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Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort

  • Epidemiology
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Abstract

Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopathologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22–46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer.

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Acknowledgments

The authors gratefully acknowledge the expert technical assistance of the Dana Farber Harvard Cancer Center Specialized Histopathology Core Laboratory, particularly Teri Bowman and Donna Skinner for assistance with slide preparation, as well as Chungdak Namgyal for construction of the tissue microarray, Mei Zheng for immunohistochemistry, and Krishan Taneja for fluorescence in situ hybridization. Dana-Farber/Harvard Cancer Center is supported in part by NCI Cancer Center Support Grant # NIH 5 P30 CA06516. This research is supported in part by the Dana-Farber/Harvard SPORE in Breast Cancer (CA 89393). The City of Hope Clinical Cancer Genetics Community Research Network is supported in part by Award Number RC4A153828 (PI: JN Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. Supported by NCI P30 CA014089-37 (S. Gruber). Partially funded by a Hellenic Society of Medical Oncology (HeSMO) scholarship (G. Lypas).

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue–D1123, Boston, MA, 02215, USA

    Serena Masciari, Michelle Rath, Georgios Lypas & Judy E. Garber

  2. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Deborah A. Dillon

  3. Clinical Genetics and Breast Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Mark Robson

  4. Division of Clinical Cancer Genetics, City of Hope National Medical Center, Duarte, CA, USA

    Jeffrey N. Weitzel

  5. Hospital Vall d’Hebron, Barcelona, Spain

    Judith Balmana

  6. Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA

    Stephen B. Gruber

  7. Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA

    James M. Ford, Alexandra Lebensohn & Melinda Telli

  8. Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    David Euhus

  9. Department of Pathology, Faulkner Hospital, Boston, MA, USA

    Stephen M. Pochebit

Authors
  1. Serena Masciari
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  2. Deborah A. Dillon
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  3. Michelle Rath
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  5. Jeffrey N. Weitzel
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  7. Stephen B. Gruber
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  8. James M. Ford
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  9. David Euhus
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  10. Alexandra Lebensohn
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  11. Melinda Telli
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  12. Stephen M. Pochebit
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  13. Georgios Lypas
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  14. Judy E. Garber
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Corresponding author

Correspondence to Judy E. Garber.

Additional information

Serena Masciari and Deborah A. Dillon contributed equally to the manuscript.

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Masciari, S., Dillon, D.A., Rath, M. et al. Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort. Breast Cancer Res Treat 133, 1125–1130 (2012). https://doi.org/10.1007/s10549-012-1993-9

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  • DOI: https://doi.org/10.1007/s10549-012-1993-9

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