Diagnostic and Therapeutic Challenges in a Patient with Ureteral Metastases from a Triple Negative Breast Cancer

Round 1

Reviewer 1 Report

Breast Cancer is the most common cause of cancer and with the highest mortality rate, the most common sites of metastasis are bone, lungs, liver, and pleura, metastasis to the ureter is rare. The same case report has been reported earlier and around 19.5% patients of with breast cancer have been diagnosed with ureteral metastases. Although ureteral metastases from breast cancer are uncommon, the reports in the literature show an increase in such spread over the years.

 The case report by Saranti et al. is unique and challenging considering the fact that the patient was an 87-year-old woman with several other comorbid conditions including diabetes Mellitus. The report is represented precisely with details of the 8F-FDG PET/CT scan. It will be interesting to evaluate the functional role of SOX10, and GATA3 as an important regulators of T cells. As the author mentioned in the report that “Imaging modalities such as CT, MRI and PET/CT are necessary for diagnostic, but they are not specific for metastatic ureteral tumors.

 

With reference to the current case report author recommended the useful impact of  (18)F-FDG PET/CT which can be useful to assess the metabolic activity through close correlation with CT images. 

Author Response

Thank you very much for your time to review our case report.

1. Epidemiology of this rare condition. Thank you very much for providing additional data.
2. Evaluate the functional role of SOX10, and GATA3 as an important regulators of T cells. We think that this information is beyond the scope of our case report.
3. Regarding the impact of  (18)F-FDG PET/CT in the diagnosis, even though not pathognomonic, is important as an additional tool. 

Reviewer 2 Report

This is a very case of ureteric breast secondaries in an older woman. The author describes the patient's presentation and course well. 

Whilst the patient had a good outcome in the end, more details are needed regarding her oncological background. More information about the previous lymphoma and breast cancer is needed; what histological subtype of lymphoma and its primary site and how it was treated are very relevant, both to her subsequent breast primary and secondary.

The author mentioned that the breast primary was treated by partial mastectomy, however, no details were provided regarding nodal management and status. A sentinel node biopsy or axillary clearance is the standard practice for the management of any breast primary. The author mentioned that the stage was pT2Nx which indicates the nodal status is unknown, why is that? Another standard practice which would be of great importance in triple-negative breast cancer is adjuvant or neoadjuvant treatment. The standard practice for these patients is at least to get adjuvant radiotherapy following a partial mastectomy which will have a great impact on prognosis. 

The author mentioned in line 53 that serum tumour markers were normal. What markers specifically and for which tumour?

Was there a ureteric stent put in for this patient during her course of treatment?

The patient presented with a bleeding peptic ulcer, and while she was in hospital started having painless hematuria. How was the peptic ulcer managed? Triple-negative breast cancer is known to be related to gastric cancer, as both can metastasize to either site. Was that possibility investigated? Was the ulcer biopised?

Author Response

Thank you very much for reviewing our case report.

1. As you can see in the re-submitted manuscript we have tried to improve the description of the methods and the presentation of the results.
2. We have added more details regarding the previous lymphoma and breast cancer treatment.
3. Breast cancer: lymph node biopsy, radiotherapy, systemic treatment. The patient did not have a sentinel node biopsy because of her age and the absence of enlarged lymhnodes in the CT thorax. Information on adjuvant treatment provided.
4. Tumor markers. Added.
5. Ureteral stent. Was inserted.
6. Peptic ulcer - Triple negative breast and gastric cancer.: Gastroscopy reveald diaphragmatic hernia. Managed conservatively.

Reviewer 3 Report

I have read this article with a lot of interest as breast cancer is a fundamental part of my practice.

The authors propose a case report of a woman with metastatic TNB breast disease after 7 years.

The card has point mounts that need to be improved and make the card interesting for readers

1) In the clinical case part I suggest implementing the discussion on follicular lymphoma treatment, did the woman have radiotherapy to treat it? Dove? At what dose?

2) Broader Discussion of Breast Cancer, Did the Woman Perform Mastectomy Only? underarm treatment? Triple negative breast cancer poses a major treatment challenge, clarifying adjuvant chemotherapy treatment.

3) Has the woman been subjected to a genetic study for mutations related to the neoplasms she was affected by?

4) Please fix the figure 2a and standardize all the figures, improve the quality.

 

 

 

 

Author Response

Thank you very much for reviewing our case report.

1. We have tried to improve the research design, although taking into account that this is a case report aiming at presentig the real facts.
2. Does the introduction provide sufficient background and include all relevant references? Are the methods adequately described? Are the results clearly presented? Are the conclusions supported by the results?Are all the cited references relevant to the research? All these points must be improved. Please see revised manuscript.
3. Discussion on follicular lymphoma treatment, did the woman have radiotherapy to treat it? Dove? At what dose? Please see manuscript.
4. Triple negative breast and gastric cancer. Please see manuscript.
5. Did the Woman Perform Mastectomy Only? underarm treatment? Triple negative breast cancer poses a major treatment challenge, clarifying adjuvant chemotherapy treatment. No sentinel biopsy was performed due to her age and negative imaging of axilla.
6. Has the woman been subjected to a genetic study for mutations related to the neoplasms she was affected by? No, due her age.
7.  Fix the figure 2a and standardize all the figures, improve the quality. Please see manuscript.

