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Width of margins in phyllodes tumors of the breast: the controversy drags on?—a systematic review and meta-analysis

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Abstract

Purpose

Phyllodes tumors (PT) of the breast are rare fibroepithelial neoplasms. Information is controversial in the literature regarding to the optimal surgical management. Most studies suggested margins of at least 10 mm while some recent studies suggested narrower margins without an increased risk of local recurrences (LR) and distant metastases (DM). The objective of this systematic review was to identify and compare studies that assessed these different practices.

Methods

A systematic review was performed through five databases up to April 2019. Studies exploring the association between the width of margins, subtypes of PT, and the LR and DM rates were considered for inclusion. A statistical model for analyzing sparse data and rare events was used.

Results

Thirteen studies met eligibility criteria and were selected. Considering a threshold of 10 mm (margins < 10 vs margins ≥ 10 mm), the 5-year incidence rate of LR was estimated to be 5.22 vs. 3.63 (diff. −1.59) per 100 person-years for benign PT, 9.60 vs. 7.33 (diff. −2.27) for borderline PT, and 28.58 vs. 21.84 (diff. −6.74) for malignant PT. For DM, it was estimated to be 0.88 vs. 0.86 (diff. −0.02) for benign PT, 1.61 vs. 1.74 (diff. 0.13) for borderline PT, and 4.80 vs 5.18 (diff. 0.38) for malignant PT. The data for a threshold of 1 mm were not sufficient to draw any conclusions.

Conclusion

Irrespective of tumor grade, we found that DM was a rarer event than LR. Malignant PT had the highest incidence rate of LR and DM. This meta-analysis found a clear association between width of margins and LR rates. Whatever the tumor grade, surgical margins ≥ 10 mm guaranteed a lower risk of LR than margins < 10 mm. On the other hand, the width of margin did not influence the apparition of DM.

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Acknowledgements

This work was supported by the department of gynecology, obstetrics and medical genetics, University Hospital of Lausanne, Switzerland.

Funding

This meta-analysis was funded by the department of gynecology, obstetrics and medical genetics, University Hospital of Lausanne, Switzerland.

Author information

Authors and Affiliations

  1. Division of Mammo-Pelvic Surgery, Department of Gynecology, Obstetrics and Medical Genetics. University Hospital of Lausanne, Av. Pierre-Decker 2, CH-1011, Lausanne, Switzerland

    Arnaud Toussaint & Patrice Mathevet

  2. Division of Mammo-Pelvic Surgery, Department of Gynecology and Obstetrics. Intercantonal Hospital of Broye, Av. de la Colline 3, CH-1530, Payerne, Switzerland

    Arnaud Toussaint

  3. Center for Primary Care and Public Health (Unisanté), Division of Biostatistics, University of Lausanne, Rte de la Corniche 10, CH-1010, Lausanne, Switzerland

    Romain Piaget-Rossel & Patrick Taffé

  4. La Source, School of Nursing Sciences, HES-SO University of Applied Sciences and Arts of Western Switzerland, Av. Vinet 30, CH-1004, Lausanne, Switzerland

    Coraline Stormacq

  5. Materno-fœtal & Obstetrics Research Unit, Department of Gynecology, Obstetrics and Medical Genetics. University Hospital of Lausanne, Av. Pierre-Decker 2, CH-1011, Lausanne, Switzerland

    Arnaud Toussaint & Karine Lepigeon

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Appendices

Appendix

Appendix 1 Search Strategy

PubMed (search performed on April 1, 2019).

Search

Query

#1

(“Phyllodes Tumor”[Mesh] OR “phyllodes tumor*”[tiab] OR “phyllode tumor*”[tiab] OR “phyllodes tumor*”[tiab] OR “phyllode tumor*”[tiab] OR "Breast Neoplasms”[Mesh:NoExp] OR “borderline lesion” OR “Breast Neoplasms/diagnosis”[Mesh] OR “Breast Neoplasms/pathology”[Mesh] OR “Breast Neoplasms/surgery”[Mesh])

#2

(“Surgical Procedures, Operative”[Mesh:NoExp] OR “surgical management”[tiab] OR “surgical excision”[tiab] OR “surgical margin*” OR “margin*” OR “margin*”[tiab] OR “margins assessment”)

#3

(“Recurrence”[Mesh:NoExp] OR “recurrence”[tiab] OR “Fatal Outcome”[Mesh] OR “Survival Rate”[Mesh] OR "Prognosis”[Mesh:NoExp] OR “Neoplasm Recurrence, Local”[Mesh] OR “Neoplasm Recurrence, Local/prevention and control”[Mesh] OR “Neoplasm Recurrence, Local/mortality”[Mesh] OR “Incidence”[Mesh] OR “relapse” OR “Treatment Outcome”[Mesh:NoExp])

#4

#1 AND #2 AND #3

CINAHL (search performed on April 1, 2019).

