Brain Metastasis Prediction by Transcriptomic Profiling in Triple-Negative Breast Cancer

Clin Breast Cancer. 2017 Apr;17(2):e65-e75. doi: 10.1016/j.clbc.2016.08.008. Epub 2016 Sep 8.


Background: Triple-negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen receptor α and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of TNBC transcriptomic profiles associated with high risk of brain metastasis (BM) might identify patients requiring alternative, more aggressive, or specific preventive and therapeutic approaches.

Patients and methods: Using a cDNA-mediated annealing, selection, extension, and ligation assay, we investigated expression of 29,369 gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery cohort A and 48 in independent cohort B-that included best discriminating genes. Expression of mRNA was correlated with the occurrence of symptomatic BM.

Results: In cohort A, the difference at the noncorrected P < .005 was found for 64 transcripts (P = .23 for global test), but none showed significant difference at a preset level of false-discovery rate of < 10%. Of the 30 transcripts with the largest differences between patients with and without BM in cohort A, none was significantly associated with BM in cohort B.

Conclusion: Analysis based on the primary tumor gene transcripts alone is unlikely to predict BM development in advanced TNBC. Despite its negative findings, the study adds to the knowledge on the biology of TNBC and paves the way for future projects using more advanced molecular assays.

Keywords: Brain metastasis; Selection; Transcriptomic profiling; Triple negative breast cancer; cDNA-mediated annealing, extension, and ligation (DASL) assay.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / epidemiology
  • Brain Neoplasms / secondary
  • Estrogen Receptor alpha / metabolism
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / metabolism
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology


  • Biomarkers, Tumor
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • RNA, Messenger
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2