Reviewer’s report
Title: 
Prediction of distant metastatic recurrence by tumor-infiltrating lymphocytes in hormone receptor-
positive breast cancer
Version: 
2 
Date: 
04 May 2021
Reviewer's report:
In this manuscript, the Authors sought to investigate the correlation between tumor-infiltrating
lymphocytes (TILs) density and recurrence site in hormone receptor-positive and HER2-negative
(HR+HER2-) breast cancer. To address this point, the Authors used needle biopsy specimens obtained
from all patients and subsequently they conducted morphological assessment of TILs. A total of 42
patients with breast cancer presented recurrence. In comparison to patients with TIL density, those with no
TIL density had less local recurrence whereas the distant metastases were significantly more. Additionally,
it has been shown that in HR+/HER2- breast cancer without chemotherapy, TILs could be used as
predictors of distant metastases. Based on these observations, Takada et al. conclude that TILs may predict
distant metastatic recurrence in stages I-II of HR+/HER2- breast cancer.
Although the topic is novel and interesting given the potential clinical utility of TILs in predicting distant
metastases, the findings reported by the Authors do not refer to stage I-II patients with breast cancer.
Consequently, the conclusions that have been drawn are not in line with the results of the present study.
Additionally, several points of this manuscript need to be improved. 
Please find a point-by-point description of the points that have to be enhanced:
-Abstract:
* It is not clear what is the association between TILs and distant metastases. Therefore, at least a linking
sentence with evidence that support such correlation and can corroborate the aim of the study is needed.
* The conclusion of the abstract does not reflect the results obtained in this study. It is concluded that the
findings regard the stages I-II of HR+/HER2- breast cancer; however, there are no indications in the
introduction, materials and methods, and the results of the abstract.
-Background:
* The authors should emphasize on the distant metastatic recurrence in HR+HER2- breast cancer patients. 
* The concept of patients' quality of life, which has been introduced in the background section, is not
strictly related to the topic. 
-Methods:
* There is no need to include all the patients that underwent surgery. Only the inclusion criteria are
necessary.
-Results:
* None of the results refers to the stage I-II breast cancer patients.
-Discussion:
* The authors discuss the literature but not the actual results obtained in this study.
* Given the important limitations of this study such as the small number of cases with recurrence, the
authors should explain how these constraints could be overcome.
-Conclusion:
* As abovementioned, the conclusion is not supported by the results.
-Figures and tables: 
* The quality of the micrographs (i.e. figure 2) is poor.
-General points:
* On the entire manuscript, the quality of the English language has to be improved in terms of grammar,
punctuation, and vocabulary.
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Declaration of competing interests
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following questions:
1
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organisation that may in any way gain or lose financially from the publication of this manuscript,
either now or in the future?
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applied for patents relating to the content of the manuscript?
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Do you have any other financial competing interests?
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Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your
reply is yes to any, please give details below.
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Is the study design appropriate to answer the research question (including the use of appropriate controls),
and are the conclusions supported by the evidence presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free from apparent
manipulation?
Yes