PONE-D-24-45078Dismal Pathological Response to Neoadjuvant Therapy in Stage III Breast Cancer Patients in Tanzania: A Retrospective ReviewPLOS ONE

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Reviewers' comments:

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Comments to the Author

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

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Reviewer #1: No

Reviewer #2: Yes

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

Reviewer #1: N/A

Reviewer #2: Yes

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

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Reviewer #1: Yes

Reviewer #2: No

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4. 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 #1: No

Reviewer #2: 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: None of the patients received targeted therapy in the NAT setting. This is a retrospective study and without targetted treatments, we could not conclude the results. There is a selection bias in this cohort.

Reviewer #2: I am thankful for the opportunity to review the manuscript titled ‘Dismal Pathological Response to Neoadjuvant Therapy in Stage III Breast Cancer Patients in Tanzania: A Retrospective Review’. This is a well written manuscript from an LMIC, highlighting low PCR rates with NACT in stage 3 breast cancer patients undergoing modified radical mastectomy. The methods are appropriate for the study question at hand and the results are easy to follow. The authors demonstrate sound reasoning regarding potential reasons for low pCR rates in their cohort within the limitations of the study. I have few comments below.

ABSTRACT

Conclusion: States that ‘a relatively poor pathological response was observed’, however a comparison is not provided? Poor compared to what? Western counterparts? Please specify.

MAIN TEXT

Introduction

- Line 69: ‘Despite the relatively low incidence of BC in Africa, mortality remains high, and overall survival rates are disproportionally lower in SSA’ - A comparison is not provided again. Relatively low incidence compared to what? Also, would be better to specify the incidence and overall survival rates for clarity rather than providing a generic statement.

Methods

- Please define the duration of neoadjuvant therapy (number of cycles and lines)

Results

- Figure 2 is redundant and maybe safely omitted

- Was a modified radical mastectomy (mastectomy + axillary lymph node dissection) performed in all patients without an attempt at sentinel lymph node biopsy/targeted axillary dissection? This may reflect a difference in management from Western populations where there is an emphasis on de-escalation of complete axillary dissection.

- Do the authors have data regarding completion of planned chemotherapy cycles? This is an important covariate and should be compared between the two study groups.

- Do the authors have data regarding grade chemotherapy-related toxicities? While they document higher pCR rates with more aggressive neoadjuvant therapy (AC-T vs. AC or AT), it would be worthwhile to explore if this was at the expense of higher significant adverse rate. This may also be a reason for discontinuation of neoadjuvant treatment.

Discussion

- Can the authors comment about the utilization of screening mammography in Tanzania? What proportion of the cases were screening detected? In the absence of widespread screening, tumors are more likely to present at advances stages, which might be possible in their cohort

- Lines 257-268: In addition to recommending strategies for early detection, can the authors comment about measures to make modern neoadjuvant therapies available? For example, immunotherapy (Keynote 522 regimen) has been incorporated as the standard of care for neoadjuvant treatment of TNBC. Are there any measures which may be undertaken at a systems level to make these available in a LMIC setting?

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Reviewer #1: No

Reviewer #2: Yes:  Varun Bansal

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Dismal pathological response to neoadjuvant chemotherapy in stage III breast cancer patients in Tanzania: A retrospective review

PONE-D-24-45078R1

Dear Dr. Kivuyo,

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,

Daniele Ugo Tari, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #1: All comments have been addressed

Reviewer #2: 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 #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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 #1: Yes

Reviewer #2: No

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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 #1: Yes

Reviewer #2: 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 #1: The early stage of diagnosis is associated with a complete pathological response, indicating a need to improve diagnostic strategies to capture patients in the early stages to improve outcomes. This manuscript was revised according to the reviewer suggestions.

Reviewer #2: I believe my comments have been addressed adequately. Thank you for your making the necessary modifications.

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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 #1: No

Reviewer #2: Yes:  Varun V. Bansal

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