BRCA2 Loss-of-Function and High Sensitivity to Cisplatin-Based Chemotherapy in a Patient With a Pleomorphic Soft Tissue Sarcoma: Effect of Genomic Medicine

Am J Med Sci. 2018 Oct;356(4):404-407. doi: 10.1016/j.amjms.2018.04.015. Epub 2018 May 1.


We report the case of a patient with a BRCA2 germline mutation who developed a localized pleomorphic soft tissue sarcoma of the leg with poor prognostic features. BRCA2 germline mutations were not previously reported to be associated with pleomorphic sarcoma. BRCA2 loss-of-heterozygosity was found in the tumor, resulting in a complete BRCA2 loss-of-function. BRCA2 deficiency is associated with sensitivity to cisplatin-based chemotherapy in breast and ovarian cancer patients. We used a cisplatin-based chemotherapy. A rapid major partial response was obtained, which allowed a curative and conservative surgical resection of the sarcoma followed by adjuvant irradiation. This case illustrates that sarcoma patients may present unexpected but targetable genetic abnormalities and that BRCA2 loss-of-function may be targetable in sarcoma as it is associated with enhanced sensitivity to cisplatin. Our observation emphasizes the input of genomic medicine in clinical practice, its importance for treatment decisions, and the overlap between constitutional and somatic genetics.

Keywords: BRCA2; Cancer predisposition; Cisplatin; Genomic medicine; Pleomorphic sarcoma.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • BRCA2 Protein / genetics*
  • BRCA2 Protein / metabolism
  • Breast Neoplasms / genetics
  • Cisplatin / pharmacology*
  • Female
  • Germ-Line Mutation*
  • Humans
  • Loss of Function Mutation*
  • Middle Aged
  • Ovarian Neoplasms / genetics
  • Sarcoma / drug therapy*
  • Sarcoma / genetics


  • Antineoplastic Agents
  • BRCA2 Protein
  • BRCA2 protein, human
  • Cisplatin