Title: The association between mammographic density and breast cancer risk in Chinese
women: A systematic review and meta-analysis
Version: 1 Date: 30 Nov 2023
Reviewer's report:
A good review and meta-analysis examining te association between mammographic density and
breast cancer risk in Chinese women. Its publication will add to the literature of breast density
of women in China, but there are issues with presentation and clarity of methods, results and
discussion that should be dealt with before further consideration.
Detailed comments:
Introduction
- The manuscript started with the breast cancer in the world, which is indirectly related to your
topic of Chinese breast cancer, it would be best to have use China’s data instead, such as https://
doi.org/10.1111/ajco.13958, https://doi.org/10.1007/s10549-016-3947-0
- “Although the overall incidence of breast tumour in China is lower …higher than the global
average”: references are needed for statistics and the comparison with global average.
Materials and methods:
- “it was conducted by two independent reviewers (S.B. and D.S.) …resolve disagreements.”:
The author did not describe clearly that if the independent review and consensus/discussion
were performed for each of the process from study selection to quality assessment. For example,
did either of these two reviewers go through title and abstract screening or a certain amount/
proportion of all studies were reviewed.
- Search strategy:
o the search strategy is not detailed in the appendix A because the author put all the MESH
and keywords together. It would be more appropriate to list them separately for each database.
Because the MESH and keywords are likely to be slightly different in each database. This is
critical for reproducibility purpose.
o It is great to use Wanfang database in this study since the population in this review is women
in China rather than Chinese women in westernised/developed countries. It is expected there
are many studies conducted in China. However the author did not specify if the literature search
was conducted in English (via English interface) or in Chinese (via Chinese interface) or both to
capture all the available studies? Because the search results could be somehow different, such
as in the CNKI database.
- Lack of study selection process. A PRISMA checklist will be helpful.
- Inclusion and exclusion criteria: the description needs to be precise for the study population
because the authors specifically focused on “women in China” rather than “Chinese women”.
Besides, the country/region may need to be specified as well, for example, did the author only
include women from mainland China, or also include women from any Special Administrative
Regions?
- Quality assessment: the description in the paragraph (i.e. the AHRQ instrument, and the
MINOS  instrument) was inconsistent with the appendix C-D.
- Statical analysis:
o “women with breast density BI-RADS II, III, and IV were compared to women with breast
tissue BI-RADS I by …..”: Authors compared BIRADS 2,3 and 4 to BIRADS 1, respectively;
however the description is not precisely here which is easy to be misinterpreted as combined 2-4.
o The analysis for cross-sectional studies was not mentioned.
o Lack of description for the analysis of two-category comparison.
o “we combined RRs across studies and then …”: I don’t understand what the author mean by
“combined RR”. Did all these included case-only studies reported RR as the effect measure and
you “combined” them?
Results:
- Included studies:
o “an additional investigation was found”: do you mean another study/report was found?
o Figure 1: strongly suggest to use the latest PRISMA Flow Diagram (http://prisma-
statement.org/prismastatement/flowdiagram.aspx?AspxAutoDetectCookieSupport=1)
o Figure 1: I don’t understand what the author means by “unrelated content” and why authors
“can’t get data”.  Authors need to precisely describe the reasons why certain report are removed
from full-test assessment. Also, 1 commentary was removed, did the author remove it purely due
to the article type? What if the commentary contains relevant data but reported in the format of
commentary/research letter. Because lots of primary studies (particularly the secondary analysis)
tends to be reported as short article/commentary/research letter.
- Study characteristics:
o “non-cases of breast cancer” is an inappropriate description, suggest cancer-free women/
population.
o “undiagnosed breast cancer” is easy to be mis-interpreted, suggest women who were not
diagnosed with breast cancer. Again, the use of English words needs to be precise.
o “crude data”: please define what crude data refer to in your study.
o “twelve studies controlled for the most important confounding factor of age/BMI, and four
studies only adjusted for age”. This sentence is confusing to readers. Please rewrite it.
