Impact of Pregnancy on Breast Cancer Features and Prognosis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The study aims to reveal whether simultaneous or sequential pregnancy with breast cancer changes the patient's hope for survival. The thesis examines a set of almost three hundred breast cancer patients under the age of 45 between 1995 and 2019 in two Italian institutions. The aims and methodology of the study are very well described and the outputs are statistically processed. The study's results resonate with other available data.

I see the following problems in the presented work:

1. The patients are collected over a period of 25 years, when the treatment options changed considerably, given that this applies to all studied groups, this should not be a problem, however, there were only 40 patients with PABC in the study, so it could mean a certain bias.

2. It is known that patients with PABC have a different prognosis even in this subgroup, patients diagnosed during pregnancy have better survival than patients diagnosed during breastfeeding, here, for understandable reasons of small numbers, both cases are evaluated together.

3. In the analyses, mainly clinical and clinicopathological information about patients are evaluated, without the results of genetic predispositions and, of course, also molecular biological parameters of tumors, especially due to the long interval of collection of patients. Nevertheless, it would be interesting to evaluate the available parameters in some patients treated recently. An obstacle will probably be the small number of patients in the PABC group.

4. In the course of 25 years, the treatment approach to pregnant women who are being treated for breast cancer has also fundamentally changed. Systemic treatment is administered from the second trimester, patients do not needlessly undergo mastectomy, neoadjuvant treatment with taxol weekly is administered until delivery without the need to skip it, as this treatment does not threaten the patient with neutropenia and a greater number of patients give birth spontaneously.

5. Due to the increasing number of patients with PABC, most likely due to the postponement of the first pregnancy until a later age, there are considerations about the possibility of screening pregnant women.

6. In recent years, we have also faced a completely new situation, namely the pregnancy of patients with metastatic breast cancer, especially in connection with the longer survival of these patients and the expansion of access to IVF techniques.

Despite the mentioned weaknesses, the work is of high quality, contains data from real practice and confirms the previously known fact that pregnancy in itself affects the prognosis of premenopausal patients minimally, the factors that worsen treatment outcomes are mainly the unfavorable clinical and histological profile of the tumor during pregnancy and during breastfeeding and delay or modification of treatment due to pregnancy.

Author Response

Dear Reviewer,

Firstly, I would like to thank you for your consideration. We have carefully considered your comments and worked on a revision of the manuscript, based on given observations. We answered to all the issues improving the quality of the paper, please see the attachement. All variations have been highlighted in the text. 

Do not hesitate to contact me for anything you may need. We will send you any further explanation, should it be needed. We look forward to receiving your opinion about our revised manuscript, and we are open to any other revisions might be suggested.

With kind regards,

Valentina Bounous on behalf of all authors

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have submitted a well written manuscript regarding a retrospective analysis comparing nulliparous young women with breast cancer and women with PABC. The authors are discussing the definition of PABC they used but only state that they are following the definitions of other authors. Please discuss in introduction and discussion why you did nit follow the definitions of the ESMO practice guideline published by Sybitte Loibl et al. in Ann Onc in October 2023. Of course it is ok to use another definiton but please explain why you did not these proposals. Furthermore I would recommend to discuss the validity of the dataset. If ER and grade have no influence on prognosis at all, what does that say about other prognostic parameters in the study? The limitations are mentioned but this issue needs to be discussed too. 

Author Response

Dear Reviewer,

Firstly, I would like to thank you for your consideration. We have carefully considered your comments and worked on a revision of the manuscript, based on given observations. We answered to all the issues improving the quality of the paper, please see the attachement. All variations have been highlighted in the text. 

Do not hesitate to contact me for anything you may need. We will send you any further explanation, should it be needed. We look forward to receiving your opinion about our revised manuscript, and we are open to any other revisions might be suggested.

With kind regards,

Valentina Bounous on behalf of all authors

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript by Bounous et al present an important study toe address the impact of pregnancy on breast cancer characteristics and prognosis. Its design, analysis, and findings are comprehensive and address a critical gap in current research. The investigation into the effects of pregnancy on breast cancer, a relatively underexplored area, is timely given the trend towards later pregnancies and the consequent rise in pregnancy-associated breast cancer (PABC). The inclusion of 282 young breast cancer patients treated over a 24-year span provides a solid dataset for analysis, and the categorization into three groups based on pregnancy status facilitates a nuanced understanding of pregnancy's influence on breast cancer.

However, the manuscript could be enhanced in several areas:

1.      Given the significant variability in the definition of PABC across the literature, the authors' choice of definition should be more thoroughly justified. Acknowledging this variability and providing a strong rationale for their choice would solidify the study's foundation.

2.       An in-depth analysis of subgroups, particularly distinguishing between breast cancer diagnosed during pregnancy and in the post-partum period, could yield valuable insights into their distinct biological and prognostic characteristics.

3.       The finding that pregnancy is not an independent adverse prognostic factor for breast cancer disease-free survival (DFS) is noteworthy. The discussion would benefit from a more detailed comparison with existing studies, especially those with contrasting results, to contextualize this finding better.

4.       Exploring the biological mechanisms behind the observed lack of significant difference in DFS between PABC and non-PABC patients could provide deeper insight into the complex relationship between pregnancy and breast cancer biology.

5.       The study's limitation, due to the relatively small sample size of the PABC population, should be acknowledged. Expanding the discussion to consider potential biases, such as selection bias and information bias, and their impact on the findings would enhance the manuscript's credibility.

In conclusion, the manuscript offers valuable insights into the impact of pregnancy on breast cancer features and prognosis. Addressing the aforementioned points could further enhance the manuscript's quality and contribute to a more comprehensive understanding of this important area.

Author Response

Dear Reviewer,

Firstly, I would like to thank you for your consideration. We have carefully considered your comments and worked on a revision of the manuscript, based on given observations. We answered to all the issues improving the quality of the paper, please see the attachement. All variations have been highlighted in the text. 

Do not hesitate to contact me for anything you may need. We will send you any further explanation, should it be needed. We look forward to receiving your opinion about our revised manuscript, and we are open to any other revisions might be suggested.

With kind regards,

Valentina Bounous on behalf of all authors

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thanks for editing the content of the article. The text is significantly improved.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed all issues accordingly. I have no further comments.