Abstract
Background
Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs).
Patients and Methods
A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate.
Results
51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31–80 months]. Median OS was 11.5 months (95% CI 7.5–18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27–6.19; p = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14–0.78; p = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone (p = 0.049).
Conclusions
The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.
Similar content being viewed by others
References
World Health Organization. WHO Classification of Tumours of the Breast, Fourth Edition. http://apps.who.int/bookorders/anglais/detart1.jsp?codlan=1&codcol=70&codcch=4004. Published 2012. Accessed March 25, 2017.
Onkendi EO, Jimenez RE, Spears GM, Harmsen WS, Ballman KV, Hieken TJ. Surgical treatment of borderline and malignant phyllodes tumors: the effect of the extent of resection and tumor characteristics on patient outcome. Ann Surg Oncol. 2014;21(10):3304–9. https://doi.org/10.1245/s10434-014-3909-x
Tan BY, Acs G, Apple SK, et al. Phyllodes tumours of the breast: a consensus review. Histopathology. 2016;68(1):5–21. https://doi.org/10.1111/his.12876
de Foucher T, Roussel H, Hivelin M, et al. Atypical distant metastasis of breast malignant phyllodes tumors: a case report and literature review. Case Rep Obstet Gynecol. 2017;2017:8963013. https://doi.org/10.1155/2017/8963013
Mituś JW, Blecharz P, Walasek T, Reinfuss M, Jakubowicz J, Kulpa J. Treatment of patients with distant metastases from phyllodes tumor of the breast. World J Surg. 2016;40(2):323–8. https://doi.org/10.1007/s00268-015-3262-7
Ramakant P, Selvamani null, Therese MM, Paul MJ. Metastatic malignant phyllodes tumor of the breast: an aggressive disease-analysis of 7 cases. Indian J Surg Oncol. 2015;6(4):363–9. https://doi.org/10.1007/s13193-015-0397-9
Shan J, Zhang S, Wang Z, Fu Y, Li L, Wang X. Breast malignant phyllodes tumor with rare pelvic metastases and long-term overall survival: a case report and literature review. Medicine (Baltimore). 2016;95(38):e4942. https://doi.org/10.1097/md.0000000000004942
Cariboni U, De Sanctis R, Giaretta M, et al. Survival outcome and prognostic factors after pulmonary metastasectomy in sarcoma patients: a 18-year experience at a single high-volume referral center. Am J Clin Oncol. 2018. https://doi.org/10.1097/coc.0000000000000476
Casali PG, Abecassis N, Bauer S, et al. Soft tissue and visceral sarcomas: ESMO-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2018. https://doi.org/10.1093/annonc/mdy096
Judson I, Verweij J, Gelderblom H, et al. 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. 2014;15(4):415–23. https://doi.org/10.1016/s1470-2045(14)70063-4
Bedi M, King DM, Charlson J, et al. Multimodality management of metastatic patients with soft tissue sarcomas may prolong survival. Am J Clin Oncol. 2014;37(3):272–7. https://doi.org/10.1097/coc.0b013e318277d7e5
Chudgar NP, Brennan MF, Munhoz RR, et al. Pulmonary metastasectomy with therapeutic intent for soft-tissue sarcoma. J Thorac Cardiovasc Surg. 2017;154(1):319–30.e1. https://doi.org/10.1016/j.jtcvs.2017.02.061
Smolle MA, van Praag VM, Posch F, et al. Surgery for metachronous metastasis of soft tissue sarcoma—a magnitude of benefit analysis using propensity score methods. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2018. https://doi.org/10.1016/j.ejso.2018.06.019
Krishnan CK, Kim H-S, Park JW, Han I. Outcome after surgery for extremity soft tissue sarcoma in patients presenting with metastasis at diagnosis. Am J Clin Oncol. 2018;41(7):681–6. https://doi.org/10.1097/coc.0000000000000346
Hawkins RE, Schofield JB, Wiltshaw E, Fisher C, McKinna JA. Ifosfamide is an active drug for chemotherapy of metastatic cystosarcoma phyllodes. Cancer. 1992;69(9):2271–5.
Burton GV, Hart LL, Leight GS, Iglehart JD, McCarty KS, Cox EB. Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy. Cancer. 1989;63(11):2088–92.
Gatalica Z, Vranic S, Ghazalpour A, et al. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast. Oncotarget. 2016;7(2):1707–16. https://doi.org/10.18632/oncotarget.6421
Nozad S, Sheehan CE, Gay LM, et al. Comprehensive genomic profiling of malignant phyllodes tumors of the breast. Breast Cancer Res Treat. 2017;162(3):597–602. https://doi.org/10.1007/s10549-017-4156-1
Confavreux C, Lurkin A, Mitton N, et al. Sarcomas and malignant phyllodes tumours of the breast—a retrospective study. Eur J Cancer Oxf Engl 1990. 2006;42(16):2715–21. https://doi.org/10.1016/j.ejca.2006.05.040.
Acknowledgment
The authors are grateful to all patients and their families. They also thank Dr. Hélène de Forges for substantive editing, Dr. Francoise Ducimetière for data management, and Dr. Sebastien Carrere, Dr. Carmen Llacer, Dr. Aurélie Maran-Gonzalez, Dr. Didier Cupissol, Dr. Alexandre de Nonneville, and Dr. Maud Toulmonde for patient inclusions.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Disclosures
The authors have no conflicts of interest to declare for this study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Neron, M., Sajous, C., Thezenas, S. et al. Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study. Ann Surg Oncol 27, 1693–1699 (2020). https://doi.org/10.1245/s10434-019-08097-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-019-08097-x