Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome

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Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor–positive/progesterone receptor–positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

Correspondence: Eve Henry, MD, 300 Pasteur Drive, Room S-101, Stanford CA 94305. E-mail address: eve.henry@gmail.com
  • 1

    Olivier M, Goldgar DE, Sodha N. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res 2003;63:66436650.

    • Search Google Scholar
    • Export Citation
  • 2

    Gonzalez KD, Noltner KA, Buzin CH. Beyond Li Fraumeni syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol 2009;27:12501256.

    • Search Google Scholar
    • Export Citation
  • 3

    Lustbader ED, Williams WR, Bondy ML. Segregation analysis of cancer in families of childhood soft tissue sarcoma patients. Am J Hum Genet 1992;51:344356.

    • Search Google Scholar
    • Export Citation
  • 4

    Hisada M, Garber JE, Fung CY. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 1998;90:606611.

  • 5

    Limacher JM, Frebourg T, Natarajan-Ame S, Bergerat JP. Two metachronous tumours in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer 2001;96:238242.

    • Search Google Scholar
    • Export Citation
  • 6

    Cohen RJ, Curtis RE, Inskip PD, Fraumeni JF Jr. The risk of developing second cancers among survivors of childhood soft tissue sarcoma. Cancer 2005;103:23912396.

    • Search Google Scholar
    • Export Citation
  • 7

    Kony SJ, de Vathaire F, Chrompret A. Radiation and genetic factors in the risk of second malignant neoplasm’s after a first cancer in childhood. Lancet 1997;350:9195.

    • Search Google Scholar
    • Export Citation
  • 8

    Li FP, Fraumeni JF Jr, Mulvihill JJ. A cancer family syndrome in twenty-four kindreds. Cancer Res 1988;48:53585362.

  • 9

    Heymann S, Delaloge S, Rahal A. Radio-induced malignancies after breast cancer post operative radiotherapy in patients with Li-Fraumeni syndrome. Radiat Oncol 2010;5:104109.

    • Search Google Scholar
    • Export Citation
  • 10

    Tinat J, Bougeard G, Baert-Desurmont S. 2009 version of the Chrompret criteria for Li-Fraumeni syndrome. J Clin Oncol 2009;27:108109.

  • 11

    Greenburg CC, Lipsitz SR, Hughs ME. Institutional variation in the surgical treatment of breast cancer: a study of the NCCN. Ann Surg 2011;254:339345.

    • Search Google Scholar
    • Export Citation
  • 12

    Limacher JM, Frebourg T, Natarajan-Ame S, Bergerat JP. Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer 2001;96:238242.

    • Search Google Scholar
    • Export Citation
  • 13

    Pierce LJ, Haffty BG. Radiotherapy in the treatment of hereditary breast cancer. Semin Radiat Oncol 2011;21:4350.

  • 14

    Rubino C, de Vathaire F, Shamsaldin A. Radiation dose, chemotherapy, hormonal treatment and risk of second cancer after breast cancer treatment. Br J Cancer 2003;895:840846.

    • Search Google Scholar
    • Export Citation
  • 15

    Kleinerman RA. Radiation-sensitivie gentetically susceptible pediatric sub-populations. Pediatr Radiol 2009;39(Suppl 1):S2731.

  • 16

    Schneider K, Garber J. Li-Fraumeni syndrome. In: Pagon RA, Bird TD, Dolan CR, eds. Gene Reviews. Seattle, WA: University of Washington; 1999.

  • 17

    Daly MB, Axilbund JE, Buys S. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1, 2012. Available at NCCN.org. Accessed June 18, 2012.

    • Search Google Scholar
    • Export Citation
  • 18

    Gonzalez KD, Buzin CH, Noltner KA, High frequency of de novo mutations in Li-Fraumeni. J Med Genet 2009;46:689693.

  • 19

    Malkin D, Smyth K, Shuman C. Establishment of a dedicated cancer genetics program in a tertiary pediatric center [abstract]. Am J Hum Genet 1999;65:Abstract 386.

    • Search Google Scholar
    • Export Citation
  • 20

    Masciari S, Dillon D, Dick MG. Breast cancer phenotype in women with TP53 germ-line mutations: an LFS consortium effort [abstract]. J Clin Oncol 2011;29(Suppl):Abstract 1519.

    • Search Google Scholar
    • Export Citation
  • 21

    Wilson JR, Bateman AC, Hansons H. A novel Her2 positive breast cancer phenotype arising from germline TP53 mutations. J Med Genet 2010;47:771774.

    • Search Google Scholar
    • Export Citation
  • 22

    Melhem-Bertrandt A, Bojadzieva J, Ready KJ. Early onset Her2-positive breast cancer is associated with germline TP53 mutations. Cancer 2012;118:908913.

    • Search Google Scholar
    • Export Citation
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