Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review

Round 1

Reviewer 1 Report

This is a very well-written and thorough investigation of the literature on breast metastasis from primary lung carcinoma.  I think the authors nicely summarized the existing literature, including the case reports, and provided guidelines on how to treat these complex cases.  My only suggestion would be to provide more rationale for the surgical management of the breast disease (i.e., why a sentinel node biopsy was performed).

Author Response

Reviewer 1

This is a very well-written and thorough investigation of the literature on breast metastasis from primary lung carcinoma.  I think the authors nicely summarized the existing literature, including the case reports, and provided guidelines on how to treat these complex cases. 

Thank you so much

Point 1

My only suggestion would be to provide more rationale for the surgical management of the breast disease (i.e., why a sentinel node biopsy was performed).

Response 1

Thank you. Done.

Sentinel lymph node biopsy represents the gold standard for early breast cancer surgery and was necessary because of the uncertainty about the origin of the disease (primary breast cancer versus metastasis from lung cancer). This intervention made it possible to obtain much histological material to perform all the to molecular and immunohistochemical analyzes necessary to define the origin of the tumor. (Lines 80-85)

 (with sentinel lymph node biopsy if a breast cancer is suspected) pag.7

Author Response File: Author Response.docx

Reviewer 2 Report

Thank you for the opportunity to review your manuscript titled Complex differential diagnosis between primary breast cancer and breast metastasis from EGFR mutated lung adenocarcinoma: case report and literature review. It's an interesting review with case report. I have a few comments to the authors:

Abstract: The authors only talk about the clinical case. It would be interesting to introduce aspects of the literature review.

Keywords: Please, use MeSH terms. For example, Lung neoplasms.

2. Case report: Provide more information about the case: weight, height, BMI, if the patient takes any medication ...

3. Literature review: results and discussion: In a literature review, the results are as important as the methodology to reach them. Although it is schematic, it is necessary to indicate the databases consulted, dates, words used in the search, inclusion criteria, and the filtering of all articles initially found and their process until reaching the number of final articles.

Does your study have any limitations?

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 3 Report

Although rare, breast metastases of lung adenocarcinoma have already been extensively analyzed from both a histopathological and a molecular point of view, with particular regard to thyroid transcription factor-1, as well as to the receptors for EGF, estrogens or progesterone (see, for example: Liam CK, Respirol Case Rep 2013; Mirrielees JA, J Surg Res 2014; Lin Q, BMC Cancer. 2016; Assouline P, Rev Mal Respir 2017; Wan X, Int J Gen Med 2020). Therefore, this manuscript does not present characteristics of originality: for this reason, it could be considered for publication only as a confirmatory study of data already shown by other research groups. In this sense, therefore, the paper should be reformulated if the Journal decides to publish it. Finally, it has to be emphasized that some of the papers cited above have evaluated more than one single case.  

Author Response

Please see the attachment

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Thank you for the opportunity to review the revised manuscript. With the changes made by the authors, the version of the manuscript has been improved. Good job!

Reviewer 3 Report

Dear Author, I sincerely believe that the work you submitted is essentially similar to the combination of the ones I have mentioned. In fact, while Liam 2013, Lin 2016 and Assouline 2017 reported newly diagnosized cases of primary lung carcinoma which metastasized to the breast, Mirrielees 2014 and Wan 2020 reviewed analogous, but previously published case reports in order to assess common clinical and pathologic features and management strategies. All these papers concluded that in patients with lung adenocarcinoma and EGFR mutation, immunohistochemical and molecular examinations (evaluation of TTF1 expression included) are needed to confirm the nature of the synchronous breast tumour, and to guide patients' treatment. This being so, your manuscript does not appear original. I do not mean that your study is uninteresting, but only that it confirms results previously published by other Authors. I therefore believe that publishing it or not can only be a choice of the Editors of Current Oncology.