Reviewer’ s report
Title: Androgen receptor expression in a Sri Lankan patient cohort with early breast carcinoma
Version: 2Date: 20 Jun 2020
Reviewer's report:The manuscript by Wijesinghe et al is describing the expression status of androgen receptor in a
group of early breast cancer patients and further analyze its association with clinicopathologic
characteristics and survival.
The following are some comments for the consideration by authors:The manuscript requires major revision for language.Results sections requires major revision the way it is written. I suggest dividing it into sub-
sections, especially when presenting survival data.
In abstract, authors mentioned a lack of association between androgen receptor expression and
clinical characteristics, however there is no earlier mention to these characteristics.
I highly recommend re-writing the study findings in Abstract and focus on most important ones, as
they are not easy to follow the way they are currently presented.
In introduction, there is no clear rationale to considering androgen receptor (AR) as a potential
biomarker in breast cancer. Having done such studies in other countries is not a strong rationale to
conduct the current study. Expand your discussion on AR and the rational to investigate this
marker in breast cancer patients.
In Methods, sample selection indicates enrollment of patients with invasive carcinoma. However,
in Results, some findings correlate with in situ carcinoma of the breast. Please verify.
Provide a clear inclusion and exclusion criteria for breast cancer patients enrolled. Were these
patients selected randomly from a bigger cohort, or the selection followed convenient sampling?Please add details.
Provide the number of patients who were excluded from the study who do not meet your inclusion
criteria.
Who did the assessment of tumor margins and the histologic type for the tumor sections?
pathologists? Or was this data retrieved as a documented data? Please make this clear in yourmanuscript.
For tumor vascularity, how the grading was determined? If this is following some published
grading protocols, please cite your reference in the manuscript.
I am little confused about the expression status for ER, PR, and HER2. It is my understanding that
you already performed ER, PR, and AR IHC to your samples. I believe that the expression of ERand PR should be already available and can be retrieved as data along with HER2. So, if you re-stain for the expression of ER and PR, did you do the same with HER2?
Please note that despite the lack of ki67 data in your case, some luminal B tumors are HER2-
positive, thus you can identify some tumors as luminal A or luminal B based on the expressionstatus of the three receptors. Please verify this in Methods.
Please explain how overall and disease-free survival were determined by interviewing patients? I
am little confused if this was a retrospective analysis to archived tumor samples or if you alreadyincluded patients who were newly diagnosed with breast cancer. Please add details of patientrecruitment.
Please explain the way you did data retrieval. For example, for demographics, did you retrieve
data from medical records or electronic database? Alternatively, did you record the data byinterviewing patients? For the clinicopathologic data, did you refer to Pathology Reports generatedby the Hospital?
Provide the name of the statistical software program used for analysis.The way data is presented in Table 1 is not very illustrative. Please provide frequency and
percentages. The used letters are complicating the Table, I don't think they are well placed.
You have dichotomized expression status for AR as positive and negative. What are the scores
given in your Figure 1? Please describe in Methods and/or Results.
I think you need to re-number your Tables and make the IHC Table as number 1.
There are significant findings in Table 1 regarding expression of AR and tumor treatment. Please
highlight and discuss in text.
Add a Table that clearly summarizes demographics and clinical characteristics for you enrolled
patients. Please provide age, body mass index, clear TNM stage, nodal status, histology type,receptor status, molecular subtypes, lymphovascular invasion, histologic grade, treatment, surgery,and all other pertinent information to better understand the population studied in this analysis.Were patients with metastatic disease excluded? If yes, explain the reasons.
In Results, some variables are being dichotomized for the goal of conducting statistical analysis.
Please indicate this under Methods and explain how the dichotomization was determined.
The flow of the manuscript is not smooth. So, you mention Table 3 and then go back to Table 1.
Please smooth out.
Page 9, Line 5-10: 'None of the clinical data studied showed any significant association with either
AR-positive or negative status (p>0.05).'What Table reflects these findings? What are these clinical data? The same statement is mentionedin Abstract as well, please review.
Page 9, line 10-14 'Of the pathological features studied, lower nuclear grade (nuclear grade 2 vs 3)
(p=0.037) and lower mitotic count (1/2 vs 3)(p=0.036) were significantly associated with AR-positive status.'It is my understanding that the mitotic index is a factor when determining tumor histologic grade.
Please review the data above.
Page 9, line 14-17 'However, there was no association with Nottingham grade, tumor and nodal
stages and the TNM stage (p= 0.484, 0.613, 0.436, 0.830 respectively).'Rephrase.
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NoAre the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
YesAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
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