Breast Cancer Research and Treatment

, Volume 155, Issue 1, pp 139–149 | Cite as

Cell-free DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients

  • Diana H. Liang
  • Joe E. Ensor
  • Zhe-bin Liu
  • Asmita Patel
  • Tejal A. Patel
  • Jenny C. Chang
  • Angel A. RodriguezEmail author


Due to the spatial and temporal genomic heterogeneity of breast cancer, genomic sequencing obtained from a single biopsy may not capture the complete genomic profile of tumors. Thus, we propose that cell-free DNA (cfDNA) in plasma may be an alternate source of genomic information to provide comprehensive data throughout a patient’s clinical course. We performed a retrospective chart review of 100 patients with stage 4 or high-risk stage 3 breast cancer. The degree of agreement between genomic alterations found in tumor DNA (tDNA) and cfDNA was determined by Cohen’s Kappa. Clinical disease progression was compared to mutant allele frequency using a two-sided Fisher’s exact test. The presence of mutations and mutant allele frequency was correlated with progression-free survival (PFS) using a Cox proportional hazards model and a log-rank test. The most commonly found genomic alterations were mutations in TP53 and PIK3CA, and amplification of EGFR and ERBB2. PIK3CA mutation and ERBB2 amplification demonstrated robust agreement between tDNA and cfDNA (Cohen’s kappa = 0.64 and 0.77, respectively). TP53 mutation and EGFR amplification demonstrated poor agreement between tDNA and cfDNA (Cohen’s kappa = 0.18 and 0.33, respectively). The directional changes of TP53 and PIK3CA mutant allele frequency were closely associated with response to therapy (p = 0.002). The presence of TP53 mutation (p = 0.0004) and PIK3CA mutant allele frequency [p = 0.01, HR 1.074 (95 % CI 1.018–1.134)] was excellent predictors of PFS. Identification of selected cancer-specific genomic alterations from cfDNA may be a noninvasive way to monitor disease progression, predict PFS, and offer targeted therapy.


Cell-free DNA Breast cancer Clinical markers 



This project was supported by the Houston Methodist Cancer Center.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Approval for the study was obtained from the institutional review board of the Houston Methodist Hospital. For this retrospective study, formal consent is not required.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Diana H. Liang
    • 1
    • 2
  • Joe E. Ensor
    • 2
    • 3
  • Zhe-bin Liu
    • 2
    • 4
  • Asmita Patel
    • 3
  • Tejal A. Patel
    • 3
  • Jenny C. Chang
    • 3
  • Angel A. Rodriguez
    • 3
    Email author
  1. 1.Department of SurgeryHouston Methodist HospitalHoustonUSA
  2. 2.Houston Methodist Research InstituteHouston Methodist HospitalHoustonUSA
  3. 3.Houston Methodist Cancer CenterHoustonUSA
  4. 4.Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina

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