Effect on Germline Mutation Rate in a High-Risk Chinese Breast Cancer Cohort after Compliance with The National Comprehensive Cancer Network (NCCN) 2023 v.1 Testing Criteria

Round 1

Reviewer 1 Report

The data could be clinically relevant but paper is difficult to read.  The writing style is challenging: sentences are dense and not well-written,  and the grammar/choice of words require revisions to make the paper flow and be clear.  I advise that the paper be modified to make the NCCN guidelines on which the paper is based be much more clearly defined early in the paper, that the overall presentation be simplified and clarified so the reader can clearly understand the underlying genetic and clinical aspects, and I do advise that a native English speaker review the grammar and choice of wording.  You have clearly collected a lot of data and done a lot of work on this paper-but I advise it be presented in a more clear form that points out the relevance of your research to the reader.

Author Response

The data could be clinically relevant but paper is difficult to read.  The writing style is challenging: sentences are dense and not well-written, and the grammar/choice of words require revisions to make the paper flow and be clear.  I advise that the paper be modified to make the NCCN guidelines on which the paper is based be much more clearly defined early in the paper, that the overall presentation be simplified and clarified so the reader can clearly understand the underlying genetic and clinical aspects, and I do advise that a native English speaker review the grammar and choice of wording.  You have clearly collected a lot of data and done a lot of work on this paper-but I advise it be presented in a more clear form that points out the relevance of your research to the reader.

Figure 1 was added to the manuscript for better presentation. A native English speaking person was also invited to advice on the wording and presentation.

Reviewer 2 Report

1. The authors are advised to provide the intricate molecular mechanisms behind their observations.

2. It will be also highly appreciable if the authors can provide some relevant in vivo studies in support of their observations.

Author Response

Both questions can be answered together. The relevant literature and discussion can be found from line 208-240. We are certainly interested in the molecular mechanism and in vivo studies (presumably animal model or cellular models). We are a clinical service department and clinical service laboratory, our expertise is in patient management and we deliver clinical tests. We focus on collecting clinical data to analysis with our limited resources. We wish this observational data can inspire the talented to develop mechanistic or molecular models.

Reviewer 3 Report

Comments and Suggestions for Authors：

Title: Effect on germline mutation rate in a high-risk Chinese breast cancer cohort after compliance with The National Comprehensive Cancer Network (NCCN) 2023 v.1 testing criteria

From 2007 to 2022, the author collected 3797 samples of high-risk breast cancer patients. Firstly, grouped the above patients according to the NCCN testing criteria (2023 v.1 and 2022 v.2). Then through DNA sequencing, BRCA1/2 and 6 high-penetrance genes mutation rates in these samples were detected. Finally, based on these results, the author indicated that these studies would increase the positive detection rate, and potentially more patients would benefit. It is an important study, but there are some problems, which must be solved before it is considered for publication.

1-      The current manuscript lacks the supplementary Table 1.

2-      The results were not clearly presented. Adding some statistical images may make it easier to present the results.

3-      Authors need to check the spellings in current manuscript, such as line 117 on page 3.

Author Response

1-      The current manuscript lacks the supplementary Table 1.

Supplementary Table 1 is attached

2-      The results were not clearly presented. Adding some statistical images may make it easier to present the results.

            Figure 1 is added to the manuscript.

3-      Authors need to check the spellings in current manuscript, such as line 117 on page 3.

            Changed accordingly

Round 2

Reviewer 1 Report

Thank you for amending the paper.