Reviewer ’s report  
 
Title: The Effect of Hormone Therapy on Quality o f Life and Breast Cancer Risk After Risk 
Reducing Salpingo -oophorectomy: A Systematic Review  
 
Version: 0 Date: 19 Dec 2016  
 
Reviewer: Beth Peshkin  
 
Reviewer's report:  
 
This is a well written, well organized and comprehensive review of a clinically important topic.   
 
Major Comment  
1. Background, line 68:  There are a couple of studies that call in to question whether RRSO 
reduces breast cancer risk in unaffected mutation carriers, especially in BRCA1 positive 
women (Kotsopoulos, JNCI 2016; Heemskerk -Gerritsen, JNCI 2015).  This shou ld be 
acknowledged here, and also in the intro and discussion (e.g., page 11).  Thus, the clinical 
question may not be whether HT negates breast cancer risk reduction in women who had 
RRSO, but whether it further increases it (and it appears that it does n ot).   
 
Minor Comments  
1. Background section, lines 63 -67:  Suggest substituting a primary reference rather than a 
review when citing the average risks of breast and ovarian cancer associated with BRCA1/2.  
2. Background, line 70:  Given the international readership of this journal, suggest citing more 
than the SGO guideline about recommendations for RRSO (e.g., NCCN in the U.S.; 
`European/ESMO guideline by Paluch -Shimon et al, 2016; BC Cancer Agency guidelines in 
Canada, etc.).    
3. Background, lines 77 -78:  Important to clarify that guidelines cited in references 9 -11 are 
not specific to mutation carriers, who may undergo menopause much earlier than women 
who experience this for reasons other than RRSO.  Thus, it is worth noting that the major 
guidelines specifically for women with BRCA1/2 mutations also state that short -term use of 
HT may be considered (e.g., NCCN, SGO, ESMO) - but they don't go so far as to say until 
the average age of natural menopause.      
4. Conclusion, line 294:  Would consider revi sing to: "clinicians and patients must carefully 
discuss the potential benefits of HT as well as non -hormonal therapies in improving 
QOL…"  Also, could remind readers that for women who opt for bilateral mastectomy, the 
concern about breast cancer risk is negligible.   
5. General:  Suggest clarifying in the background a reminder for readers that this review 
applies to women without a history of breast cancer.  (In clinical practice, survivors may be 
given some forms of HRT if they are far out from diagnosis  and particularly if their cancers 
were hormone receptor negative.)  Note also that the convention is to write BRCA1 and 
BRCA2 with no space between the acronym and number, and that the preferred way to refer 
to deleterious mutations is "pathogenic variant s." 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments t o the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain i n your comments to the authors.  
 
Yes 
 
Are 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 further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
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holds  or has applied for patents relating to the content of the manuscript?  
 
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