Reviewer ’s report  
 
Title: Independent risk factors for axillary lymph node metastasis  in breast cancer patients with 
one or two positive sentinel lymph n odes 
 
Version: 0 Date: 20 Oct 2019  
 
Reviewer: Dimosthenis Chrysikos  
 
Reviewer's report:  
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The purpose of this study appears to inv estigate independent risk factors in a Chinese population 
of breast cancer patients, with one or two positive sentinel lymph nodes  
Overall, the manuscript is very well organized and it has a central theme.  
Molecular profiles are acknowledged promising prog nostic factors, nevertheless the status of the 
axillary lymph nodes at the time of diagnosis has been accepted as one of the most important 
prognostic factors for the overall and disease -free survival of patients with breast cancer.  
There are some crucial points to be mentioned:  
 
1 First, familial cancer history or hereditary breast cancer (BRCA1 , 2) must be discussed in the 
observed population or alternatively evaluated in the statistical methods that were used.  
 
2 Please discuss other risk factors for axi llary lymph node metastasis that are published in the 
literature. For instance, presence of perineural invasion, lymphatic vessel invasion, age below 40, 
and an extensive intraductal component of more than 25% etc.  
 
3 Please discuss the rate of complication s not only after ALND but after SLNB. SLNB practice 
has reduced the complications of shoulder stiffness, pain, and lymphedema but it has a low 
incidence of such complications.  
 
4 The trend for breast cancer treatment is currently shifting towards minimizin g axillary surgery, 
even in the presence of sentinel lymph node (SLN) involvement.  
Authors must discuss:  
 
-The Z0011 trial that has demonstrated that the 10 -year overall survival (OS) of patients with 1 
to 2 sentinel lymph node metastases (SLNM) treated wi th SLNB and whole -breast irradiation is 
non-inferior to the OS of patients with no palpable axillary adenopathy clinical T1 -T2 invasive 
breast cancer (IBC) treated with axillary lymph node dissection (ALND).  
 
-The AMAROS trial that found further evidence to  show that the axillary recurrence -free rate of 
patients with SLNB -proven metastasis treated with radiotherapy is non -inferior to those treated 
with ALND.  
 
-The ALMNAC validation study, which enrolled patients with higher tumor grade that had 
higher false negative rate of SLNB; and the risk of patients with a missed axillary disease after a 
negative SLNB is 2.2%  
 
5 Was radiotherapy of the axilla performed in the study population ?  
 
6 There is a trend in the literature with predictive nomograms in such studies . Please refer to 
similar studies.  
 
7 The research design and the applied methods are of a satisfactory level  
 
8 In the statistical methods:  
 
-Logistic regression analysis may used to identify risk factors associated with a false -negative 
(FN) result.  
 
-Cox regression model may be used to estimate the hazard ratio of factors affecting disease -free 
survival (DFS) or overall survival (OS).  
The small number of patients may have affected the statistical power of this study.  
Finally, the information in the ma nuscript is sufficient and merits publication, after major 
revisions.  
 
Are the methods appropriate and well described?  
If not, please specify what is requ ired in your comments to the authors.  
 
Yes 
 
Does 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.  
 
Yes 
 
 
 
 
 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publi cation of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you curr ently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any  other financial competing interests?  
 
6. 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.  
 
I declare that I have no competing interests  
 
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