Title: Survival benefits of postoperative radiotherapy in patients with cT1-2N1M0 breast cancer
after neoadjuvant chemotherapy: A SEER-Based population study
Version: 0 Date: 03 Aug 2023
Reviewer's report:
In the current manuscript, the authors examine the effect of adjuvant radiation therapy (RT) on
overall survival (OS) and breast cancer-specific survival (CSS) in patients with CT1-2N1M0
breast cancer who receive neoadjuvant chemotherapy using the SEER database.
They show that RT improved OS but not CSS, even after propensity score matching (PSM)
of the two populations for surgical method. Although interesting, this study, similarly to
other database-derived retrospective studies, is severely biased, rendering overall survival a
meaningless endpoint. Another concern is the fact that RT had an effect on OS but not on CSS,
even after PSM.
The authors have included clinically meaningless variables in their analysis such as marital status
and did not included important variables such as comorbidity score which could have major
effect on adjuvant RT decisions.
Lastly, the manuscript is written in a very disorganized way which would make it very hard on
the reader to understand what the authors are trying to show.
I also include the following questions/suggestions:
1. The methods section in the abstract should include more details on the inclusion and exclusion
criteria that were used to identify the study cohort such as: age, years of diagnosis, staging and
treatments. The number of patients that were included should be mentioned in the results section.
2.  I do not think the term radical mastectomy is correct. I understand the authors aimed to
compare between breast conserving surgery and mastectomy. Is that the term used in the SEER
database for mastectomy?
3. Why did the authors include marital status as a variable?
4. The sentence in the results section “Nevertheless, patients who received radiotherapy had a
higher 10-year CSS rate, with a rate of 81.4% (95% CI: 77.1-85.9%) in the radiotherapy group
and 76.2% (95% CI: 69.2-83.8%) in the no-radiotherapy group” should be rephrased so it is
clearer.
5. In the results section (survival after PSM) the authors mention several characteristics in their
subgroup analysis that should be better clarified such as right-sided should be rephrased to right-
sided cancers, what does non-inner/outer quadrant mean? breast quadrants are named either
inner/outer and either upper/lower, does intermediate differentiation refer to intermediate grade?
6. In the discussion part the authors mention that “the risk of death due to cardiac toxicity after
radiation is higher for left breast cancer patients than for right breast cancer patients”. This
should be supported with a reference.
7. Both in the introduction and discussion sections, the authors do not include relevant references
consistently when citing studies and data.
8. In the discussion the authors mention that “Overall, SLNB negativity is still an important
guiding factor for avoiding axillary radiation therapy and ALND after NAC in cN1 breast
cancer patients”. this is not entirely true as currently according to guidelines, SLNB negativity
following NAC can only help avoid ALND in specific cases but not radiation therapy which is
guided by pre-treatment lymph node status.
9. Figures legends should include abbreviations of synonyms without referring to the manuscript
itself.
10. Figure 1 is very disorganized and unclear – in the inclusion criteria box the T and M stages
are mentioned but not the N stage, the order in which the inclusion criteria are presented does
not make sense. Additionally, no radiation therapy is not an exclusion criteria as the authors
compare between patients that receive and did not receive radiation therapy.
11. In the discussion, it would be nice to add a paragraph on current clinical trials which are
underway to assess the exact question the authors are looking at retrospectively.
12. In table 1 – what does SURFS means? It is also not mentioned among the abbreviations.