Round 2

Reviewer 2 Report

Thanks for reviewing. A diaphragmatic or Hiatus Hernia on its own would not cause upper GI bleeding, unless it's complicated by ulceration or oesphagitis. May the authors please clarify the cause of bleeding or whether any was found?

You mention in line 48 that the patient had a sentinel node biopsy which would be standard practice in these cases. However, you then say the tumour stage is pT2Nx. The Nodal stage should not be Nx given that you did a node biopsy procedure. Please revise and amend or explain.

Tumour markers that are relevant to Breast Cancer are CA15-3, and CA27.29. The rest of the markers listed are not really relevant to either Lymphoma or Breast Ca. 

Author Response

Thanks for reviewing. A diaphragmatic or Hiatus Hernia on its own would not cause upper GI bleeding, unless it's complicated by ulceration or oesphagitis. May the authors please clarify the cause of bleeding or whether any was found?

The bleeding was attributed to oesophagitis due to diaphragmatic hiatus hernia.

You mention in line 48 that the patient had a sentinel node biopsy which would be standard practice in these cases. However, you then say the tumour stage is pT2Nx. The Nodal stage should not be Nx given that you did a node biopsy procedure. Please revise and amend or explain.

I do apologize for the wrong information provided. The patient did not had a sentinel node biopsy, a decision based not on guidelines but on the judgment of the surgeon and on the age of the patient.

Tumour markers that are relevant to Breast Cancer are CA15-3, and CA27.29. The rest of the markers listed are not really relevant to either Lymphoma or Breast Ca.

I agree with your comment and suggestion. Unfortunately, the patient underwent this extra examination, in order to guide the physicians to a closer diagnosis (“Fishing” procedure).

Reviewer 3 Report

I am pleased to see that the authors have modified the work according to the indications given by me. However, clarifications are still needed:

- The authors have clarified the chemotherapy treatment of the lymphoma (therapeutic scheme and timing), therefore no radiotherapy treatment was carried out?

- I thank the authors for having better specified the type of surgery and for having given more information on the chemotherapy treatment. However, it is not clear in the text whether or not the sentinel lymph node was removed: "A partial mastectomy with sentinel lymph node biopsy was performed", but the authors' answer to the question in the report is "No sentinel biopsy was performed due to her age and negative imaging of axilla ". If the sentinel lymph node was not performed, it would be correct to report it in the text, clarifying the reasons; if the sentinel lymph node has been removed, why is it "Nx" on histological staging?

- Figure 2.a has not been arranged as required, it would be advisable to straighten it. Also I don't notice an improvement in the quality of the images.

Author Response

I am pleased to see that the authors have modified the work according to the indications given by me. However, clarifications are still needed:

- The authors have clarified the chemotherapy treatment of the lymphoma (therapeutic scheme and timing), therefore no radiotherapy treatment was carried out?

No radiotherapy was administered for the treatment of lymphoma.

- I thank the authors for having better specified the type of surgery and for having given more information on the chemotherapy treatment. However, it is not clear in the text whether or not the sentinel lymph node was removed: "A partial mastectomy with sentinel lymph node biopsy was performed", but the authors' answer to the question in the report is "No sentinel biopsy was performed due to her age and negative imaging of axilla ". If the sentinel lymph node was not performed, it would be correct to report it in the text, clarifying the reasons; if the sentinel lymph node has been removed, why is it "Nx" on histological staging?

We do apologize for the confusion caused due to this totally misleading information. We repeat that “No sentinel biopsy was performed due to her age and negative imaging of axilla".

- Figure 2.a has not been arranged as required, it would be advisable to straighten it. Also I don't notice an improvement in the quality of the images. Previous comment “Please fix the figure 2a and standardize all the figures, improve the quality.”

{Instructions: File for Figures and Schemes must be provided during submission in a single zip archive and at a sufficiently high resolution (minimum 1000 pixels width/height, or a resolution of 300 dpi or higher). Common formats are accepted; however, TIFF, JPEG, EPS and PDF are preferred.}

I have looked at your previous comments on the quality of the figures and I must admit that I do not understand what you mean by “fix the figure 2a”. The resolution of the imaging figures is in accordance with the Journal’s instructions (300 dpi).

Round 3

Reviewer 3 Report

Thanks for making the suggested revisions. Of what previously reported, only figure 2a remains to be corrected: the picture seems to be slightly out of assis, the border of the image do not align with the picture itself making it look a bit crooked. 

Author Response

I hope that this figure is in accordance with your comments.

Dimitrios Kardamakis

Author Response File: Author Response.docx