-->PONE-D-25-55193-->-->Real-world implementation and cost impact analysis of Oncotype DX testing in early-stage breast cancer-->-->PLOS One

Dear Dr. Mäenpää,

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Academic Editor

PLOS One

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Reviewers' comments:

Reviewer's Responses to Questions

-->Comments to the Author

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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: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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-->5. Review Comments to the Author

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Reviewer #1: The study, like the TAILORx study, suffers from a major issue. This is that a control group is missing that was treated without receiving an Oncotype testing but assuming that an ODx score was present. This control group would show that

a) Oncotype testing is essential rather than being a tool that can be used add on and overtakes a medical decision, that may also be made if a treained team of pathologists and senologists work together and bring in their experience in concert with cheaper diagnostic tools (IHC and classical stainings combined with clinical observatins).

b) oncotype Dx is more than a diagnostic placebo

c) Oncotype Dx is indeed cost efficient, because if A9 would manifest and it should become clear that Oncotype testing can be replaced by classical methods even the 3180 € can be saved, which would also have a remarkable effect on health economics.

Thus, the study has no added value which is typical for the majority of clinical Oncotype studies for which at least one author have received speaker honorary from Exact Sciences or predecessor organisations.

However, I would would reconsider the study if a proper control group will be included.

Reviewer #2: The manuscript is well written with clear ideas and addresses an important topic on the clinical and economic impact of Oncotype DX testing. However, methodological details and patient selection criteria should be clarified.

The economic analysis is useful, but the assumptions used in cost calculations should be explained more clearly.

I recommend adding a schematic figure of the Oncotype DX assay (21-gene panel) or workflow would improve understanding of the test.

I also recommend analysing the relationship between tumour grade and treatment decisions based on the Oncotype DX recurrence score.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PONE-D-25-55193.pdf

-->PONE-D-25-55193R1-->-->Real-world implementation and cost impact analysis of Oncotype DX testing in early-stage breast cancer-->-->PLOS One

Dear Dr. Mäenpää,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jul 16 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:-->

• A letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

-->

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only  the individual author can complete the verification step; PLOS staff cannot  verify ORCID iDs on behalf of authors.

We look forward to receiving your revised manuscript.

Kind regards,

UDAYAN BHATTACHARYA

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Authors,

Thank you for submitting your manuscript, "Real-world implementation and cost impact analysis of Oncotype DX testing in early-stage breast cancer."

The manuscript has been evaluated by external reviewers. Overall, this study addresses an important and clinically relevant topic and provides valuable real-world evidence regarding the implementation of Oncotype DX testing in routine multidisciplinary breast cancer care. The strengths of the work include the use of a consecutive patient cohort, a detailed description of the implementation pathway, and the assessment of both clinical and economic outcomes within a publicly funded healthcare system. The manuscript also provides important national data from Finland, where real-world evidence regarding genomic assay implementation remains limited.

The reviewers raised concerns regarding patient selection, the absence of a non-Oncotype comparator cohort, and the assumptions underlying the economic analysis. After considering the reviewers' comments and the authors' responses, I am satisfied that the primary objective of the study is to evaluate the real-world implementation and clinical impact of Oncotype DX testing rather than to further validate the assay itself. The clarifications provided in the revised manuscript have strengthened the methodological transparency and interpretation of the findings.

Before acceptance, I encourage the authors to further emphasize the limitations of the economic analysis. In particular, the projected societal cost savings appear to be driven largely by assumptions regarding productivity losses and duration of sick leave among chemotherapy-treated patients. As patient-level economic data were not available, several cost estimates were necessarily based on assumptions and average unit costs. While the sensitivity analyses are helpful and support the overall direction of the findings, the Discussion would benefit from a more explicit acknowledgement that the magnitude of the estimated savings may vary depending on real-world employment patterns, return-to-work timelines, and healthcare utilization. Accordingly, conclusions regarding economic benefit should be presented as projected estimates under the assumptions of the model rather than as directly observed cost savings.

Subject to these minor revisions, I believe the manuscript makes a useful contribution to the literature and will be of interest to clinicians, healthcare administrators, and policymakers involved in personalized breast cancer management.

I therefore invite the authors to submit a revised version addressing the remaining minor points.

Sincerely,

Academic Editor

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

-->

Real-world implementation and cost impact analysis of Oncotype DX testing in early-stage breast cancer

PONE-D-25-55193R2

Dear Dr.  Mäenpää,

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.

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Kind regards,

UDAYAN BHATTACHARYA

Academic Editor

PLOS One

Additional Editor Comments (optional):

Dear Dr. Mäenpää,

I am pleased to inform you that your manuscript, "Real-world implementation and cost impact analysis of Oncotype DX testing in early-stage breast cancer" (Manuscript Number: PONE-D-25-55193R2), has been formally accepted for publication in PLOS ONE.

The revisions made to the manuscript have satisfactorily addressed the remaining points raised during the review process. We appreciate your diligent work and responsiveness throughout the evaluation of your paper.

The PLOS ONE production team will be in touch with you shortly regarding the final formatting requirements, proofs, and publication schedule.

Thank you for choosing PLOS ONE to publish your research. Congratulations on the acceptance of your manuscript.

Sincerely,

Dr. Udayan Bhattacharya

Academic Editor

PLOS ONE

Reviewers' comments: