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

  • Yiwen Lu
  • Yanbo Chen
  • Liling Zhu
  • Paul Cartwright
  • Erwei Song
  • Lisa Jacobs
  • Kai Chen
Breast Oncology

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.

Notes

Acknowledgment

This study was supported by grants from the National Key Research and Development Program of China (2017YFC1309100), the National Natural Science Foundation of China (Grant Nos. 81402201, 81372817), the National Natural Science Foundation of Guangdong Province (Grant Nos. 2014A030310070, 2017A030313705), the China Postdoctoral Science Foundation (Grant No. 2018M633249), and Grant [2013]z163 from the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology. We are grateful to Yaping Yang for statistical advice. This work was supported by the Yat-sen Scholarship of Young Scientist of Sun Yat-sen Memorial Hospital.

Disclosure

The authors declare that they have no conflict of interest.

Supplementary material

10434_2018_7134_MOESM1_ESM.tif (63 kb)
Supplemental Fig. S1 Flow diagram of the selected studies (TIFF 62 kb)
10434_2018_7134_MOESM2_ESM.tif (19.1 mb)
Supplemental Fig. S2 a Forest plot of the local recurrence (LR) rates for overall phyllodes tumors (PTs). The effect size (ES) represented the calculated LR rate of PTs in each study after combining of all studies. b Forest plot of the LR rate for the benign PTs. The ES represented the calculated LR rate for the benign PTs in each study after combining of all studies. c Forest plot of the LR rates for the borderline PTs. The ES represented the estimated LR rate for the borderline PTs. d Forest plot of the LR rates for the malignant PTs. The ES represented the estimated LR rate for the malignant PTs (TIFF 19537 kb)
10434_2018_7134_MOESM3_ESM.tif (12.9 mb)
Supplemental Fig. S3 a Forest plot showing the pooled hazard ratio (HR) of local recurrence (LR) by age (≥ 40 vs. < 40 years). b Forest plot showing the pooled HR of LR by tumor size (> 5 vs. ≤ 5 cm). c Forest plot showing the pooled HR of LR by surgical margin (positive vs. negative). All included studies defined a positive margin as a tumor present on the surgical margin (TIFF 13190 kb)
10434_2018_7134_MOESM4_ESM.tif (12.6 mb)
Supplemental Fig. S4 a Forest plot showing the pooled odds ratios (ORs) of local recurrence (LR) by surgery type (breast-conserving surgery vs. mastectomy) stratified by the phyllodes tumor (PT) grade. b Forest plot showing the pooled ORs of LR by surgical margin (positive vs. negative) stratified by the PT grade. The surgical margin width in each study was marked in the footnote (Fig. 2). The LR rate stratified by surgery (breast-conserving surgery (BCS) vs. mastectomy) and grade reported by Narayanakar et al.16 was conflicting, so the study was not included in this analysis (TIFF 12944 kb)
10434_2018_7134_MOESM5_ESM.tif (12.5 mb)
Supplemental Fig. S5 Forest plot showing the pooled odds ratios (ORs) of local recurrence (LR) by mitoses (≥ 10 vs. < 10/10 HPF), tumor border (infiltrative vs. pushing), stromal cellularity (moderate/severe vs. mild), stromal atypia (severe vs. absent/mild), stromal overgrowth (severe vs. absent/mild), and tumor necrosis (positive vs. negative). #In Spitaleri et al.,20 three events (20 altogether) were not LR. One case had recurrence in the breast and axilla, and two cases had distant metastases (TIFF 12807 kb)
10434_2018_7134_MOESM6_ESM.tif (13.6 mb)
Supplemental Fig. S6 Funnel plot to assess the publication bias of the included studies (TIFF 13893 kb)
10434_2018_7134_MOESM7_ESM.tif (6.8 mb)
Supplemental Fig. S7 a Forest plot of the upgrade rate for benign phyllodes tumors (PTs). b Forest plot of the upgrade rate for borderline PTs. The effect size (ES) represented the calculated upgrade rate of local recurrent PTs in each study after combining of all studies (TIFF 6914 kb)
10434_2018_7134_MOESM8_ESM.docx (55 kb)
Supplementary material 8 (DOCX 49 kb)

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© Society of Surgical Oncology 2019

Authors and Affiliations

  1. 1.Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  2. 2.Breast Tumor Center, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
  3. 3.Departments of SurgeryJohns Hopkins Medical InstitutionsBaltimoreUSA

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