Key Considerations for the Treatment of Advanced Breast Cancer in Older Adults: An Expert Consensus of the Canadian Treatment Landscape

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article examines a social problem, such as the treatment of elderly people with oncological diseases. The very structure of the article is misleading - it starts as an individual case and flows into something similar to an overview on the topic, without a clear methodology, criteria for inclusion and exclusion of referenced articles, which does not lead to a unity of conclusions. The conclusions drawn in no way contribute to anything new in the field. As a complete revision of the article in view of the criteria for writing a scientific article.

Author Response

Dear Reviewer,

Thank you for taking the time to review our paper. This work has been created as an expert consensus, and is not a systematic review or meta-analysis, which is why there is no predefined methodology for selecting studies for discussion. It is not an original scientific study and so not intended to contribute new findings or data to the field. Instead, this work is meant as an overview for general oncologists and general practitioners in oncology who treat breast cancer - as a reference paper of key considerations for these practitioners while treating this growing and often challenging patient population. The case was intended to contextualize the discussion by providing a real world example often seen in clinical practice.

Sincerely,

The Authors

Reviewer 2 Report

Comments and Suggestions for Authors

This report begins and ends with a case discussion which contextualises the review article - which discusses the challenges of caring for this cohort 

The figures and tables are excellent and complement the text - the final figure/table in particular resonated

in my jurisdiction the number of patients in this cohort will double in the next 2 decades - what is the data for canada - can it be included

section 4.2 discusses cognitive capacity - could this be expanded as it a major issue in this cohort

section 7 should include a discussion on metronomic therapy (eg PMID 33248390) which we use in this cohort 

clinical trials are integrated throughout the review - could a table of ongoing research efforts in this are be included to increase awareness and participation

Author Response

Dear Reviewer,

Thank you for taking the time to review our article. Please see below for our response to each of your helpful and constructive comments.

1. This has now been included in the Background section lines 49-54. Data is very similar in the Canadian context.
2. Section 4.2 has now been expanded to include a more in depth discussion about the challenges encountered with cognitive assessment.
3. Section 7 has now been updated to include discussion about metronomic therapy, and includes discussion of this particular study, among others.
4. Thank you for this suggestion, a table detailing pertinent ongoing research efforts has now been included.

We appreciate your thoughtful comments, and hope that these corrections are to your satisfaction. We agree that these help to improve the quality of this paper.

Sincerely,

The Authors

Reviewer 3 Report

Comments and Suggestions for Authors

This is an expert consensus of the Canadian treatment landscape for older adults with advanced breast cancer. The proposed algorithm of treatment considerations for older breast cancer patients was mainly based on the level of fitness and tumor biology. The clinical significance of this topic is inevitable, but several questions from my perspective are listed as follows. If the authors could provide rational explanations for my questions, I would endorse the acceptance of this article.

1.     Please consider adding summaries of key trials and considerations for the use of chemotherapy, immunotherapy, and anti-HER2 targeted agents in older adults in tables. 

2.     In line 93, this is the general consideration for all old adult cancer patients. How about special considerations for patients with advanced breast cancer if they would like to receive breast radical or conservative surgery?

3.     Is there any special recommendation for breast cancer in elderly men and obese adults?

4.     Are there any studies or ongoing clinical trials using novel biomarkers and agents for guiding anti-cancer therapy for elder breast cancer patients?

5.     In both the discussion and conclusion sections, not enough new information has been addressed. Please consider simplifying the contents and adding future directions and ongoing research about the management of older adults with advanced breast cancer.

6.     In Table 2, why only 1L systemic therapy recommendations for all subtypes had been discussed?

Author Response

Dear Reviewer,

Thank you for taking the time to review our article. Please see below for our response to each of your helpful and constructive comments.

1. Two additional tables have now been created and added to the manuscript, to display a summary of key or landmark trials to be considered when treating advanced HER2 positive and advanced triple negative breast cancers, and special considerations for older adult patients.
2. We have now added some additional context following line 93, in keeping with your comment. Given that primary breast surgery is not standard of care in the metastatic context, we agree that patients should be considered for locoregional management strategies (be it surgery or RT) based on clinical context, symptom burden, and after multidisciplinary discussion – just as would apply to a younger patient population as well.
3. While this is a very interesting point, and certainly can present a clinical challenge - there is no special treatment recommendation for elderly men with breast cancer or older obese patients. This has been updated in the manuscript (lines 100-103 and 135-138). Obesity in particular presents a significant comorbid burden of illness and can majorly impact mobility, and can be a significant challenge in this patient population.
4. Thank you for this suggestion, a table detailing pertinent ongoing research efforts has now been included. See new table 5.
5. This section has now been updated to include specific discussion about the relevant ongoing studies detailed in point #4.
6. While we agree that it is also highly relevant to discuss therapeutic options beyond first line in this patient population, we have chosen to discuss this mainly in the body of the manuscript (and other above tables). This is because inclusion of 2L and 3L strategies in what was originally table 2, now table 4 in the revised manuscript would make the table too large, and less user-friendly for quick reference by adding about 3-6 rows of data. We hope that discussion in the body of the manuscript can give sufficient information to interested readers about selecting later lines or therapy.

We appreciate your thoughtful comments, and hope that these corrections are to your satisfaction. We agree that these help to improve the quality of this paper.

Sincerely,

The Authors

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your comments re prior review - thank you for the work done on the current version which includes detailed discussion on cognitive function, tables on ongoing studies and a highlighting that this is a growing area of clinical interest. Table 4 in particular is excellent and readily translatable to educational material. Well done

Reviewer 3 Report

Comments and Suggestions for Authors

I would like to endorse your publication. However, the latest revision should be more readable. Please present a more concise version as the final.