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Systemic treatment in advanced phyllodes tumor of the breast: a multi-institutional European retrospective case-series analyses

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Abstract

Background

We aimed at investigating outcome of systemic treatments in advanced breast PT.

Methods

All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed.

Results

56 female patients were identified. Median age was 52 (range of 25–76) years. Patients received a median number of 2 systemic treatments (range of 1–4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5–9.1) months with AI; 3.2 (IQR 2.2–5.0) months with anthracycline alone; 3.4 (IQR 1.4–6.7) months with HD-IFX; 2.1 (IQR 1.4–5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7–6.6) months with trabectedin; 3.4 (IQR 3.1–3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6–66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6–39.6) months.

Conclusion

In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

PT:

Breast phyllodes tumor

HD-IFX:

High-dose ifosfamide

TKI:

Tyrosine-kinase inhibitors

CTCAE:

Cancer Institute Common Toxicity Criteria

RECIST:

Response Evaluation Criteria in Solid Tumors

ORR:

Overall response rate

PFS:

Progression-free survival

OS:

Overall survival

AI:

Anthracycline plus ifosfamide

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

References

  1. Tan PH, TSe G, Koo JS et al (2019) Fibroepithelial tumours. WHO classification of tumours of the breast. Lyon 172–176

  2. Zhang Y, Kleer CG (2016) Phyllodes tumor of the breast: histopathologic features, differential diagnosis, and molecular/genetic updates. Arch Pathol Lab Med 140(7):665–671

    Article  Google Scholar 

  3. Telli ML, Horst KC, Guardino AE et al (2007) Phyllodes tumors of the breast: natural history, diagnosis, and treatment. J Natl Compr Canc Netw 5(3):324–330

    Article  Google Scholar 

  4. Spitaleri G, Toesca A, Botteri E et al (2013) Breast phyllodes tumor: a review of literature and a single center retrospective series analysis. Crit Rev Oncol Hematol 88(2):427–436

    Article  Google Scholar 

  5. Neron M, Sajous C, Thezenas S et al (2020) French Sarcoma Group (GSF-GETO). Impact of metastasis surgery and alkylating-agent-based chemotherapy on outcomes of metastatic malignant phyllodes tumors: a multicenter retrospective study. Ann Surg Oncol. 27(5):1693–1699

    Article  Google Scholar 

  6. Mituś JW, Blecharz P, Walasek T et al (2016) Treatment of patients with distant metastases from phyllodes tumor of the breast. World J Surg 40(2):323–328

    Article  Google Scholar 

  7. Ramakant P, Therese MM et al (2015) Metastatic malignant phyllodes tumor of the breast: an aggressive disease-analysis of 7 cases. Indian J Surg Oncol. 6(4):363–9

    Article  Google Scholar 

  8. Parkes A, Wang WL, Patel S et al (2021) Outcomes of systemic therapy in metastatic phyllodes tumor of the breast. Breast Cancer Res Treat 186(3):871–882

    Article  CAS  Google Scholar 

  9. CTEP.Cancer.gov [homepage on the internet]. Bethesda: NCI; [updated 2017 Nov 27]. http://ctep.cancer.gov/protocol/Development/electronic_applications/ctc.htm#ctc_50.

  10. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247

    Article  CAS  Google Scholar 

  11. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53(282):457–481

    Article  Google Scholar 

  12. Judson I, Verweij J, Gelderblom H et al (2014) European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol 15(4):415–23

    Article  CAS  Google Scholar 

  13. Grignani G, D’Ambrosio L, Pignochino Y et al (2018) Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group. Lancet Oncol 19(10):1360–1371

    Article  CAS  Google Scholar 

  14. Park IH, Kwon Y, Kim EA et al (2009) Major response to sunitinib (Sutene) in metastatic malignant phyllodes tumor of breast. Invest New Drugs 27(4):387–388

    Article  Google Scholar 

  15. Casali PG, Abecassis N, Aro HT et al (2018) ESMO Guidelines Committee and EURACAN. Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29:268–269

    Article  Google Scholar 

  16. Cani AK, Hovelson DH, McDaniel AS et al (2015) Next-gen sequencing exposes frequent MED12 mutations and actionable therapeutic targets in phyllodes tumors. Mol Cancer Res 13(4):613–619

    Article  CAS  Google Scholar 

  17. Liu SY, Joseph NM, Ravindranathan A et al (2016) 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(9):1012–1027

    Article  CAS  Google Scholar 

  18. Piscuoglio S, Geyer FC, Burke KA et al (2016) Massively parallel sequencing analysis of synchronous fibroepithelial lesions supports the concept of progression from fibroadenoma to phyllodes tumor. NPJ Breast Cancer 2:16035

    Article  Google Scholar 

  19. Nozad S, Sheehan CE, Gay LM et al (2017) Comprehensive genomic profiling of malignant phyllodes tumors of the breast. Breast Cancer Res Treat 162(3):597–602

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are thankful to our patients who participated in this research to allow us to study a rare disease.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    E. Palassini, F. Bini, S. Provenzano & P. G. Casali

  2. Department of Ambulatory Cancer Care, Sarcoma Group, Gustave Roussy, Villejuif, France

    O. Mir, I. Gataa & A. Le Cesne

  3. Division of Medical Oncology, Candiolo Cancer Institute, FPO – IRCCS, Candiolo, TO, Italy

    G. Grignani

  4. Department of Medical Oncology, Campus Biomedico University, Rome, Italy

    B. Vincenzi

  5. Department of Medical Oncology, LUMC - Leiden University Medical Center, Leiden, Netherlands

    H. Gelderblom

  6. Hospital Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

    A. Sebio

  7. Vall d’Hebron University Hospital, Barcelona, Spain

    C. Valverde

  8. Department of Medical Oncology, Ospedale “Santo Stefano”, Prato, Italy

    G. G. Baldi

  9. Department of Oncology, Oncology 1 Unit, Istituto Oncologico Veneto - IOV, IRCCS, Padua, Italy

    A. Brunello

  10. Department of Oncology, Presidio “S. Maria della Misericordia” di Udine, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy

