Autoantibody Diversity Is Augmented in Women with Breast Cancer and Is Related to the Stage of the Disease

Round 1

Reviewer 1 Report

General comments

- In order to demonstrate the significance of autoantibodies in breast cancer, the article "Autoantibodies Diversity is Augmented in Women with Breast Cancer and Is Related to the Stage of the Disease" is quite intriguing. 

- The introduction, methodology, and discussion sections are all clearly presented, with the exception of the results section, which still needs improvement.

specific comments

- Suggest to put a statistical value on figure 4 A and B

- Even though procedures are described in the method section, there is no western blot result in the result section

-Additionally, despite being mentioned in the methods section, there is no imaging analysis result in the results section.

Author Response

Specific comments

- Suggest to put a statistical value on figure 4 A and B

Thank you for your effort and valuable commentaries. With regard to the suggestion to add statistical value to Figure 4A and B, we have included the analysis of the Shannon entropy (H index) for which Hutcheson's t-test for two diversity indices was used (which requires H values only). We included in Supplementary Material Figure S2, which reflects the analysis of the H index. The Effective Number of Species depicted in Figure 4 was calculated from the H index (ENS= e^H), and they follow the same behavior in the different groups. 

- Even though procedures are described in the method section, there is no western blot result in the result section.

The Western Blots were added to the manuscript in supplementary material (Figure S1).

-Additionally, despite being mentioned in the methods section, there is no imaging analysis result in the results section.

The database, which includes the bands detected in each serum, was added to the manuscript as supplementary material (Table S1)

Reviewer 2 Report

MS: Autoantibodies diversity is augmented in women with breast cancer and is related to the stage of the disease

The above MS presents an analysis of the diversity of autoantibodies reactive to antigens expressed by the BC (cell line T47D) in sera of Mexican women with BC, benign breast pathology (BBP), or without breast pathology (WBP). This study reveals that this diversity was higher in the BC and BBP groups compared to the WBP group. Also, the study results have demonstrated that the diversity changed with the progression of BC (e.g., it declined in the advanced stages of BC). These findings may suggest that the measurement of the autoantibody response may be helpful as a potential tool for BC screening and prognosis. However, further prospective large-scale research studies are needed in this area.

Comments to Authors have been provided below.

In the Discussion, the Strengths and Limitations of the study should be clearly stated (vs. only a brief sentence mentioned in the Conclusions).

Also, the Future directions section should be added to the Discussion. In this section, the Authors may mention that disseminating knowledge, among clinician’s and researcher’s teams, about measuring autoantibodies can facilitate a more precise diagnosis of BC [e.g., subtype or stage], predict response to some treatment options [e.g., CHT, RT, hormonal therapy, or target therapy], and allow to make more precise therapeutic decisions. The Authors may comment on the use of immunotherapy [e.g., immune checkpoint inhibitors (ICI) like PD-L1 and PD-1 inhibitors] in women with BC [e.g., the autoantibody levels in the serum of patients with BC may be useful for monitoring treatment effects during ICI therapy].

A list of abbreviations needs to be added at the end. The abbreviations should be explained in the legend of tab.1 [e.g., SBR, ER, PR] and in fig.1-4 [e.g., BBP, WBP].

Author Response

-In the Discussion, the Strengths and Limitations of the study should be clearly stated (vs. only a brief sentence mentioned in the Conclusions).

Also, the Future directions section should be added to the Discussion. In this section, the Authors may mention that disseminating knowledge, among clinician’s and researcher’s teams, about measuring autoantibodies can facilitate a more precise diagnosis of BC [e.g., subtype or stage], predict response to some treatment options [e.g., CHT, RT, hormonal therapy, or target therapy], and allow to make more precise therapeutic decisions. The Authors may comment on the use of immunotherapy [e.g., immune checkpoint inhibitors (ICI) like PD-L1 and PD-1 inhibitors] in women with BC [e.g., the autoantibody levels in the serum of patients with BC may be useful for monitoring treatment effects during ICI therapy].

 

In attention to your valuable comments, we added at the end of the Discussion section the following paragraph:

Finally, in this article, we present for the first time a study on the diversity and abundance of autoantibodies for breast cancer in the Mexican population. Although the sample is small for each group, the inclusion of patients previous to the initiation of cancer treatment and the selection criteria allowed us to compare patients in similar conditions. Likewise, we used community ecology tools to compare the different groups; to our knowledge, this is the first time such tools have been applied to the analysis of the diversity of antibodies in breast cancer research. This type of research has the potential to provide more information about the different possible scenarios in breast cancer, from subtypes of breast cancer to the monitoring of the progression and response to treatments. In this sense, our study provides a research strategy to be applied in the above-mentioned scenarios of breast cancer as well as in other types of cancer or even in autoimmune diseases. Despite the above, this type of work still needs to be more widely disseminated among the clinical community, in order to 1) favor research with a diversity of samples (biopsies and serum) and patients with different stages and treatments, 2) propose the use of autoantibodies as diagnostic tools, in addition to the immunohistochemical analyses that are already performed to identify the tumor's hormonal susceptibility.

 

-A list of abbreviations needs to be added at the end. The abbreviations should be explained in the legend of tab.1 [e.g., SBR, ER, PR] and in fig.1-4 [e.g., BBP, WBP].

Your petition has been attended.

Round 2

Reviewer 1 Report

The authors incorporate the suggestions