Malignant Phyllodes Tumor of the Breast: A Practice Review

Round 1

Reviewer 1 Report

The manuscript by Fede et al, “Malignant Phyllodes Tumor of the Breast: a practice review.”, provides an overview of a rare type of cancer with fibroepithelial origin. The authors succeed in summarizing the available clinical, pathological and therapeutic aspects of the disease and their study is a required addition to the field. The review is very informative and well written. 

I have the following comments:

1. English language is fine and I believe that very few sections need editing.
2. The authors should omit lines 62-65, because the section “Malignant PTs…elements;” is repeated in lines 65-68.
3. Figure 1 and Figure 2 have the exact same title. The authors should include a unique element in each Figure (such as magnification, specimen etc.), or they should consider combining the two Figures into one, multipanel Figure.

 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Based on several morphological characteristics and stroma overgrowth, the WHO Working Group classified PT as benign, borderline or malignant. Borderline or malignant tumors may recur locally, but only a low percentage of them metastasizes.

Many PTs have been analyzed by array-CGH: frequent chromosomal imbalances such as gains at 1q, 5p, 7 and 8 and losses at 6q, 9p, 10p and 13q were reported. 

Jones et al, Kuijper et al,  observed  an increasing rate of genetic defects from benign to malignant tumors .

Yeong et al  reported that mutations in PIK3CA, RB1, TP53, NF1, ERBB4 and EGFR might  promote progression of borderline to malignant phyllodes tumors.

Fortarezza et al in a recent paper reported that genomic profiling by a-CGH revealed a greater chromosomal instability in the borderline mass than in the malignant  giant phyllodes tumor.

 Therefore the authors in this review must point out these molecular aspects (expand the references), which can help clinicians in the definition of borderline tumors. 

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

Review

The study aims to describe an overview of phyllodes tumor addressing clinical, pathological and therapeutic aspects.

 

General observation of the manuscript:

Review the scores (especially the incorrect use of ; several times), uppercase and lowercase letters. Once acronyms are used, it is no longer necessary to repeat in full.

 

Abstract

The conclusions were not well developed according to the objectives of the study. What were the main clinical, pathological and treatment characteristics for these tumors that the authors would like to describe in the abstract?

“…multidisciplinary team consisting of surgeons, radiation and medical oncologist…” check some words that don't make sense.

 

Introduction

Line 31 – “most recent literature” – Did the authors establish search criteria?

Line 37 – “Lobular neoplasia, atypical ductal...” . Provide the reference after the end of the sentence.

Line 47 – “…characteristics; according to the WHO classification of breast tumors of 2019 those include tumor border, stromal cellularity, stromal cell atypia, stromal cell mitotic activity, presence of stromal overgrowth, and presence of malignant heterologous elements.” I suggest that the authors reformulate the connection between the two sentences. For example: For WHO, according to the latest classification for breast tumors (2019), phyllodes tumors are all those...”. In the way it is presented it is very confusing.

Figure 1 – Provide identification arrows for what is described in the legend.

Lines 62-66 – The texts are repeated.

Lines 62–76 – Observe the incorrect use of punctuation (;). In many situations the comma must be used.

Lines 75-76 – “Still, the clinical outcomes of primary breast sarcomas and malignant PTs seemingly tend to be comparable”. Which clinical outcomes? Authors need to better describe the information.

Figure 2 – Provide identification arrows for what is described in the legend.

Line 96 – “3. Phyllodes Tumors – Pathogenesis…” Remove this topic. The first paragraph is part of the previous topic, and the second of the genetic characteristics.

In the topic “Genetic Features”, the authors need to describe other important studies on the genetics of phyllodes tumors, especially those targeting somatic sequencing. For example:

1) Liu, SY., Joseph, N., Ravindranathan, A. et al. Genomic profiling of malignant phyllodes tumors reveals aberrations in FGFR1 and PI-3 kinase/RAS signaling pathways and provides insights into intratumoral heterogeneity. Mod Pathol 29, 1012–1027 (2016). https://doi.org/10.1038/modpathol.2016.97”

2) Kim JY, Yu JH, Nam SJ, et al. Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast. Transl Oncol. 2018;11(1):18-23. doi:10.1016/j.tranon.2017.10.002

3) Garcia-Dios, D., Levi, D., Shah, V. et al. MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours. Br J Cancer 118, 277–284 (2018). https://doi.org/10.1038/bjc.2017.450

4) Cani AK, Hovelson DH, McDaniel AS, et al. Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors. Mol Cancer Res. 2015;13(4):613-619. doi:10.1158/1541-7786.MCR-14-0578.

Lines 142-143 – Describe the BRCA1 and TP53 mutations (in brackets) of the study cited.

Line 156 – “Imaging findings” – It would be interesting for the authors to provide an image that illustrates the description of the first paragraph.

Line 227 – “In the largest prospective…” Start as paragraph.

Line 232 – “In a Japanese…” Start as paragraph.

Line 237 – “In view of the…” Start as paragraph.

Line 247 – “Given the conflicting…” Start as paragraph.

 

Conclusions

The conclusion is very vague and repeats the abstract. Authors need to better describe the findings of the review. What are the most important histopathological, genetic and treatment findings that need to be taken into account for phyllodes tumors? What are the perspectives that the authors see in relation to the studies described in the manuscript?

Comments for author File: Comments.pdf

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

none

Author Response

We are very grateful for the reviewer considerations.

Reviewer 3 Report

Suggestions and changes were made.

One last review, the references are not in the Journal´s standard. In particular, regarding publication dates, references are in a language other than English. In only one case, the authors are in capital letters. Please, check. 

Author Response

We have reviewed all references.