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Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing



A paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT.


We performed an 11-institution review of contemporary (2007–2017) PT practice. We recorded multigenerational family history and personal history of genetic testing. We identified patients meeting NCCN criteria for genetic evaluation. Logistic regression estimated the association of select covariates with likelihood of undergoing genetic testing.


Of 550 PT patients, 59.8% (n = 329) had a close family history of cancer, and 34.0% (n = 112) had ≥ 3 family members affected. Only 6.2% (n = 34) underwent genetic testing, 38.2% (n = 13) of whom had only BRCA1/BRCA2 tested. Of 34 patients tested, 8.8% had a deleterious mutation (1 BRCA1, 2 TP53), and 5.9% had a BRCA2 VUS. Of women who had TP53 testing (N = 21), 9.5% had a mutation. Selection for testing was not associated with age (odds ratio [OR] 1.01, p = 0.55) or PT size (p = 0.12) but was associated with grade (malignant vs. benign: OR 9.17, 95% CI 3.97–21.18) and meeting NCCN criteria (OR 3.43, 95% confidence interval 1.70–6.94). Notably, an additional 86 (15.6%) patients met NCCN criteria but had no genetic testing.


Very few women with PT undergo germline testing; however, in those selected for testing, a deleterious mutation was identified in ~ 10%. Multigene testing of a PT cohort would present an opportunity to discover the true incidence of germline mutations in PT patients.

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  1. 1.

    Muller J. Uber den feineran Bau and die Formen der krankhaften art Geschwulste. Berlin, Germany: G Reimer, 1838(54).

  2. 2.

    Rosen PP, Oberman HA. Tumors of the mammary gland. Washington, DC: Armed Forces Institute of Pathology, 1993.

    Google Scholar 

  3. 3.

    Rosen PP. Rosen’s breast pathology, 2nd edn. Lippincott William Wilkins, New York, 2001.

  4. 4.

    Tan PH, Ellis IO. Myoepithelial and epithelial-myoepithelial, mesenchymal and fibroepithelial breast lesions: updates from the WHO Classification of Tumours of the Breast 2012. J Clin Pathol. 2013; 66:465–70.

    CAS  Article  Google Scholar 

  5. 5.

    Zhang Y, Kleer CG. Phyllodes tumor of the breast: histopathologic features, differential diagnosis, and molecular/genetic updates. Arch Pathol Lab Med. 2016;140:665–71.

    Article  Google Scholar 

  6. 6.

    Yom CK, Han W, Kim SW, Park SY, Park IA, Noh DY. 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.

    Article  Google Scholar 

  7. 7.

    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.

    Article  Google Scholar 

  8. 8.

    Cheng SP, Chang YC, Liu TP, Lee JJ, Tzen CY, Liu CL. Phyllodes tumor of the breast: the challenge persists. World J Surg. 2006;30:1414-21.

    Article  Google Scholar 

  9. 9.

    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.

    Article  Google Scholar 

  10. 10.

    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.

    Article  Google Scholar 

  11. 11.

    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.

    Article  Google Scholar 

  12. 12.

    Rajan PB, Cranor ML, Rosen PP. Cystosarcoma phyllodes in adolescent girls and young women: a study of 45 patients. Am J Pathol. 1998; 22:64–9.

    CAS  Article  Google Scholar 

  13. 13.

    Salvadori B, Cusumano F, Del Bo R, et al. Surgical treatment of phyllodes tumors of the breast. Cancer. 1989;63:2532–6.

    CAS  Article  Google Scholar 

  14. 14.

    National Comprehensive Cancer Network. NCCN, Clinical Practice Guidelines in Oncology: Breast Cancer, Version, 3.2019. Available at: Accessed 9 Dec 2019.

  15. 15.

    Foucar CE, Hardy A, Siziopikou KP, et al. A mother and daughter with phyllodes tumors of the breast. Clinical Breast Cancer. 2012;12:373-377.

    Article  Google Scholar 

  16. 16.

    Wang Y, Zhu J, Gou J, Xiong J, Yang X. Phyllodes tumors of the breast in 2 sisters: case report and review of literature. Medicine. 2017;96:e8552.

    Article  Google Scholar 

  17. 17.

    Rhiem K, Flucke U, Engel C, et al. Association of the BRCA1 missense variant R1699W with a malignant phyllodes tumor of the breast. Cancer Genet Cytogenet. 2007;176:76–9.

    CAS  Article  Google Scholar 

  18. 18.

    Shearer DD, et al. Malignant phyllodes tumor in a patient with hereditary retinoblastoma: a case report and literature review. Proc Obstet Gynecol. 2013;3(2):5.

