Title: Expression of inflammatory states in response to psychological distress in breast cancer
survivors and its relationship to subjective memory function complaints
Version: 1 Date: 01 Dec 2024
Reviewer's report:
Review of the Manuscript “Psychological distress affects memory function in breast cancer
survivors through inflammation levels”
I would like to thank for the opportunity to review the manuscript entitled “Psychological
distress affects memory function in breast cancer survivors through inflammation levels”, aimed
to “explore whether psychological distress affects cognitive function by influencing the level
of inflammation” in a sample of 104 breast cancer survivors. The study addressed an important
topic in the breast cancer context, investigating the complex relationship between psychological
and biological dimensions, and showed interesting results. However, there are several important
limitations and issues to note:
1. The authors conducted a mediation analysis in a study with a cross-sectional design, which
does not allow for establishing the temporal order between variables, leading to important
limitations regarding the causal direction of the relationships between the investigated variables
and possible biased results (please see: O’Laughlin et al., 2018; Schuler et al., 2024; Selig &
Preacher, 2009). Accordingly, the results should be interpreted with some caution and more
attention should be given to this limitation (which is only hinted at in the limitations section),
or the authors should consider using more appropriate analyses for a study with cross-sectional
design. In this form, the results obtained can only be considered preliminary, requiring more
investigation through longitudinal studies.
2. Moreover, related to the first point, the authors used causal language (e.g., “affect”;
“influence”) in various sections of the manuscript, which warrants careful consideration. It is
crucial that the authors exercise caution in the choice of language, aligning it more with the
study design employed.
3. The manuscript appears to report very similar data to a previously published study (Pang et
al., 2023) (in terms of the sample enrolled, the methodology used, and the variables examined),
which is neither mentioned in the introduction section, when state of the art is reported, nor
explicitly cited in the method section, considering that the research protocol is the same.
Moreover, the results of the present revised study are similar to those of the previous one, thus not
leading to a significant advancement in the state of the art regarding the topic under examination.
The only variable that was additionally examined within the present revised study is the level of
inflammatory markers in the blood. In this regard, the authors should make explicit whether other
scientific work has been conducted on the same sample of breast cancer survivors enrolled and,
if so, should explain the rationale for conducting secondary analyses similar to those performed
in the previous study.
Meanwhile, other minor limitations are highlighted per sections:
Abstract
1. Within the description of the parameters of inflammatory markers in the blood:
“(neutrophil-to- lymphocyte ratio (NLR), platelet-to-lymphocyte count (PLR), monocyte count-
to-lymphocyte count (MLR); granulocyte-to-lymphocyte ratio (GLR)); systemic immune-
inflammation index (SII))” the use of parentheses should be reformulated, as there seems to be
one more after GLR.
2. The sentence: “And to assess whether psychological distress predicts memory function
through cytokine/blood inflammation marker levels” appears to be unclear and disconnected
from the previous part. It is suggested that the authors consider rephrasing the sentence.
3. In the sentence: “The inflammatory markers of NLR (z=-2.585, p=0.010), GLR (z=-2.858,
p=0.004), and SII (z=-2.747, p=0.006) were higher than in the NPD group in the PD group.
0.006) were higher than the NPD group” it appears to be unclear in which of the two groups the
levels of inflammatory markers were higher, and the use of parentheses should be reviewed.
Introduction
1. Page 2, Line 9: The authors should specify what the term “D” refers to as it is not made
explicit previously in the text.
2. Page 3, Lines 11-14: The cited studies [10; 11; 12] do not report the results indicated by the
authors in the text. It is suggested that the authors refer to research that investigated the issues
discussed (e.g., Janelsins et al., 2017; Lange et al., 2019; Li et al., 2015; Vardy et al., 2019).
3. Page 3, Lines 29-33: When the authors introduce the relationship between psychological
distress and inflammatory markers, they refer to studies conducted in samples comprising of the
general population [17] or caregivers of cancer patients [18]. It is suggested that this relationship
be further discussed through recent studies conducted on samples of cancer patients, and in
particular breast cancer survivors, since this is the population examined by the authors (e.g.,
Blaes et al., 2023).
4. The aim of the study could be explained more clearly, suggesting the authors specify in more
detail the role of the level of inflammation variable and indicate the population examined.
5. The hypotheses of the study are not reported by the authors. If the study was intended to be
exploratory and there were no a priori hypotheses, this should be better specified.
Methods
1. Regarding the sample size, the authors did not report how the number of participants was
established. It is suggested to indicate whether a power analysis was conducted, or other methods
were used to establish the sample size required to perform the analyses.
2. In the description of the measurement instruments, it was not mentioned whether the
questionnaires used (MMSE; DT; PRMQ) have been validated in the language of the population
examined, and Cronbach’s alphas were not reported.
3. Page 5, Lines 15-16: The authors reported that “DT#5 scores were considered to be associated
with psychological distress.”. It is suggested to specify that based on this criterion the sample
was divided into PD group and NPD group since it is not explicitly stated.
4. Regarding statistical analysis, it appears unclear why the authors conducted correlation
analysis, considering that PD and NPD groups were already compared with the Mann-Whitney
U-test (Table 2). In addition, it is suggested the authors specify which variables are independent,
dependent, and mediators when describing the regression and mediation analyses.
Results
1. Page 8, Lines 1-3: “and statistically significant differences in PLR#z=-1.460, p=0.144# and
MLR#z=-0.211, p=0.833#differences were not statistically significant.”. The form in which the
results are reported appears unclear.
2. The titles of the tables reported are not described in detail, and in the notes (Table 3; Table 4;
Table 6) it is not specified what the use of bold is referring to.
3. In the paragraph "Analysis of intermediation effects," the authors report the tables not in
numbering order. It is suggested to firstly report the tables and results regarding the regression
analyses and lastly the mediation analyses, to make the presentation of the results clearer.
Moreover, it is suggested the authors specify how they arrived at including only the variables
IL-1# for the RM outcome and SII for the PM outcome in the mediation analyses by briefly
describing the results that emerged from the regression analyses, as it might appear unclear to
readers.
Discussion
1. In the initial part of the discussion, it is suggested the authors directly report the main results
of the study and relate them to the initial aim and hypothesis.
2. Page 13, Lines 4-8: In reporting the results, the authors refer initially to “BC patients” and
later to “BC survivors,” making the population under examination unclear.
Conclusion
1. The authors interestingly report that the results of the study may provide new ideas for
improving cognitive function in BC survivors. It might be worthwhile to discuss what the clinical
implications might then be for improving cognitive function in this population based on the
results of the study.
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