Unpacking Trastuzumab-Induced Cardiomyopathy: A Cardiac Conundrum

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

- authors should include tables which should gather the main findings from the literature in order to provide a comprehensive evaluation to the readers.

- lines 97-98 make no sense as the sentence seems a title (Unmasking the Potential for Cardiotoxicity with Immune Checkpoint Inhibitors and 97 Trastuzumab). It would be better to delete "Review" and shorten this sentence in order to create a dedicated title for this section.

- the use of LVEF for evaluating the impact of these drugs on cardiac structures is really limiting and out-of-date. Authors should discuss about subclinical alterations on cardiac cells which could be outlined by more advances imaging techniques. Please update.

- there is no mention to therapies and pharmacological approaches to cardiotoxicity. This limits the novelty of the paper. Please update.

- there is no mention to a practical, clinical pathway for evaluating and managing these patients. This is a fundamental part for the promotion of this paper, otherwise it contains redundant parts as compared to the literature.

Author Response

Thank you very much for reviewing my article. I truly appreciate your feedback. I have revised the English language as recommended and implemented the suggested changes to lines 97 and 98. Additionally, I have enhanced the overall language proficiency throughout the article in accordance with my attending professor's guidance as per your recommendations.

Reviewer 2 Report

Comments and Suggestions for Authors

The review paper by Peshin S, et al. aims, in the authors words, to provide a comprehensive overview of trastuzumab-induced cardiomyopathy offering insights into the mechanisms through which trastuzumab exerts its cardiotoxic effects, clinical manifestations, diagnostic strategies and potential cardioprotective interventions.

There are some lines of suggested therapy or recommendations but mostly the paper summarizes the many clinical issues involving therapy with trastuzumab that need investigation and research. So in that sense the paper raises the well-known issue of trastuzumab-associated cardiotoxicity and is basically a blueprint of a list of the current clinical problems in need of future studies.

I have to admit that I am not an expert in the field of onco-cardiology but suspect that the paper is not too original or innovative in its content.

Comments on the Quality of English Language

The paper needs extensive English editing

Author Response

Thank you immensely for reviewing my article. I sincerely appreciate your invaluable feedback. Furthermore, I have addressed your recommendations to improve the overall English proficiency and implemented the suggested changes accordingly.

Reviewer 3 Report

Comments and Suggestions for Authors

Peshin et al wrote an interesting review on Trastuzumab-induced cardiomyopathy. Authors explained very well the mechanisms through which Trastuzumab exerts its cardiotoxic effects and described the clinical manifestations of this toxicity.

I found the paper intetesting and well written, otherwise it deserves some comments.

1)      As the authors correctly point out, the clinical utility of assessing left ventricular (LV) systolic function in women with early-stage breast cancer receiving trastuzumab-based therapy is still under debate. Additionally, the relationship between asymptomatic LV systolic dysfunction and the onset of heart failure in these patients remains unclear.

It would be interesting for the authors to report the state of knowledge on cardiotoxicity in other chemotherapeutic agents that have been used for a longer period. Although the authors briefly mentioned this information on page 5, I believe it is important to expand this section. What are the recommended cardiac evaluations for patients undergoing chemotherapy? When should treatment be withdrawn? Do we have any data on the role of heart failure therapies, such as gliflozins, in these patients?

2)      The authors stated that “the rates of both symptomatic and asymptomatic LVEF decline are remarkably low.” It would be interesting to have more detailed information about this point.

3)      The authors mentioned several times that randomized trials on the cardiotoxicity effects in patients with normal systolic function are lacking. It would be useful to provide a table summarizing the existing studies on the cardiotoxicity of chemotherapeutic agents.

4)      Finally, for a patient undergoing therapy with trastuzumab, what potential protocol for cardiac evaluation before, during, and after therapy should the authors suggest based on the existing data on the cardiotoxicity of this drug?

Author Response

Thank you immensely for reviewing my article. I sincerely appreciate your invaluable feedback. Furthermore, I have addressed your recommendations to improve the overall English proficiency and implemented the suggested changes accordingly.

To clarify, this review article focuses on trastuzumab and its impact, which constitutes our primary objective. Additionally, I am planning to write a separate review article that examines different medications, combining all HER2-positive cancers and the cardiotoxic effects of various drugs.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

authors well addressed previous comments. The paper improved very much

Reviewer 2 Report

Comments and Suggestions for Authors

This revised review paper by Peshin S, et al. aims, in the authors words, to provide a comprehensive overview of trastuzumab-induced cardiomyopathy offering insights into the mechanisms through which trastuzumab exerts its cardiotoxic effects, clinical manifestations, diagnostic strategies and potential cardioprotective interventions.

Minimal comments

Page 4: It would be helpful for the sake of interested readers to spell out the acronyms in the sentence “BCIRG 006 demonstrated higher rates of CHF in the AC-DH group (2.0%) compared to the AC-D group (0.7%) or TCH group (0.4%).”

English style much improved compared to that of the first version

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors, I think the paper improved a lot after revision