Search

Query

#1

(“phyllodes tumor*” OR “phyllodes tumor*” OR “phyllode tumor*” OR (MM “Breast Neoplasms”) OR “borderline lesion” OR “Breast Neoplasms” OR (MM “Breast Neoplasms/DI/PA/SU”))

#2

((MH "Surgery, Operative") OR "surgical management" OR "surgical excision" OR (MH "Surgical Margin") OR "surgical margin" OR "margin*" OR "margins assessment")

#3

((MH "Recurrence") OR (MH "Fatal Outcome") OR "Survival Rate" OR (MM "Prognosis") OR (MH "Neoplasm Recurrence, Local") OR (MH "Incidence") OR "relapse" OR (MH "Treatment Outcomes"))

#4

#1 AND #2 AND #3

CENTRAL (search performed on April 1, 2019).

Search

Query

#1

("Phyllodes Tumor" OR "Phyllodes Tumors" "phyllodes tumor*" OR "phyllode tumor*" OR "borderline lesion" OR "Breast Neoplasms")

#2

("surgical margin*" OR "margin*" OR "Surgical Procedures, Operative" OR "surgical management" OR "margins assessment" OR "surgical excision")

#3

("Recurrence" OR "Fatal Outcome" OR "Survival Rate" OR "Prognosis" OR "Neoplasm Recurrence, Local" OR "Incidence" OR "relapse" OR "Treatment Outcome")

#4

#1 AND #2 AND #3—limits: search all text + trials

Embase (search performed on April 1, 2019).

Search

Query

#1

('phyllodes tumor'/exp OR 'phyllodes tumor' OR 'phyllodes tumor'/exp OR 'phyllode tumor' OR 'borderline lesion' OR 'breast tumor'/de)

#2

('surgical margin'/exp OR 'surgical margin' OR 'surgery'/de OR 'surgical management' OR 'margin assessment' OR 'surgical ablation'/exp OR 'surgical excision')

#3

('recurrence risk'/exp OR 'recurrence' OR 'tumor recurrence'/exp OR 'mortality rate'/de OR 'survival rate'/exp OR 'prognosis'/de OR 'incidence'/exp OR 'relapse'/exp OR 'treatment outcome'/exp OR 'tumor recurrence'/exp)

#4

#1 AND #2 AND #3

ScienceDirect (search performed on April 1, 2019).

Search

Query

#1

("Phyllodes Tumor" OR "Phyllodes Tumors" OR "phyllodes tumor" OR "phyllode tumor" OR "borderline lesion" OR "Breast Neoplasms")

#2

("surgical margin" OR "surgical margins" OR "margin" OR "margins" OR "Surgical Procedure" OR "surgical management" OR "margins assessment" OR "surgical excision" OR "surgical ablation")

#3

("Recurrence" OR "Neoplasm Recurrence" OR "Incidence" OR "relapse" OR "Treatment Outcome" OR "Fatal Outcome" OR "Survival Rate" OR "Prognosis" OR "tumor recurrence")

#4

#1 AND #2 AND #3—(limits: Journals, all years + Biochemistry, Genetics and Molecular Biology/ Medicine and Dentistry / Nursing and Health Professions)

Appendix 2

figure a

Appendix 3 Excluded studies

Sabban F, Collinet P, Lucot J-P, Boman F, Leroy J-L, Vinatier D. Tumeurs phyllodes du sein. A propos de 8 patientes. J Gynecol Obstet Biol Reprod, 2005; 34(cahier 1):252–56.

4 criteria out of ten not met, high risk of selection bias that seriously weakens confidence in the results

Sotheran W, Domjan J, Jeffrey M, Wise MH, Perry PM. Phyllodes tumors of the breast – a retrospective study from 1982–2000 of 50 cases in Portsmouth. Ann R Coll Surg Engl, 2005; 87:339–44.

5 criteria out of ten not met, high risk of selection bias that seriously weakens confidence in the results

Varghese SS, Sasidharan B, Manipadam MT, Paul MJ, Backianathan S. Radiotherapy in Phyllodes Tumor. J Clin Diag Res, 2017; 11(1):XC01-03.

5 criteria out of ten not met, high risk of selection bias that seriously weakens confidence in the results

Appendix 4

See Table 6.

Table 6 Critical appraisal checklist for case series
Full size table

Appendix 5

See Figs. 

Fig. 3
figure 3

Forest plot with empirical Bayes predictions (benign PT). LR local recurrence, DM distant metastasis

Full size image

3,

Fig. 4
figure 4

Forest plot with empirical Bayes predictions (borderline PT). LR local recurrence, DM distant metastasis

Full size image

4,

Fig. 5
figure 5

Forest plot with empirical Bayes predictions (malignant PT). LR local recurrence, DM distant metastasis

Full size image

5

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Toussaint, A., Piaget-Rossel, R., Stormacq, C. et al. Width of margins in phyllodes tumors of the breast: the controversy drags on?—a systematic review and meta-analysis. Breast Cancer Res Treat 185, 21–37 (2021). https://doi.org/10.1007/s10549-020-05924-8

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