Review Reports - Mesenchymal Tumors of the Breast: Fibroblastic/Myofibroblastic Lesions and Other Lesions

Round 1

Reviewer 1 Report

The article entitled “Mesenchymal Tumors of the Breast” has been evaluated. Personally, I am not against a long review in the Journal. However, it must be exciting and able to attract the general audience of the journal to finish the reading or at least go through the figures with a certain level of learning. I strongly recommend authors to include schematic figures of mesenchymal tumors of the breast. This would not only help the authors but also influence and impact the journal as a whole. Therefore, it is imperative for the authors to drastically improve the presentation of the figures with the goal of interesting the general audience of this journal in mind, not just a few experts in this area.

Author Response

Hi Current Oncology Reviewer,

Thank you for the edits. I have added pathology slides and summary tables to help readers be more engaged.

Riordan Azam

Reviewer 2 Report

In this article, the authors have compiled various types of mesenchymal breast tumours as fibroblastic or myofibroblastic lesions along with the lesion of smooth muscle, neural tissue, adipose tissue, vascular tissue etc based on their site of origin. The work is fascinating as it is the first time that these data are assembled together in a review article. However, some minor modifications must be done before it can be accepted.

1. Recent statistics on breast cancer can be added in the introduction.

2. Elaborate on the objective and novelty of this work.

3. Add a summary of the work at the end along with concluding remarks.

4. Add a graphical abstract to this review article.

5. Grammatical errors and spelling mistakes need to be corrected.

Author Response

Hi Current Oncology Reviewer,

Recent statistics on breast cancer - do you mean on epithelial breast cancer?
Elaborate on the objective and novelty of this work. - I elaborated on this and created a new section to explain!
Add a summary of the work at the end along with concluding remarks. - I added a summary as well as summary tables.
Add a graphical abstract to this review article. - does this happen now or separately afterwards?
Grammatical errors and spelling mistakes need to be corrected. - I have made some corrections on the most recent version.

Thank you for the corrections!

Rio

Reviewer 3 Report

The authors should be commended for a review of this topic that does frequently require multidisciplinary management, especially with the lack of data and representation in recent trials. A few comments / questions below

1. (Line 27) Please explain how the "growing use of molecular testing" is making the management more complicated. Do the authors mean the uncertainty about validity of molecular testing (such as oncotype , mammaprint ...) in these tumors?

2. (Line 47) occuring "in"

3. (Line 61-62, 80-81): It is a bit unclear if the recommendation is for excisional biopsy or just core needle biopsy. Given the rarity of these tumors, and not each facility having specialized pathology, do the authors recommend one approach over another, especially to avoid missing a more aggressive lesion?

4. Is there a need for margin assessment for NF?

5. (Line 154) account "for"

6. (Line 176-178) Are PET scans used for management of breast desmoid tumors?

7. (Line 362-369) The flow of this paragraph is a bit confusing, would appreciate if the authors review. I believe the message is that spread is hematogenous so no need for axillary staging, and cases that metastasize are enriched for FS-DFSP. Please clarify

8. Authors should be commended for noting when genetic testing / predisposition syndromes could be associated with certain tumors

9. There may not be data about this, but are the authors aware whether any of these mesenchymal tumors are actually associated with an increased risk of breast carcinomas?

10. (Line 678-683): it does seem like excision may be the safer approach to angiolipomas to avoid missing an underlying more aggressive neoplasm. If yes, may be worth being clearer here in that recommendation

Author Response

Dear Current Oncology Reviewer,

Thank you for taking the time to review this paper!

Thank you for pointing this out, I meant that molecular testing has helped with the diagnosis rather than complicated it - I have changed my wording to reflect that
Thank you - corrected this mistake
Corrected the wording here - we are recommending excisional biopsies despite some reports suggesting CNBs may be sufficient.
We couldn't find any data on margin assessments in NF - I changed the sentence there to reflect this more clearly.
Corrected
The desmoid tumor working group doesn't recommend PET - I added a sentence to reflect this.
Reviewed and changed, that is what I was trying to say but I agree it was worded wrong.
Thank you!!
I will add this to another section/paragraph about differentiating mesenchymal tumors from breast cancer that another reviewer requested!
Reviewed this paragraph as well and clarified our recommendation - the two sentences seemed to contradict each other. I meant to clarify that the excision is recommended for cellular subtypes of angiolipomas

Thank you again for being so clear in your recommendations and questions!

Riordan Azam

Reviewer 4 Report

This is a well organized review article focusing on those uncommon breast mesenchymal tumors originating from non-epithelial cells, such as fibroblastic cells, smooth muscle, neural tissue, adipose tissue, et al. It may meet the interests of researchers or benefit physicians in the filed of breast cancer. In addition to the detailed description and discussion of those rare cases, I suggest the authors to prepare a Table to conclude diagnostic indicators distinguishing those mesenchymal tumors from epithelium-origin cancers, as well as the applicable therapeutic strategies.

In the section of Introduction, some sentences unrelated with the current article should be removed, such as “This review has two parts; (1) fibroblastic/myofibro- 35 blastic and other lesions and (2) fibroepithelial lesions. Herein we present the first paper......”. In addition, comparisons between breast mesenchymal tumors and general breast cancer tumors should be included for the distinguishment.

Author Response

Dear Current Oncology Reviewer,

I have added summary tables with differentiators for fibroblastic/myofibroblastic tumors from their common differentials as you suggested.

I removed the part unrelated to this paper.

I added comparisons to epithelial breast tumors in my summary table where this was a common confounder.

Thank you,

Riordan Azam

Reviewer 5 Report

This is a very comprehensive literature review about the Mesenchymal Tumors of the Breast. The topic is relevant and well supported by the references. Only minor suggestions are included:

1.Inflammatory myofibroblastic tumor and Dermatofibrosarcoma protuberans are both intermediate tumors that belong to the borderline category. They can be classified as "ICD 2". Therefore, it may not be appropriate to classify them as purely malignant tumors.

2.Pseudo-angiomatous stromal hyperplasia is not a tumor, which differs from the auther's suggestion.

3.The manuscript stated that nodular fasciitis is a rare, benign fibroblastic lesion that occurs in 47 young patients on the upper extremities, head, neck, and rarely in the breast. However, nodular fasciitis is not rare, although it may be less common.

4.The immunophenotype for Inflammatory Myofibroblastic Tumors was incorrectly listed as CD24, whereas it should have been CD34.

Author Response

Dear Current Oncology Reviewer,

Thank you for these corrections. To your points:

Agreed, I have corrected this in the schema in the introduction
Does using words like lesion suggest it is a tumor? I didn't want to exclude the unusual mass-forming PASH situations. I changed a few of the words, but perhaps it still sounds tumor like?
Agreed again, especially compared to other tumors in this group. I changed my wording to "uncommon" instead of rare.
Yes, typo mistake. Also changed this to CD34.