- Quality assessment: this section is very hard for readers to follow.
o The scores of the quality assessment are meaningless without further explanation. For example,
what is the max score or if there is any threshold for low/middle/high risk, .etc.
o Authors need to explain what the marks (e.g. [1]) mean in this section.
o Some reasons have proportions but others do not, and some have marks and others not. Please
keep them consistent.
- Results of meta-analysis:
o Fig 2-5: “p=0.000” is not an accepted form. Exact P values should be given unless P is less
than 0.001. If P is less than 0.001, write “P < 0.001”.
o I2 and p values also need to be reported in the text while reporting OR/RR and 95%CI.
o I can only see the p values for heterogeneity in figures and could find the p values for overall
effect.
- Publication bias:
o Supplementary table 1 is not provided.
o Please put all the supplementary tables and figures into one file and provide figure captions for
each figure. The current supplementary figures without captions did not provide any information
to readers.
Discussion:
- It is not needed to report 95%CI in discussion as authors already clearly reported in Results.
- “the association between MD and breast cancer risk was significantly weakened or even
disappeared in Chinese women”. This statement can not be concluded from your results. Because
the association between MD and breast cancer risk was not or weakly found in women in China,
how come it “was significantly weakened or even disappeared”.
- Ref 26 is a bit out of dated, it would be best to use a more updated report or latest data of breast
cancer incidence in China and westernized countries/region, such as https://doi.org/10.1111/
ajco.13958
- “It can be seen that Chinese women both have denser mammary glands and lower incidence
than European and American women.” This statement can not be concluded from the previous
sentence which summarizes a study in New Zealand (ref 27). Because the New Zealand study
reported Asian women rather than Chinese women although Chinese women is one of the
predominant group in Asian women in that study. Also, Asian women living in westernized
countries can not be treated equally as women in China due to ancestry status (immigrated/
by birth) and change of life/eating style and other factors. A more appropriate study which
examined MD difference between women in China and westernized country is this one: https://
doi.org/10.1111/ajco.13763
- “Therefore, the history of estrogen replacement therapy …Asian women.” This sentence should
be the conclusion of the last paragraph rather than the start of this one.
- The discussion of obesity is less convictive, because the authors used data of Asian women
and/or Asian women living in westernized countries. As mentioned before, Asian women in
westernized countries can not be treated equally as the population in your study “women
in China”. Besides, the MD in Asian women from Asia could be different from the MD
profile in women in China due to a variety of ethnicity/race in Asia. The study findings from
Asian women can not be directly applied to women in China without further investigation.
For example, these papers reported negative association (https://doi.org/10.1155/2019/4910854,
https://doi.org/10.1186/s12885-023-11444-7, https://doi.org/10.1111/tbj.12963) between BMI
and MD for women in China and these papers reported higher percentage MD for women in
China when compared to women in Australia (https://doi.org/10.1111/ajco.13763).
- “a considerable portion”: do you mean a considerable proportion?
- “In addition, studies have demonstrated that menopause causes a decrease in mammographic
density”: The term of “causes” is inappropriate because none of the cited studies examined
cause-effect relationship between menopause and MD. Instead, these studies in fact examined
the associations. Also, these three references are outdated, I am sure there are relatively recently
published papers on similar topic and used women in China or at least Chinese women.
- Again, ref 43-44 did not focus on population in China.
Conclusion:
- The conclusion is vague and lacks the most important findings from the meta-analysis. The
conclusion needs to be elaborated and needs to be a bit stronger. The final two sentences here
is good about MD prediction model and associated factors in premenopausal women but can
you give any quick examples and then say why this matter? Briefly? Right now it reads more
like an Abstract conclusion.
Presentation and Language:
- There are grammar errors, many incorrect use of words/terms and inappropriate description/
statement/expression through the manuscript, which requires language editing before re-
submission. It is recommended to have an English-speaking author to review the manuscript or
use professional editing services.
- Please spell out all the abbreviations when it firstly shows in the main body (not in the abstract)
of the manuscript.