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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

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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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Acknowledgments

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).

Funding

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).

Author information

Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    Laura H. Rosenberger MD

  2. Duke Cancer Institute, Duke University, Durham, NC, USA

    Laura H. Rosenberger MD & Samantha M. Thomas MS

  3. Biostatistics and Bioinformatics, Duke University, Durham, NC, USA

    Samantha M. Thomas MS

  4. Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

    Suniti N. Nimbkar MD

  5. Department of Surgery, Mayo Clinic, Rochester, MN, USA

    Tina J. Hieken MD & James W. Jakub MD

  6. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    Kandice K. Ludwig MD

  7. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lisa K. Jacobs MD

  8. Department of Surgery, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Megan E. Miller MD

  9. Department of Surgery, University of North Carolina, Chapel Hill, NC, USA

    Kristalyn K. Gallagher DO

  10. Department of Surgery, University of California, San Francisco, San Francisco, CA, USA

    Jasmine Wong MD

  11. Department of Surgery, University of Wisconsin, Madison, WI, USA

    Heather B. Neuman MD

  12. Department of Surgery, University of Chicago Medicine, Chicago, IL, USA

    Jennifer Tseng MD

  13. Department of Surgery, University of Virginia Health System, Charlottesville, VA, USA

    Taryn E. Hassinger MD

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  1. Laura H. Rosenberger MD
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  2. Samantha M. Thomas MS
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  3. Suniti N. Nimbkar MD
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  4. Tina J. Hieken MD
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  8. Kristalyn K. Gallagher DO
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  13. James W. Jakub MD
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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). https://doi.org/10.1245/s10434-020-08480-z

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  • DOI: https://doi.org/10.1245/s10434-020-08480-z

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