A Population Description of Young Women with Breast Cancer in Newfoundland and Labrador

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

I reviewed this paper on it's initial submission. It is clear the authors have put a great deal of work into improving the paper and have responded to all the comments made by the 3 reviewers satisfactorily. I therefore think it can now be published. 

Author Response

Thank you kindly for your comments.

Author Response File: Author Response.pdf

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

General comments
The spelling and punctuation are very good. No issues were detected.
Abstract
The abstract is concise. All the necessary information about the study is included.

Background
- The information provided in the introduction is important for the comprehension of the article.
- The objective of the study is clearly mentioned.
Methods
- The methods are sufficiently explained by the authors.

Results
- The results are presented in a very extensive way.
- The figures and tables are really helpful and necessary for the completion of the authors' work.
Discussion
- The discussion is of great quality and includes updated data.
- The authors inform the reader about the study's limitations.
Conclusion
From the presented data, the conclusion is complete and represents the work that the authors did.

Revision

1) The majority of information included in Table 1 is also in table 2. You can gather all the information in one table.

2) Despite the major advances in breast cancer surgery, there are still numerous unanswered questions regarding the histological subtype of Invasive micropapillary carcinoma.

I would like a brief discussion on Invasive micropapillary carcinoma of the breast. Please consider citing the recently published articles:

https://pubmed.ncbi.nlm.nih.gov/35310681/

2) "HER2 is an established prognostic and predictive marker for patients with invasive breast cancer. The clinical and biological significance of HER2 overexpression in patients with ductal carcinoma in situ (DCIS) remains poorly defined. DCIS is a heterogeneous disease and some patients with DCIS will not progress to invasive breast cancer."

Add this important information and make a brief discussion on the clinical significance of HER2 expression in DCIS.

Consider citing recently published articles on this topic:

https://pubmed.ncbi.nlm.nih.gov/36352293/

Author Response

1) The majority of information included in Table 1 is also in table 2. You can gather all the information in one table.

Author's response: Thank you for this suggestion, we have combined the data into one table (table 1) as recommended. 

2) Despite the major advances in breast cancer surgery, there are still numerous unanswered questions regarding the histological subtype of Invasive micropapillary carcinoma.

I would like a brief discussion on Invasive micropapillary carcinoma of the breast. Please consider citing the recently published articles:

https://pubmed.ncbi.nlm.nih.gov/35310681/

Author's response: Thank you kindly for this suggestion, the attached article was reviewed as  recommended. We did not feel however that discussing invasive micropapillary carcinoma was pertinent to our topic, as we do not discuss any specific histologies in great detail or how they pertain to young women with breast cancer. 

2) "HER2 is an established prognostic and predictive marker for patients with invasive breast cancer. The clinical and biological significance of HER2 overexpression in patients with ductal carcinoma in situ (DCIS) remains poorly defined. DCIS is a heterogeneous disease and some patients with DCIS will not progress to invasive breast cancer."

Add this important information and make a brief discussion on the clinical significance of HER2 expression in DCIS.

Consider citing recently published articles on this topic:

Author's response: Thank you kindly for this suggestion, the attached article was reviewed as  recommended. We did not feel however that this was relevant to our patient population however as diagnosis of DCIS was excluded from our cohort

Author Response File: Author Response.pdf

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is an interesting paper which is well written, however, there are a few points I think should be addressed prior to publication in the methods and results.

Methods
- Please explain why age under 40 was used? Why was age <49 (before screening) not used for example.
- Why was the period 2008 - 2018 used? Why 10 years duration?
- Mention and reference of guidelines used for treatment in this region
- Mention and reference of usual follow-up protocol

Results
- I feel that the paper would have more merit if simple statistically analysis was carried out for each of the mentioned variables (Table 1), in relation to survival. For example BMI is presented and even hypothesised that this may be related to more aggressive tumour type - this could be confirmed by statistical analysis
- There is no mention of adjuvant therapies. This must be included.
- Can details on genetic mutations be included? I appreciate in the discussion is it stated that there is a lack of genetic mutation status available - why is this the case? Presumably those undergoing contralateral mastectomy had a genetic mutation or were there other reasons why? 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Overall, a topic that would likely be of interest to readers. Given that it’s a descriptive manuscript on a small population, more details are needed about the cohort studied. Very basic data is presented. 

 

Methods could be more robust by describing how ER/PR/Her were extracted? From path reports or clinical notes? If path reports, were ASCO guidelines utilized?

 

Lines 128-131 – comment on what stages were treated with neoadjuvant. Were stage 2 TNBC or HER2 positive offered neoadjuvant? 45 pts were HER2 positive, 41 were TNBC, but only 32 received neoadjuvant – can this be explained further? Due to timeframe and changing practices, so more of these patients were diagnosed before neoadjuvant became standard of care?

 

62 patients were HR+, but 81 received ovarian function suppression – commenting on this and explain this further

 

Include information about geography of province and where care is delivered. Did all these individuals come through one centre? Was their location (i.e. postal code, distance from cancer centre) evaluated to see if this impacted treatments offered and survival?

 

Inclusion of regimens used, and duration of endocrine therapy would also allow for better understanding of the clinical practice in the province – please include. What regimens were used, were there issues with access to certain systemic therapy?

 

Given this is a descriptive study, more explanations of the practices and trends seen are required in the discussion. You touch upon this in line 224, but more details in the results would allow readers to understand the clinical treatment landscape of the province.

 

Paragraph starting at line 199, note lower survivals – further description of the treatments used would provide more information on factors that are impacting this

 

Line 234 – discuss importance of adhering to guidelines. Reviewing the local and systemic treatment given in detail and how this aligns with the guidelines during the timeframe evaluated would be useful

 

Given the recognized importance of fertility, mental health and psychosocial support in AYA – including theses as secondary outcomes, or discussed as a limitation of this paper since it wasn’t assessed

Comments on the Quality of English Language

No major concerns noted.  Some minor typos – requires proofing – ie. Page 1, line 31, include ‘years’ after 15-39

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

In this manuscript Mohoney et al. presented a retrospective analysis on a cohort of young (< 40 years of age) breast cancer patients and reported their pathologies, overall survival rate and disease-free survival rate in province of Newfoundland and Labrador. The cohort is relatively smaller compared to previously published similar analysis in different demographics. However, this analysis provides a locoregional insights in the breast cancers incidence among young women of Newfoundland and Labrador. Overall Introduction, methos, Results and Discussions were clearly presented.

However, the Figures/survival data should be presented in Kaplan-Meier estimator graphs.

In some instances, data interpretation and discussion should be revised. For example, Line 164: Since the cohort sizes are different between different studies, Chi-square test should be performed between cohorts in order to draw conclusion whether the rate is higher. Same is true for other variables such as obesity, BMI etc. Authors should perform statistical analysis between the groups to make any quantitative statements in relation to published studies.

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf