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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 5/2019

01-05-2019 | Breast Oncology

Local Recurrence of Benign, Borderline, and Malignant Phyllodes Tumors of the Breast: A Systematic Review and Meta-analysis

Authors: Yiwen Lu, MD, Yanbo Chen, MD, Liling Zhu, MD, Paul Cartwright, Erwei Song, MD, Lisa Jacobs, MD, Kai Chen, MD

Published in: Annals of Surgical Oncology | Issue 5/2019

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Abstract

Background

This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors (PTs). The study also assessed various risk factors for LR.

Methods

Electronic articles published between 1 January 1995 and 31 May 2018, were searched and critically appraised. The authors independently reviewed the abstracts and extracted data for LR rates and LR risk factors.

Results

The review incorporated 54 studies with 9234 individual cases. The pooled LR rates were 8% for benign, 13% for borderline, and 18% for malignant PTs. The risk of LR was significantly increased by borderline versus benign PTs (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.68–2.38) and malignant versus borderline PTs (OR 1.28; 95% CI 1.05–1.55). The significant risk factors for LR were mitoses, tumor border (infiltrating vs. pushing), stromal cellularity (moderate/severe vs. mild), stromal atypia (severe vs. mild/absent), stromal overgrowth (severe vs. mild/absent), and tumor necrosis (positive vs. negative). Age and tumor size were not associated with LR risk. The subgroup analysis showed that breast-conserving surgery versus mastectomy and positive versus negative surgical margins were significantly associated with an increased LR risk only in malignant PTs.

Conclusions

The risk of LR was significantly increased from benign to borderline to malignant PTs. Mitoses, tumor border, stromal cellularity, stromal atypia, stromal overgrowth, tumor necrosis, type of surgery, and surgical margin status may be risk factors for LR. Different management strategies could be considered for different PT grades.
Appendix
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Literature
1.
Krishnamurthy S, Ashfaq R, Shin HJ, et al. Distinction of phyllodes tumor from fibroadenoma: a reappraisal of an old problem. Cancer. 2000;90:342–9.CrossRefPubMed
2.
Rosen P, Overman H. Cystosarcoma phyllodes. In: Rosai J, Sobin L, editors. Atlas of tumor pathology. Tumors of the mammary gland. 3rd ed. Washington, DC: Armed Forces Institute of Pathology; 1993. pp. 107–14.
3.
Azzopardi JG, Ahmed A, Millis RR. Problems in breast pathology. Major Probl Pathol. 1979;11:1–466.
4.
Barrio AV, Clark BD, Goldberg JI, et al. Clinicopathologic features and long-term outcomes of 293 phyllodes tumors of the breast. Ann Surg Oncol. 2007;14:2961–70.CrossRefPubMed
5.
Kario K, Maeda S, Mizuno Y, et al. Phyllodes tumor of the breast: a clinicopathologic study of 34 cases. J Surg Oncol. 1990;45:46–51.CrossRefPubMed
6.
Ward RM, Evans HL. Cystosarcoma phyllodes: a clinicopathologic study of 26 cases. Cancer. 1986;58:2282–9.CrossRefPubMed
7.
Pietruszka M, Barnes L. Cystosarcoma phyllodes: a clinicopathologic analysis of 42 cases. Cancer. 1978;41:1974–83.CrossRefPubMed
8.
Co M, Chen C, Tsang JY, et al. Mammary phyllodes tumour: a 15-year multicentre clinical review. J Clin Pathol. 2018;71:493–7.CrossRefPubMed
9.
Matos AN, Neto J, Antonini, M, Ferraro O, Mancinelli B, Pereira A, Lopes R. Phyllodes tumors of the breast: a retrospective evaluation of cases from the hospital do servidor público estadual de São Paulo. Mastology. 2017;27:339–43.CrossRef
10.
Guillot E, Couturaud B, Reyal F, et al. Management of phyllodes breast tumors. Breast J. 2011;17:129–37.CrossRefPubMed
11.
Chaney AW, Pollack A, McNeese MD, et al. Primary treatment of cystosarcoma phyllodes of the breast. Cancer. 2000;89:1502–11.CrossRefPubMed
12.
Ganesh V, Drost L, Lee J, et al. A retrospective review of phyllodes tumours of the breast: a single-institution experience. Breast. 2018;38:52–7.CrossRefPubMed
13.
Jung C-W, Suh K-S, Lee J-S, et al. Mutation-free expression of c-Kit and PDGFRA in phyllodes tumors of the breast. J Breast Cancer. 2010;13:257.CrossRef
14.
Kim HM, Lee YK, Koo JS. Expression of CAF-related proteins is associated with histologic grade of breast phyllodes tumor. Dis Markers. 2016;2016:4218989.PubMedPubMedCentral
15.
Kim S, Kim JY, Kim DH, et al. Analysis of phyllodes tumor recurrence according to the histologic grade. Breast Cancer Res Treat. 2013;141:353–63.CrossRefPubMed
16.
Narayanakar RP, Gangaiah DM, Althaf S, et al. Cystosarcoma phyllodes: pathological enigma: a retrospective review of 162 cases. Indian J Cancer. 2015;52:365–8.CrossRefPubMed
17.
Wang K, Li Q, Shi R, et al. Increased CD105 expression is associated with disease progression in phyllodes tumors: a report of a borderline phyllodes tumor with lung metastases and a study of 54 phyllodes tumors. Ann Diagn Pathol. 2018;32:4–9.CrossRefPubMed
18.
Zhou ZR, Wang CC, Sun XJ, et al. Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients. Cancer Med. 2018;7:1030–42.CrossRefPubMedPubMedCentral
19.
Yom CK, Han W, Kim SW, et al. Reappraisal of conventional risk stratification for local recurrence based on clinical outcomes in 285 resected phyllodes tumors of the breast. Ann Surg Oncol. 2015;22:2912–8.CrossRefPubMed
20.
Spitaleri G, Toesca A, Botteri E, et al. Breast phyllodes tumor: a review of literature and a single-center retrospective series analysis. Crit Rev Oncol Hematol. 2013;88:427–36.CrossRefPubMed
21.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.CrossRefPubMed
22.
StataCorp. Stata statistical software: release 14. College Station, PA: StataCorp LP; 2015.
23.
Copenhagen: The Nordic Cochrane Centre. Review manager (RevMan). 5.1 ed. Oxford: The Cochrane Collaboration; 2011.
24.
Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. Oxford: The Cochrane Collaboration; 2011.
25.
26.
Borhani-Khomani K, Talman ML, Kroman N, et al. Risk of local recurrence of benign and borderline phyllodes tumors: a Danish population-based retrospective study. Ann Surg Oncol. 2016;23:1543–8.CrossRefPubMed
27.
Cheng SP, Chang YC, Liu TP, et al. Phyllodes tumor of the breast: the challenge persists. World J Surg. 2006;30:1414–21.CrossRefPubMed
28.
Chng TW, Gudi M, Lim SH, et al. Validation of the Singapore nomogram for outcome prediction in breast phyllodes tumours in a large patient cohort. J Clin Pathol. 2018;71:125–8.CrossRefPubMed
29.
Sotheran W, Domjan J, Jeffrey M, et al. Phyllodes tumours of the breast: a retrospective study from 1982 to 2000 of 50 cases in Portsmouth. Ann R Coll Surg Engl. 2005;87:339–44.CrossRefPubMedPubMedCentral
30.
Tan PH, Thike AA, Tan WJ, et al. Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol. 2012;65:69–76.CrossRefPubMed
31.
Choi N, Kim K, Shin KH, et al. Malignant and borderline phyllodes tumors of the breast: a multicenter study of 362 patients (KROG 16-08). Breast Cancer Res Treat. 2018;171:335–44.CrossRefPubMed
32.
Huang C-C, Liu T-P, Cheng S-P, et al. Surgical treatment of phyllodes tumor of the breast with the trend. J Exp Clin Med. 2014;6:161–5.CrossRef
33.
Karim RZ, Gerega SK, Yang YH, et al. Phyllodes tumours of the breast: a clinicopathological analysis of 65 cases from a single institution. Breast. 2009;18:165–70.CrossRefPubMed
34.
Moutte A, Chopin N, Faure C, et al. Surgical management of benign and borderline phyllodes tumors of the breast. Breast J. 2016;22:547–52.CrossRefPubMed
35.
Rodrigues MF, Truong PT, McKevitt EC, et al. Phyllodes tumors of the breast: the British Columbia Cancer Agency experience. Cancer Radiother. 2018;22:112–9.CrossRefPubMed
36.
Ruvalcaba-Limon E, Jimenez-Lopez J, Bautista-Pina V, et al. Phyllodes tumor of the breast: 307 treated cases, the largest Mexican experience at a single breast disease institution. Iran J Pathol. 2016;11:399–408.PubMedPubMedCentral
37.
Akrami M, Tahmasebi S, Talei A, et al. Clinical outcome of patients with breast phyllodes tumors: a retrospective analysis of 129 cases in Shiraz, Southern Iran. Middle East J Cancer. 2015;6:267–73.
38.
Amy L. A single-center experience and review of the literature: 64 cases of phyllodes tumors to better understand risk factors and disease management. Am Surg. 2014;81:309–15.
39.
Asoglu O, Ugurlu MM, Blanchard K, et al. Risk factors for recurrence and death after primary surgical treatment of malignant phyllodes tumors. Ann Surg Oncol. 2004;11:1011–7.CrossRefPubMed
40.
Belkacemi Y, Bousquet G, Marsiglia H, et al. Phyllodes tumor of the breast. Int J Radiat Oncol Biol Phys. 2008;70:492–500.CrossRefPubMed
41.
Bellezza G, Prosperi E, Del Sordo R, et al. IMP3 is strongly expressed in malignant phyllodes tumors of the breast: an immunohistochemical study. Int J Surg Pathol. 2016;24:37–42.CrossRefPubMed
42.
Ben Hassouna J, Damak T, Gamoudi A, et al. Phyllodes tumors of the breast: a case series of 106 patients. Am J Surg. 2006;192:141–7.CrossRefPubMed
43.
Chen WH, Cheng SP, Tzen CY, et al. Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases. J Surg Oncol. 2005;91:185–94.CrossRefPubMed
44.
Hassan MA, Sakr MA. Predictive factors of local recurrence and survival following primary surgical treatment of phyllodes tumors of the breast. J Egypt Nat. 2006;18:125–33.
45.
Ho SK, Thike AA, Cheok PY, et al. Phyllodes tumours of the breast: the role of CD34, vascular endothelial growth factor and beta-catenin in histological grading and clinical outcome. Histopathology. 2013;63:393–406.CrossRefPubMed
46.
Jang JH, Choi MY, Lee SK, et al. Clinicopathologic risk factors for the local recurrence of phyllodes tumors of the breast. Ann Surg Oncol. 2012;19:2612–7.CrossRefPubMed
47.
Kim G-E, Ki J-H, Lee KH, et al. Stromal matrix metalloproteinase-14 expression correlates with the grade and biological behavior of mammary phyllodes tumors. Appl Immunohistochem Mol Morphol. 2012;20:298–303.CrossRefPubMed
48.
Moo TA, Alabdulkareem H, Tam A, et al. Association between recurrence and re-excision for close and positive margins versus observation in patients with benign phyllodes tumors. Ann Surg Oncol. 2017;24:3088–92.CrossRefPubMed
49.
Ng CC, Tan J, Ong CK, et al. MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases. J Clin Pathol. 2015;68:685–91.CrossRefPubMed
50.
Niezabitowski A, Lackowska B, Rys J, et al. Prognostic evaluation of proliferative activity and DNA content in the phyllodes tumor of the breast: immunohistochemical and flow cytometric study of 118 cases. Breast Cancer Res Treat. 2001;65:77–85.CrossRefPubMed
51.
Ouyang Q, Li S, Tan C, et al. Benign phyllodes tumor of the breast diagnosed after ultrasound-guided vacuum-assisted biopsy: surgical excision or wait-and-watch? Ann Surg Oncol. 2016;23:1129–34.CrossRefPubMed
52.
Ramakant P, Chakravarthy S, Cherian JA, et al. Challenges in management of phyllodes tumors of the breast: a retrospective analysis of 150 patients. Indian J Cancer. 2013;50:345–8.CrossRefPubMed
53.
Reinfuss M, Mitus J, Duda K, et al. The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases. Cancer. 1996;77:910–16.CrossRefPubMed
54.