    Google Scholar 

  19. 19.

    Mak J. Two cases of malignant phyllodes tumor in patients with history of bilateral retinoblastoma—a possible novel association with RB1 germline mutations. ASHG American Society of Human Genetics Annual Meeting; October 23-27, 2007; San Diego, CA. Available at: Accessed 27 Oct 2019.

  20. 20.

    Birch JM, Alston RD, McNally RJ, et al. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 2001;20:4621-8.

    CAS  Article  Google Scholar 

  21. 21.

    Giacomazzi J, Koehler-Santos P, Palmero EI, et al. A TP53 founder mutation, p.R337H, is associated with phyllodes breast tumors in Brazil. Virchows Arch. 2013;463:17–22.

    CAS  Article  Google Scholar 

  22. 22.

    Bot FJ, Sleddens HF, Dinjens WN. Molecular assessment of clonality leads to the identification of a new germ line TP53 mutation associated with malignant cystosarcoma phyllodes and soft tissue sarcoma. Diagn Molec Pathol. 1998;7:295-301.

    CAS  Article  Google Scholar 

  23. 23.

    Prochazkova K, Foretova L, Sedlacek Z. A rare tumor and an ethical dilemma in a family with a germline TP53 mutation. Cancer Genetic Cytogenet. 2008;180:65–69.

    CAS  Article  Google Scholar 

  24. 24.

    National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 3.2019. Available at: Accessed 27 Oct 2019.

  25. 25.

    Beitsch PD, Whitworth PW, Hughes K, et al. Underdiagnosis of hereditary breast cancer: are genetic testing guidelines a tool or an obstacle? J Clin Oncol. 2019;37:453–60.

    Article  Google Scholar 

  26. 26.

    U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on November 2018 submission data (1999-2016): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. Available at: Accessed 30 Dec 2019.

  27. 27.

    Chompret A, Brugieres L, Ronsin M, et al. p53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer. 2000; 82:1932–7.

    CAS  Article  Google Scholar 

  28. 28.

    Gonzalez KD, Buzin CH, Noltner KA, et al. High frequency of de novo mutations in Li-Fraumeni Syndrome. J Med Genet. 2009;46:689–93.

    CAS  Article  Google Scholar 

  29. 29.

    Macdonald OK, Lee CM, Tward JD, Chappel CD, Gaffney DK. Malignant phyllodes tumor of the female breast: association of primary therapy with cause-specific survival from the Surveillance, Epidemiology, and End Results (SEER) program. Cancer. 2006;107:2127–33.

    Article  Google Scholar 

  30. 30.

    Kim YJ, Kim K. Radiation therapy for malignant phyllodes tumor of the breast: an analysis of SEER Data. Breast. 2017;32:26–32.

    Article  Google Scholar 

  31. 31.

    Gnerlich JL, Williams RT, Jaskowiak N, Kulkarni SA. Utilization of radiotherapy for malignant phyllodes tumors: analysis of the National Cancer Data Base, 1998–2009. Ann Surg Oncol. 2014;21:1222-30.

    Article  Google Scholar 

  32. 32.

    Belkacemi Y, Bousquet G, Marsiglia H, et al. Phyllodes tumor of the breast. Int J Radiat Oncol Biol Phys. 2008;70:492-500.

    Article  Google Scholar 

  33. 33.

    Barth RJ Jr, Wells WA, Mitchell SE, Cole BF. A prospective, multi-institutional study of adjuvant radiotherapy after resection of malignant phyllodes tumors. Ann Surg Oncol. 2009;16:2288–94.

    Article  Google Scholar 

  34. 34.

    Zeng S, Zhang X, Yang D, Wang X, Ren G. Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: a systemic review and meta-analysis. Mol Clin Oncol. 2015;3:663–71.

    CAS  Article  Google Scholar 

  35. 35.

    Moskowitz CS, Chou JF, Wolden SL, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217–23.

    Article  Google Scholar 

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This publication was made possible (in part) by philanthropic funds through the generosity of Sara and Bruce Brandaleone. Statistical support was funded by the Duke Cancer Institute through NIH Grant P30CA014236 (PI: Kastan).


This publication was made possible (in part) by philanthropic funds through the generosity of Sara and Bruce Brandaleone. Statistical support was funded by the Duke Cancer Institute through NIH grant P30CA014236 (PI: Kastan).

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Correspondence to Laura H. Rosenberger MD.

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Rosenberger, L.H., Thomas, S.M., Nimbkar, S.N. et al. Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing. Ann Surg Oncol 27, 3633–3640 (2020).

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