PONE-D-22-18837Survival outcomes of breast cancer patients with recurrence after surgery according to period and subtypePLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Partly

Reviewer #2: Partly

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript titled ‘Survival outcomes of breast cancer patients with recurrence after surgery according to period and subtype’ aimed to compare survival outcomes in BC patients between two periods of time o identify the factors associated with post-recurrence survival and overall survival and changes over time in the duration of survival after recurrence. Following comments could be helpful for authors.

Minor comments:

- Don’t mention the definition of period1 and period2 multiple times (lines 21,25,55, 63, 169)! Mentioning once would be enough!

- Your sample size is 2,407, so report it in abstract and method as your sample size as your analysis is based on that.

- It seems that there is an abbreviation in the literature stands for post-recurrence survival (PRS).

Major comments:

- There is a lack of proper rationales in introduction part. Why this study is important?

- SAR should be defined from the time of recurrence to death/last follow up. OS is also defined time from diagnosis to death/last follow up time.

- What about eligibility criteria! Is your study restricted to age (e.g., 18-77), those who had not second recurrence or metastasis etc.

- If study aimed to see improvement in treatment in patients who had recurrence, the time of treatment is of importance. If so, the treatments for patients with recurrence should be considered as well! You don’t know is this the effect of treatments before recurrence or after the recurrence. This bias can affect the result. Were patients received the treatment after their recurrence? There is no information in the manuscript to support this! The treatments mentioned in table 2, are received by patients after recurrence?

- In table 2, comparison results showed that in some pathologic variables, there are significant differences between two periods (e.g., T stage, Nodal status, HR etc)! It seems that you might need to match comparison groups. The question is that are they comparable?

- Your sample size covers recurred patients (your title), right? while you have results based on overall survival which includes interval time from diagnosis to death/last follow up!

- Be clear on your sample size! It looks Analyses were performed based on recurred sample! If you are analyzing 17,776 patients, mention the sample of analysis in table 4 and 5.

- Why didn’t you use trend analysis to see the changes over time?

Reviewer #2: Sept 5, 2022

Title: Survival outcomes of breast cancer patients with recurrence after surgery according to period and subtype

This paper presents a study to analyze and compare the survival rates of recurrent breast cancer patients in Korea between two periods (2000–2007; 2008–2013) and to identify the factors associated with outcomes and changes over time in the duration of survival after recurrence. However, there are questions that limit my enthusiasm of the paper, as outlined below.

1. Authors include the patients with unknown clinical variables e.g., stage, histology, etc. Why not removing these patients? If for any clinical and biological reason, this group named as “unknown” is important and would like to assess the effect of that in analyses, still not correct analysis was applied. Authors considered chi-squared method to do the association which will have low power in this scenario, and the non-parametric Fisher exact test is the correct method to be applied.

2. Authors did mention that multivariate Cox model was applied, and I couldn’t follow in which step this method was applied. I already saw the findings using univariate Cox model.

3. Please keep the HR estimate along with p value to report findings.

4. Table 3: Please add appropriate test to assess the association between type of recurrence and year of recurrence.

5. Figures 2 and 3: How about adding supplementary figures to show the KM and log-rank test using OS across all four subtypes and the same test for SAR.

6. Tables (e.g., 4 and 5), for example for some categorical variables e.g., age, T stage, etc., we have the p values and other statistics for each category, while a p value for that given variable (e.g., age, T stage). I couldn’t follow how the p value was computed.

7. In addition, authors only considered clinical data, while adding molecular data along with clinical data to assess the association with OS or SAR can make the paper much more interesting along with this fact it can be fit better for PLOS ONE journal requirement.

Reviewer #3: 1. Using anti-hormonal therapy instead of hormonal therapy is not common. Even though It is not incorrect, it is suggested to change it.

2. Table 3: According to data in table 3, no patient had a locoregional and systematic recurrence. While the co-incidence of outcomes is possible.

3. Line 101: You have presented that the follow-up duration from the time of relapse ranged between 0–223.4 months. Since the data is pertaining to 2000-2013 and they have been recruited into the database from 2017 to 2021, one expects that their follow-up time is not zero. Would you please explain more about this data?

4. Please define the statistical tests which were used in the analysis of data presented in lines 131-135.

5. Line 134-135: In this sentence, “… the median 5-year OS rate 135 from the period I (97.5 months) to period II (114.4 months)”, you have not presented any survival rate, and the sentence needs an edition. Those values are the median survival durations.

6. Tables 4 and 5 are huge boxes of data and are hard to use. The p-values can be deleted, and the significant HR (0.95 CI)s can be bolded.

7. Line 191: regarding this sentence and the following explanation, “In multivariate analyses, age at diagnosis was independently associated with…” we should notice that independent association of variables is studied in univariate analysis. In multivariate analysis, the effect of each variable is dependent on the effect of other included variables in the regression model.

8. Line 208: “chemotherapy after recurrence was significantly associated with survival outcomes…”. It is not clear whether it was associated with better or worse survival?

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Shahpar Haghighat

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Attachments

Attachment

Submitted filename: comments_06092022.docx

Survival outcomes of breast cancer patients with recurrence after surgery according to period and subtype

PONE-D-22-18837R1

Dear Dr. Lee,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Yasunori Sato

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: No

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Title: Survival outcomes of breast cancer patients with recurrence after surgery according to period and subtype

Authors addressed all the comments. Thank you

Reviewer #3: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: Yes: Shahpar Haghighat

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