PONE-D-19-31211

Prognostic value of the Residual Cancer Burden index according to breast cancer subtype: validation on a cohort of BC patients treated by neoadjuvant chemotherapy.

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: This is a well-written manuscript with a worthy study goal. My only comment would be that the TILS data seemed a bit out of place in this study. I would focus this solely on the validation of the RCB index. Data related to LVI and TILS association with RCB is probably saved for a separate manuscript.

Reviewer #2: This article is an independent validation study of the RCB index within the main subtypes of breast cancer and with long-term follow-up. Furthermore, it addresses the independent contributions of lymphovascular invasion (LVI) and tumor infiltrating lymphocytes (TILs) in the residual tumor bed. The methods and results are clear.

It appears form the K-M plots that there were few events in the 29 patients with luminal subtype who had pCR or RCB-I (5 RFS events and 2 OS events). It might be that there was insufficient statistical power to observe a difference in that subset - something to discuss with the statistician.

The LVI result is important and adds new information to the field. I note that a small subset had missing data and so the LVI status was imputed from other variables. It would be helpful to know whether the significance of LVI still holds when the analysis is restricted to the majority subset where LVI status was reported b the pathology review.

Some minimal edits to consider:

Page 6, Pathologic Review, 1st sentence. This sentence could be more clear. Presumably the slides from both the pre-treatment core biopsy and the post-treatment resection specimen were reviewed in all 717 cases.

Page 7, last sentence: Was this the Chi-square test?

Reviewer #3: It would be helpful to compare your findings to the findings form the Meta-analysis of > 5000 patients incl 5 and 10y EFS presented at SABCS 2019 GS5-01.

It would be helpful to include details about sampling of the breast specimens included. The SOP for RCB was published in 2007. The cohort starts in 2002. How did the sampling of the retrospectively reviewed surgical specimens differ form the RCB SOP? How did this affect calculation of the RCB scores.

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Reviewer #1: No

Reviewer #2: Yes: W. Fraser Symmans, M.D.

Reviewer #3: No

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Prognostic value of the Residual Cancer Burden index according to breast cancer subtype: validation on a cohort of BC patients treated by neoadjuvant chemotherapy.

PONE-D-19-31211R1

Dear Dr. Reyal,

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

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With kind regards,

Tina Hieken, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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