Reviewer's report
Title:Molecular subtype analysis determines the association of advanced breast
cancer in Egypt with favorable biology
Version: 2Date:14 June 2011
Reviewer: Lisa Baumbach
Reviewer's report:
In the paper by Salhia, et al, “Molecular subtype analysis determines the
association of advanced breast cancer in Egypt with favorable biology”, the
authors report their investigations of 200 tumor specimens obtained from Egypt
by performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry to
determine distribution of molecular subtypes of breast cancer (BC). The samples
are from two different cities – Cairo (large urban center) and Minia (large rural
center). The overall study importance is that results indicate that the Luminal A
subtype (ER+/PR+/Her2-), which is associated with favorable prognosis, was
detected in over 55% of Egyptian cases examined. These statistics are very
different than BC from bordering African cases, in which Triple negative and
basal breast cancer (both associated with poor prognosis) are overrepresented in
women from different parts of Africa (published studies). The basal-like subtype
was still detected in 11% of the Egyptian cases.
Particularly striking is the high percent of advanced disease detected in the
Egyptian cases. In Table 1c, Tumor characteristics by site of origin, there is very
clear evidence for advanced disease at both Egyptian sites. Tumor samples were
overwhelmingly positive for lymph node positivity; large size (> 2.0 cm), and
advanced histological grade. The authors conclude that although Egyptians
appear to have favorable underlying biology, they have advanced disease at
diagnosis. This is, of course, the key clinical dilemma - to have BC that presents
at advanced stage, but has a potential favorable outcome with proper hormonal
therapy. This manuscript raises a remaining important clinical issue which has
not been previously addressed.
The primary importance of the paper is that it is one of the first studies to directly
investigate molecular subtypes in a subset of Egyptian samples. Due to the
proximity of Egypt to Africa, it is a natural assumption that the molecular BC
subtype distribution would be similar. This paper clearly shows, that at least by
IHC, these appear to be different. The authors conclude that their data set
suggests that Egyptians would largely profit from early detection of their disease,
as the underlying biology is largely in the treatable category (hormone receptor
positive). Therefore, the paper may well raise some awareness in the public
health sector pertaining to BC screening and early detection practices in this
community.
Having said this, there are still some weaknesses/missing information with the
paper which need attention/correction before publication.
Suggested improvements to the manuscript:
(1) The authors make a significant point that the samples are from two different
cities in Egypt , yet, very little information is given about these cities- size,
distance apart, any evidence in differences with environmental exposures??
Information about differences in socioeconomic status? Anything known about
incidence of BC in these two areas? All of these points would be of interest to the
reader and merit further discussion. Also, if the authors hypothesize there might
be differences (even slight) in the distribution, grade, etc, of the tumors form the
two different settings (urban vs. rural), then this information may be very
important, as it is well known that BC is a multi-factorial disease. This is exactly
why further discussion of these points is needed. For example, if the only
difference between the two settings is time to access to care (which may not be
known, but may be inferred from other demographic indices), then these
findings/implications have major public health ramifications.
(1a) The reviewer believes an improvement in the paper would be an additional
figure, a map
of the African continent, indicating where the respective Egyptian cities are
located.
The authors also need to address ancestry of the study populations, especially if
they are
thought to be of African origin, and why the percent distribution of BC molecular
sub-
types differs from neighboring or close-by African populations that have been
similarly
analyzed.
(2) The authors should also discuss the major limitation that no gene expression
microarrays were done in this study- only IHC –and that gene expression
microarrays would be the next step in the study, with the goal of determining if
there are differentially expressed genes in the Luminal A subtype (compared to
published literature) in Egypt, that makes it apparently more aggressive in the
Egyptian population.
(3) Several tables need better font. In the reviewer’s version, Tables 1a and 1c
are hard to read; Table 4 may not be necessary.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.