A Prospective Population-Based Study of Cardiovascular Disease Mortality following Treatment for Breast Cancer among Men in the United States, 2000–2019

Round 1

Reviewer 1 Report

I reviewed with interest the article by Appiah et al. "A Prospective Population-Based Study of Cardiovascular Disease Mortality Following Treatment for Breast Cancer Among Men in the United States, 2000-2019". In this study, the authors analyzed the cardiovascular mortality in male patients with breast cancer in a population sample. This pathology is quite rare, so the registry data is interesting in itself. Undoubtedly important are the revealed facts about the increase in cardiovascular mortality during chemotherapy and the absence of influence on it during radiation therapy, as well as ethnic differences in cardiovascular mortality.

However, when reviewing the manuscript, I had questions and comments to which I would like to receive answers from the authors.

1.       The data presentation format looks bad. Since the main thing in the article is the analysis of cardiovascular mortality, it would be most adequate to present the results in the groups of patients without cardiovascular death / patients with cardiovascular death. Alternatively, as an option - surviving patients / deceased from cardiovascular death / deceased from other causes. Then the data would be more complete and understandable. The data in Table 1 does not provide information on this issue at all.

2.       The article does not contain data on the absolute number of deaths from both all causes and cardiovascular in the studied groups (No chemotherapy, no radiotherapy / Chemotherapy, no radiotherapy / No chemotherapy, radiotherapy / Chemotherapy and radiotherapy). I consider it obligatory to provide data not only on cardiovascular mortality, but also on general mortality. Since otherwise the reader of the article may have the following question - perhaps radiation therapy does not affect cardiovascular mortality, but is less effective in preventing death from other causes?

3.       This article lacks many indicators that could better characterize the studied cohort of patients (risk factors, comorbid cardiovascular diseases, chemotherapy regimens, whether or not receiving hormone therapy, HER2 positivity status). The authors refer to the absence of such data in the SEER register. At the same time, these data are available in the large National Cancer Database (NCDB), the data of which was used in writing a recent article (1). Maybe it was necessary to continue using this more complete database and analyze cardiovascular mortality in this category of patients using it.

4.       At the end of the Discussion section, among the limitations of the study, the authors write "Finally, the chance of misclassification bias influencing the results of the study due to the use of death certificates to identify deaths attributable to CVD cannot be entirely ruled out. However, cause-of- death information in the SEER registry have been reported to have good validity". However, the link provided by the authors validates data not from the SEER registry, but from another one (California Cancer Registry). I think a more correct link is needed.

 

Minor

1.       1. In tables 1 and 2, in figure 1, the meanings of abbreviations (ER, PR, etc.) are not shown.

2.       The ordinal numbers of sources in the list of references are given twice.

3.       Figure 1 lacks statistical difference values.

 

Reference:

1.     Yadav S, Karam D, Bin Riaz I, Xie H, Durani U, Duma N, Giridhar KV, Hieken TJ, Boughey JC, Mutter RW, Hawse JR, Jimenez RE, Couch FJ, Leon-Ferre RA, Ruddy KJ. Male breast cancer in the United States: Treatment patterns and prognostic factors in the 21st century. Cancer. 2020 Jan 1;126(1):26-36. doi: 10.1002/cncr.32472.

Author Response

Please see attached

Author Response File: Author Response.pdf

Reviewer 2 Report

I congratulate the authors to this very interesting and well written manuscript.

Author Response

Response

We thank the reviewer for the kind words and the thorough review of our manuscript

Reviewer 3 Report

This is a well written paper examining data from the SEER data set. The data limitations are known and described. They highlight the increased risk of cardiovascular mortality in male breast cancer but are unable to determine effects of other risk factors that are aligned to breast cancer risk. The same can be said for the racial variations. Further work is needed with data from other sources to understand this better and help design treatment pathways for men with breast cancer balancing the risk against cardiovascular health.

On a positive note, it is reassuring to see further data showing a reduction in the cardiovascular risk from breast radiation which reassures that evidence of risk does lead to practice change to reduce risk.

Author Response

Response

We thank the reviewer for the kind words and the thorough review of our manuscript

Round 2

Reviewer 1 Report

I am grateful to the authors for the work done to correct the manuscript, I was satisfied with the answers to my questions and comments. I have no other comments.