Renner K, Holzer B, Minai-Pour M, et al. Phyllodes tumours of the breast. Eur Surg. 2005;37:327–30.CrossRef
55.
Sevinc AI, Aksoy SO, Guray Durak M, et al. Is the extent of surgical resection important in patient outcome in benign and borderline phyllodes tumors of the breast? Turk J Med Sci. 2018;48:28–33.CrossRefPubMed
56.
Slodkowska E, Nofech-Mozes S, Xu B, et al. Fibroepithelial lesions of the breast: a comprehensive morphological and outcome analysis of a large series. Mod Pathol. 2018;31:1073–84.CrossRefPubMed
57.
Tremblay-LeMay R, Hogue JC, Provencher L, et al. How wide should margins be for phyllodes tumors of the breast? Breast J. 2017;23:315–22.CrossRefPubMed
58.
Tsang JY, Mendoza P, Putti TC, et al. E-cadherin expression in the epithelial components of mammary phyllodes tumors. Hum Pathol. 2012;43:2117–23.CrossRefPubMed
59.
60.
Wang F, Jia Y, Tong Z. Comparison of the clinical and prognostic features of primary breast sarcomas and malignant phyllodes tumor. Jpn J Clin Oncol. 2015;45:146–52.CrossRefPubMed
61.
Wang H, Wang X, Wang C-F. Comparison of clinical characteristics between benign borderline and malignant phyllodes tumors of the breast. Asian Pac J Cancer Prev. 2014;15:10791–5.CrossRefPubMed
62.
Wei J, Tan YT, Cai YC, et al. Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center. Chin J Cancer. 2014;33:492–500.PubMedPubMedCentral
63.
Xiao M, Zhu Q, Jiang Y, et al. Local recurrent phyllodes tumors of the breast: clinical and sonographic features. J Ultrasound Med. 2015;34:1631–8.CrossRefPubMed
64.
Yamada I, Iino Y, Yokoe T. Phyllodes tumors of the breast: a clinicopathological study of 118 cases. Surg Today. 1997;27:1137–43.CrossRef
65.
Zissis C, Apostolikas N, Konstantinidou A, et al. The extent of surgery and prognosis of patients with phyllodes tumor of the breast. Breast Cancer Res Treat. 1998;48:205–10.CrossRefPubMed
66.
Tan PH, Jayabaskar T, Chuah KL, et al. Phyllodes tumors of the breast: the role of pathologic parameters. Am J Clin Pathol. 2005;123:529–40.CrossRefPubMed
67.
Lakhani S, Ellis I, Schnitt S, et al. WHO classification of tumours of the breast. Geneva: World Health Organization; 2012.
68.
Lae M, Vincent-Salomon A, Savignoni A, et al. Phyllodes tumors of the breast segregate in two groups according to genetic criteria. Mod Pathol. 2007;20:435–44.CrossRefPubMed
69.
Tan J, Ong CK, Lim WK, et al. Genomic landscapes of breast fibroepithelial tumors. Nat Genet. 2015;47:1341–5.CrossRefPubMed
70.
Koh VCY, Thike AA, Nasir NDM, et al. Size and heterologous elements predict metastases in malignant phyllodes tumours of the breast. Virchows Arch. 2017;472:615–21.CrossRefPubMed
71.
Salvadori B, Cusumano F, Del Bo R, et al. Surgical treatment of phyllodes tumors of the breast. Cancer. 1989;63:2532–6.CrossRefPubMed
72.
de Roos WK, Kaye P, Dent DM. Factors leading to local recurrence or death after surgical resection of phyllodes tumours of the breast. Br J Surg. 1999;86:396–9.CrossRefPubMed
73.
Rageth CJ, O’Flynn EA, Comstock C, et al. First international consensus conference on lesions of uncertain malignant potential in the breast (B3 lesions). Breast Cancer Res Treat. 2016;159:203–13.CrossRefPubMedPubMedCentral
74.
Cowan ML, Argani P, Cimino-Mathews A. Benign and low-grade fibroepithelial neoplasms of the breast have low recurrence rate after positive surgical margins. Mod Pathol. 2016;29:259–65.CrossRefPubMed
75.
Park HL, Kwon SH, Chang SY, et al. Long-term follow-up result of benign phyllodes tumor of the breast diagnosed and excised by ultrasound-guided vacuum-assisted breast biopsy. J Breast Cancer. 2012;15:224–9.CrossRefPubMedPubMedCentral
76.
Zurrida S, Bartoli C, Galimberti V, et al. Which therapy for unexpected phyllode tumour of the breast? Eur J Cancer. 1992;28:654–7.CrossRefPubMed
77.
Zeng S, Zhang X, Yang D, et al. Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: a systematic review and meta-analysis. Mol Clin Oncol. 2015;3:663–71.CrossRefPubMedPubMedCentral
78.
Kim YJ, Kim K. Radiation therapy for malignant phyllodes tumor of the breast: an analysis of SEER data. Breast. 2017;32:26–32.CrossRefPubMed
79.
Blichert-Toft M, Hansen JP, Hansen OH, et al. Clinical course of cystosarcoma phyllodes related to histologic appearance. Surg Gynecol Obstet. 1975;140:929–32.PubMed
Metadata
Title
Local Recurrence of Benign, Borderline, and Malignant Phyllodes Tumors of the Breast: A Systematic Review and Meta-analysis
Authors
Yiwen Lu, MD
Yanbo Chen, MD
Liling Zhu, MD
Paul Cartwright
Erwei Song, MD
Lisa Jacobs, MD
Kai Chen, MD
Publication date
01-05-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 5/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-07134-5

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