Trastuzumab-Induced Organising Pneumonia in Breast Cancer Patient

Round 1

Reviewer 1 Report

1. How long after starting treatment with trastuzumab did the patient develop symptoms of pneumonia? Did the symptoms increase with the duration of treatment?

2. The authors focus on trastuzumab, although the patient was also treated with paclitaxel, maybe the combination of drugs gives such an effect in this case?

Author Response

Thank you reviewer for your response 

1. How long after starting treatment with Trastuzumab did the patient develop symptoms of pneumonia? Did the symptoms increase with the duration of treatment?

 

ANS- The patient developed symptoms 6 weeks after starting Trastuzumab therapy, following breast-conserving surgery.

 

No the symptoms did not increase with the duration of treatment. As soon as the patient presented to us with symptoms we held the possible offending drug as we did not want the condition to deteriorate any further.

 

 

2. The authors focus on Trastuzumab, although the patient was also treated with Paclitaxel, maybe the combination of drugs gives such an effect in this case?

 

ANS- We agree with the reviewer’s point as there are documented literature which showed that combination of paclitaxel and Transtuzumab could lead to organizing pneumonia however, In our patient we concluded that most likely cause of organising pneumonia was Trastuzumab because our patient did not develop any respiratory complaints when administered with Paclitaxel alone for first four cycles and hence did not warrant withdrawal of the same. Also, his condition improved after stopping Trastuzumab alone. Hence we concluded that in our case Transtuzumab is the likely cause.

Reviewer 2 Report

Many cases of pneumonia caused by Herceptin have already been reported, therefore the novelty of this case report is considered to be problematic, and there is insufficiently clinical evidence to report the cause of pneumonia in patients with metastatic breast cancer only by Herceptin. This is because it is clear that the immune status of patients who have already metastasized throughout the body is lower than that of the healthy conditions.  

The authors attempted to present a case of pneumonia in a patient with breast cancer as a rare side effect of transtuzumab, and how to manage them. However, there are critical concerns to be published. 1. The case has already been reported, so there is a novelty issue. It is doubtful whether other significant meanings can be classified by comparison with the existing reports (European Respiratory Journal 2003 21: 552-555; SpringerPlus volume 5, Article number: 1964). 2. It is questionable why the molecular type test was performed as a follow-up after the second chemotherapy. It should be considered whether the patient has received unnecessary cytotoxic drugs at a first line. 3. It could be considered that the pneumonia was induced by nab-paclitaxel, at that time the patient has prescribed the combination of nab-paclitaxel with transtuzumab. Even many cases of pneumonia by nab-paclitaxel already had been reported. A consideration of this possibility should be included. 4. The status of the metastasis of the patients should be specified. It also could be considered that the progression of the disease in the lung caused pneumonia. A consideration of this possibility should be included.  

Rigorous English polishing will be required.

Author Response

Thank you so much for your inputs 

1. The case presented here is a rare study but not a pilot-based study report or a novel study. 3 or more similar studies have been conducted in the past with similar outcomes as already mentioned in our manuscript.

 

2. We are extremely sorry for the confusion. Actually, The molecular type test was done in the beginning itself but the report of the molecular type test took a long time to come. After the reports came the treatment was given accordingly. In the main manuscript, it was not mentioned that clearly hence we have clarified it and attached the edited manuscript for your convenience

 

3. We agree with the reviewer’s point as there are documented literature which showed that combination of paclitaxel and Transtuzumab could lead to organizing pneumonia however, In our patient we concluded that most likely cause of organising pneumonia was Trastuzumab because our patient did not develop any respiratory complaints when administered with Paclitaxel alone for first four cycles and hence did not warrant withdrawal of the same. Also, his condition improved after stopping Trastuzumab alone. Hence we concluded that in our case Transtuzumab is the likely cause.

 

4. Even though there is no histological evidence as the lung biopsy could not be performed, the possibility of metastasis can still be effectively ruled out as there was significant radiological and clinical improvement on holding the treatment with Trastuzumab. In contrast, if there was a metastatic cause there would have been a progression and no effective response to corticosteroid therapy.

Reviewer 3 Report

Here, Dixit et al. reported a rare case of organizing pneumonia associated with Transtuzumab in metastatic breast cancer, highlighting the importance of timely diagnosis due to potential adverse patient outcomes.

It is an interesting study. However, some minor corrections are required. 

1) Kindly add few more technical information in Abstract. 

2) Elaborate the introduction part.

3) Break the paragraphs in "Case study" section.

4) I could see too many highlighted text. Kindly resolve them.

5) Also, thoroughly proofread the article to address grammatical mistakes.

6) If possible, add few more references in Introduction and Discussion sections. 

7) Elaborate the figure captions by adding few more details. 

Moderate editing of English language required.

Author Response

As requested by the reviewer we have done all the necessary corrections.

Reviewer 4 Report

The authors have presented a case report regarding Transtuzumab-Induced Organising Pneumonia In Breast Cancer Patient

First, I would suggest a reorganization of the title to signify better its meaning (Eg. Transtuzumab-Induced Organising Pneumonia in patients diagnosed with breast cancer – a case report)

Secondly, my suggestions are as follows:

ABSTRACT

·        The abstract is too short and does not emphasize the particularity of your case. Please detail the particularities in the abstract more.

BACKGROUND

·        You should use a bibliographic entry for the definition of the OP (line 17)

·        Line 19 – you should use a bibliographic entry for this statement.

·        You talk about a metastatic breast cancer – please use this also in the title

·        Line 25 - Her 2 neu – please use the official form of this oncogene (HER-2/neu)

·        The objective of your case report should be the last sentence of the background part

·        You should re-organize the background part in order to set a narrative way of reading

CASE STUDY

·        You should use as title for this part Case report

·        You have a lot of extra explications regarding paraclinical test or treatments. - for example Line 35 – immunohistochemistry.

·        You should re-write the IHC part – Eg. Immunohistochemically, the tumour cells were positive for Her-2 and negative for estrogen and progesterone.

·        Because you talk about IHC, you should put 2-3 pictures of the positive and negative staining.

·        Lines 40-54 are just theoretical things about the usage of Her2 in diagnosing breast cancers. I suggest that you should put this part in the background part. Also, you do not have any references for lines 40-54.

·        My suggestion is to re-write the presentation of your case in a structured manner because it is very hard to read and follow the information. You should better structure the clinical and paraclinical tests and the way the patient was treated.

DISCUSSION

·        The discussion part is not structured and is again very hard to read. You make statements that are not followed by adequate references.

·        My recommendation is to re-write the discussion part, to use more references and to follow a structured way of writing. Please discuss your case report based on your findings.

CONCLUSION

·        The conclusion is too large, and you repeat parts from the discussion part. Please make it simple and concise. Here you can put an accent on the particularity of the case.

References

·        The references list is too short and very old.

·        Everything that you use in the text and was not discovered by you should have a reference.

·        Please re-write this part.

The quality of english should be revised by a proofreading service. In many sentences, the words do not respect the normal topic of words and some of them do not have a subject. 

Author Response

Dear reviewers 

Thank you for your response we have made the all corrections and looking forward to publish our article 

thank you 

Round 2

Reviewer 2 Report

All concerns have been well addressed.

Moderate English polishing required.

Author Response

Thank you for your comments all the correction has been done

Reviewer 4 Report

Dear authors,

The manuscript has been revised but still has some issues. 

 

Author Response

All correction has been done 

Round 3

Reviewer 4 Report

The authors have made significant improvments to their manuscript.

Minor english editing should be performed.