Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia

Jane E. Churpek*, Rafael Marquez, Barbara Neistadt, Kimberly Claussen, Ming K. Lee, Matthew M. Churpek, Dezheng Huo, Howard Weiner, Mekhala Bannerjee, Lucy A. Godley, Michelle M. Le Beau, Colin C. Pritchard, Tom Walsh, Mary Claire King, Olufunmilayo I. Olopade, Richard A. Larson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


BACKGROUND Risk factors for the development of therapy-related leukemia (TRL), an often lethal late complication of cytotoxic therapy, remain poorly understood and may differ for survivors of different malignancies. Survivors of breast cancer (BC) now account for the majority of TRL cases, making the study of TRL risk factors in this population a priority. METHODS Subjects with TRL after cytotoxic therapy for a primary BC were identified from the TRL registry at The University of Chicago. Those with an available germline DNA sample were screened with a comprehensive gene panel covering known inherited BC susceptibility genes. Clinical and TRL characteristics of all subjects and those with identified germline mutations were described. RESULTS Nineteen of 88 survivors of BC with TRL (22%) had an additional primary cancer and 40 of the 70 survivors with an available family history (57%) had a close relative with breast, ovarian, or pancreatic cancer. Of the 47 subjects with available DNA, 10 (21%) were found to carry a deleterious inherited mutation in BRCA1 (3 subjects; 6%), BRCA2 (2 subjects; 4%), TP53 (tumor protein p53) (3 subjects; 6%), CHEK2 (checkpoint kinase 2) (1 subject; 2%), and PALB2 (partner and localizer of BRCA2) (1 subject; 2%). CONCLUSIONS Survivors of BC with TRL have personal and family histories suggestive of inherited cancer susceptibility and frequently carry germline mutations in BC susceptibility genes. The data from the current study support the role of these genes in TRL risk and suggest that long-term follow-up studies of women with germline mutations who are treated for BC and functional studies of the effects of heterozygous mutations in these genes on bone marrow function after cytotoxic exposures are warranted.

Original languageEnglish (US)
Pages (from-to)304-311
Number of pages8
Issue number2
StatePublished - Jan 15 2016


  • breast cancer
  • inherited
  • leukemia
  • therapy-related

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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