Title: Interaction of reproductive tract infections with estrogen exposure on breast cancer risk
and prognosis
Version: 3 Date: 21 Feb 2023
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is indeed a study which offers results in a missing literature
point. The results are novel and important in the pathophysiology of breast cancer.
The authors use an impressive number of cases which render their results even more important.
They manage to show the inverse correlation of reproductive system infections with breast
cancer, which adds an important information in the literature.
There are few points to ameliorate, mostly better explain the selection of cases - criteria for case
control studies should be strictly defines.
REQUESTED REVISIONS:
- The authors should better define the criteria during the selection of the case control study.
These studies are among the most difficult to design and appropriate statistical analyses should
define the proportional scores for selecting the controls. The authors should thus explain better
the selection of their controls, and comment clearly on the limitations of their selection.
- On the same line, it is not clear the medical history of the controls (and cases): history of
other cancers? autoimmune diseases? HPV? family history of breast cancer? There are several
parameters (factors associated with cancer) that are not addressed in the MM section and in the
limitations.
- the case cohort and the patient cohort don't have similar patients, given that the period time
of diagnosis is partially the same?
- the questionnaire used should be provided at least as sup file.
- the questions regarding infections are not clear. What kind of infections were considered
as positive? Those diagnosed by microbiology? Those suspected by the patient but maybe
not treated? Those diagnosed by the generalist and the gynecologist and treated even without
microbiology confirmation? Did that include urinary infections only? What bout HPV?
- a MAJOR missing issue is contraception, no relative question???
- the discussion should clearly comment on the lack (or presence) of epidemiological studies
with the same question.
- the discussion should better address the pathophysiology behind their findings: studies in
animals could be helpful in this point.
- minor English amelioration is needed."