    G. G. Cardellino

  11. Department of Oncology and Hematology, Humanitas Cancer Center Rozzano, Rozzano, Milan, Italy

    A. Marrari

  12. Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy

    G. Badalamenti

  13. Fundación Jiménez Díaz University Hospital, Madrid, Spain

    J. Martin-Broto

  14. Sarcomas and Rare Tumors Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

    V. Ferraresi

  15. Department of Oncology, Fondazione Poliambulanza, Brescia, Italy

    M. Libertini

  16. Department of Oncology, Azienda Ospedaliera di Cosenza, Cosenza, Italy

    S. Turano

  17. Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    P. Collini

  18. Department of Pathology, Azienda Ospedaliera Università Padova, Padua, Italy

    A. P. Dei Tos

  19. Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    M. Gennaro

  20. Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    S. Lo Vullo & L. Mariani

Authors
  1. E. Palassini
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  2. O. Mir
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  3. G. Grignani
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  4. B. Vincenzi
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  5. H. Gelderblom
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  6. A. Sebio
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  7. C. Valverde
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  8. G. G. Baldi
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  9. A. Brunello
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  10. G. G. Cardellino
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  11. A. Marrari
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  12. G. Badalamenti
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  13. J. Martin-Broto
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  14. V. Ferraresi
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  15. M. Libertini
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  16. S. Turano
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  17. I. Gataa
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  18. P. Collini
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  19. A. P. Dei Tos
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  20. M. Gennaro
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  21. F. Bini
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  22. S. Provenzano
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  23. S. Lo Vullo
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  24. L. Mariani
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  25. A. Le Cesne
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  26. P. G. Casali
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Contributions

Conceptualization, EP and PGC; methodology, EP, PGC, LM; software, SLV; validation, EP and PGC; formal analysis, SLV, and LM; investigation, all.; resources, all.; data curation, EP, and SLV; writing original draft preparation, EP, and PGC; writing review and editing, all.; visualization, FB, and EP; supervision, PGC All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to E. Palassini.

Ethics declarations

Conflict of interest

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. EP and SP reports institutional financial interest in Advenchen, Amgen-Dompe, Bayer, Epizyme, Eli Lilly, Daiichi-Sankyo, GlaxoSmithKline, Karyopharm, Novartis, Pfizer, PharmaMar, and SpringWorks Therapeutics. OM reports Advisory Board for Bayer, Blueprint Medicines, MSD, Pfizer, Invited Speaker for BMS, Eli-Lilly, Roche, Servier and Institutional, Financial interest as Local PI for Bayer, Blueprint Medicines, Eli-Lilly, Epizyme. AS reports advisory role for Pharmamar and also travel and congress assistance, research, teaching from Pharmamar, teaching, travel and congress assistance from Lilly, Eisai and travel and congress assistance from Merc, Amgen, Sanofi. CV reports Advisory Board for Bayer, Boehringer Ingelheim, GSK, Lilly, Mundipharma, Phar-maMar; Invited Speaker from Roche; Institutional, Financial interest as Local PI from Adap-timmune, Karyopharm, Lilly. GGB reports Honoraria from Eli Lilly, Eisai, PharmaMar and MSD; travel grants from PharmaMar, Pfizer and Eli Lilly; advisory board from Eli Lilly and Glaxo Smith Kline. AB reports Consultancy/Advisory board for Eli Lilly, Eisai, Glaxo Smith Kline; Speakers' fees from PharmaMar; Travel grants from PharmaMar. JMB reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from PharmaMar, Lilly, Bayer, Eisai, Daichii; grants or contracts from Pharmamar, Novartis, Eisai, IMMIX Biopharma; payment for expert testimony from Phar-maMar, Lilly, Bayer, Eisai, Daichii; participation on a Data Safety Monitoring Board or Advisory Board for Roche, Lilly, PharmaMar; Leadership or fiduciary role in board, society, committee or advocacy group for Daiichi Sankyo, Karyopharm, Celgene, Pfizer, BMS, Blueprint, Deciphera, Nektar, Forma, Amgen, Lixte, GEIS, CTOS, ESMO, SELNET. PGC reports honoraria and consultancy or advisory fees from Bayer, Deciphera, Eisai, Eli Lilly, and Pfizer outside the submitted work and institutional financial interest in Advenchen Labora-tories, Amgen Dompe, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi-Sankyo, De-ciphera, Eisai, Eli Lilly, Epizyme, GlaxoSmithKline, Karyopharm, Novartis, Pfizer, and Pharma-Mar. Other authors: no competing interests to declare.

Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Fondazione IRCCS Istituto Nazionale Tumori di Milano (protocol code 255/20, date 05/11/2020).

Informed consent

Informed consent was obtained from all subjects involved in the study.

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Palassini, E., Mir, O., Grignani, G. et al. Systemic treatment in advanced phyllodes tumor of the breast: a multi-institutional European retrospective case-series analyses. Breast Cancer Res Treat 192, 603–610 (2022). https://doi.org/10.1007/s10549-022-06524-4

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  • DOI: https://doi.org/10.1007/s10549-022-06524-4

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