Systematic Review of Nomograms Used for Predicting Pathological Complete Response in Early Breast Cancer

Round 1

Reviewer 1 Report (Previous Reviewer 1)

We appreciate the authors addressing all the comments 

Author Response

We thank you for your comments and suggestions.

Reviewer 2 Report (Previous Reviewer 2)

General comments

- The author incorporate the suggestions but still no caption on figure 1.

Author Response

We added the caption to the figure: “Study selection flowchart”.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

The authors address the issue of normogram generation for the prediction of pCR in breast cancer, which is a surrogate for survival outcomes in that disease

A few questions / comments

1. Are normograms being used in clinical practice to select patients for neoadjuvant therapy in certain clinical settings? If yes, it would be important to report on that as would bring more context into why a systematic review of normograms is important. It seems from the authors conclusions they do not feel normograms will play a role in breast cancer care moving forward, is that accurate 

2. As the authors mention, any review of predictive models (such as normograms) needs to take into account the updates in systemic therapy, especially in HER2 positive and triple negative tumors. With the rapid change in systemic therapy, previous normograms may become outdated fairly quickly

3. The results section is fairly confusing, and the discussion section presents more results in itself. Consider presenting any variables of interest in the results and not in the discussion section

- The breast cancer subtype breakdown (3.1) section can be re-written by breast cancer subtype ie HER2 positive / TNBC etc for more clarity

- Some background on why Ki67 was picked, and what is considered standard high vs low should be explained

4. There is significant variability in the studies reviewed, which will inherently limit any conclusions. Have the authors tried to look at one breast cancer subtype specifically to focus their analysis?

5. The discussion on normograms and limitations does not mention any emerging biomarkers in breast cancer, or even established markers such as ER/PR and HER2. There is correlation for example between HER2 levels and pCR and that is not mentioned

Please review the results section as the writeup is a bit confusing (See comments above)

Author Response

1. Are normograms being used in clinical practice to select patients for neoadjuvant therapy in certain clinical settings? If yes, it would be important to report on that as would bring more context into why a systematic review of normograms is important. It seems from the authors conclusions they do not feel normograms will play a role in breast cancer care moving forward, is that accurate.

Response: After reviewing and improving the text following the suggestions, we present in our paper the reasons why nomograms are not being used in clinical practice.

2. As the authors mention, any review of predictive models (such as normograms) needs to take into account the updates in systemic therapy, especially in HER2 positive and triple negative tumors. With the rapid change in systemic therapy, previous normograms may become outdated fairly quickly.

Response: After reviewing and improving the text following the suggestions, we present in our paper about how the rapid change in systemic therapy can make nomograms become outdated fairly quickly.

3. The results section is fairly confusing, and the discussion section presents more results in itself. Consider presenting any variables of interest in the results and not in the discussion section

Response: Reviewed and changed.

- The breast cancer subtype breakdown (3.1) section can be re-written by breast cancer subtype ie HER2 positive / TNBC etc for more clarity

Response: Reviewed and changed.

- Some background on why Ki67 was picked, and what is considered standard high vs low should be explained

Response: Reviewed and changed.

4. There is significant variability in the studies reviewed, which will inherently limit any conclusions. Have the authors tried to look at one breast cancer subtype specifically to focus their analysis?

Response: Reviewed and explained in our paper. Since there are low number of published works about this theme, it does not allow for a quantitative analysis.

5. The discussion on normograms and limitations does not mention any emerging biomarkers in breast cancer, or even established markers such as ER/PR and HER2. There is correlation for example between HER2 levels and pCR and that is not mentioned

Response: Reviewed and explained in our paper.

Reviewer 2 Report

General comments

It is extremely intriguing to summarize and provide succinct information regarding the role mammograms play in predicting the pathological complete response in breast cancer under the title "Systematic review of nomograms used for predicting pathological complete response in early breast cancer." Despite this effort, it is advised to revise by taking into account the suggestions that were given here in order to be published in this journal.

Specific comments

Method section

- Regarding Method Section 2.1, it would be preferable to prepare the questions in table form and include questions with potential answers that could be used to analyze various articles, as opposed to leaving them unanswered and making it challenging to draw consistent conclusions.

-Also in  method section 2.1, the author said that there are six questions "There were six research questions for this review:" but on subsection 2.4 says five questions: "Data was synthesized and analytically displayed specifically to answering the five questions stated for the review". Need to be consistent.

- The article's results section is poor. The result section should be rewriteable with the inclusion of a number of crucial figures and tables right after their first citation. This draws readers to the paper and makes it simple to comprehend the wider findings.

The result section

- "A total of 1120 studies were identified, of which 1097 titles and abstracts were screened considered not compatible with our pre-established inclusion criteria". This sentence is not clear for readers and suggest rephrasing. This problem is throughout the text and suggest revising all.

-  Figure 1 have not caption and incomplete by itself.

- Better to revise all supplemental materials

Author Response

- Regarding Method Section 2.1, it would be preferable to prepare the questions in table form and include questions with potential answers that could be used to analyze various articles, as opposed to leaving them unanswered and making it challenging to draw consistent conclusions.

Response: Reviewed and changed in discussion.

-Also in  method section 2.1, the author said that there are six questions "There were six research questions for this review:" but on subsection 2.4 says five questions: "Data was synthesized and analytically displayed specifically to answering the five questions stated for the review". Need to be consistent.

Response: Reviewed and changed.

- The article's results section is poor. The result section should be rewriteable with the inclusion of a number of crucial figures and tables right after their first citation. This draws readers to the paper and makes it simple to comprehend the wider findings.

Response: Reviewed and changed.

- "A total of 1120 studies were identified, of which 1097 titles and abstracts were screened considered not compatible with our pre-established inclusion criteria". This sentence is not clear for readers and suggest rephrasing. This problem is throughout the text and suggest revising all.

Response: Reviewed and changed.

-  Figure 1 have not caption and incomplete by itself.

Response: Reviewed and changed.

- Better to revise all supplemental materials

Response: Reviewed and changed.