could you include in the table the method used to measure the biomarker (e.g. IHC). Please also include the manufacturer, concentration of antibody used and incubation time – this would allow for better comparison between studies. It would also be helpful to know WHY these biomarkers were measured in the studies – what was the purpose and could you summarise the results?

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript titled "The Significance of Thyroid Hormone Receptors in Breast Cancer: A Narrative Review" is a comprehensive narrative review focused on the clinical relevance of thyroid hormone receptors (THRs), specifically THRβ, as potential prognostic biomarkers and therapeutic targets in breast cancer (BC). The authors have done an extensive literature search and presented data from various retrospective studies to support their hypothesis. The evidence selected of this manuscript is weak, and the content of this article is also limited. Thus, major revision is recommended. Major issues have been listed as following:

1.     The type of this manuscript should be classified as hypothesis “mini-review” or “hypothesis”, etc, based on its limited content. 

2.     The manuscript presents studies with contrasting findings regarding the localization of THRβ and its association with patient outcomes. It would be beneficial to delve deeper into why these discrepancies exist and what they might imply for future research. 

3.     The manuscript primarily focuses on retrospective studies. Including a discussion on the need for prospective studies to validate the retrospective findings would strengthen the conclusions.

4.     A broader discussion on how these findings fit into the larger landscape of BC research and treatment could provide additional context. 

5.     More emphasis on the biological mechanisms through which THRs influence BC could provide a deeper understanding of the potential therapeutic implications (related figures are also recommended)

6.     The manuscript would benefit from a more detailed discussion on the future research directions, including potential clinical trials and exploration of THRβ as a target for drug development. 

7.     Inclusion of more figures or diagrams summarizing the key findings or illustrating the proposed mechanisms could enhance the readability and appeal of the manuscript.

8.     Can Thyroid Hormone Receptors targeted therapy potentially be applied with immune checkpoint inhibitors? Authors should discuss related mechanisms and clinical potential.

9.     The future research directions and challenges of Thyroid Hormone Receptors targeted therapy should also be discussed. 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

happy to accept