Summary

  • TNBC patients relapses due to resistance to chemotherapy.
  • Unresolved question: is it caused by the selection of rare pre-existing clones or alternatively through the acquisition of new genomic aberrations.
  • Applied scDNA and scRNA sequencing as well as bulk exome sequencing over time for 20 TNBC patients, undergoing NAC.
  • 10 patients developed resistance (clones persisted).
  • In 8 patients, 900 cells went through DNA-seq and 6,862 cells went through RNA-seq.
  • Conclusion: Resistant genotypes were pre-existing and adaptively selected by NAC.

TNBC

  • Affects 12-18 of breast cancer patients.
  • Lacks estrogen receptor , progesterone receptor, and HER2 receptor and therefore, not eligible for hormone or anti-HER2 therapy.
  • Has shown high levels of somatic mutations and complex aneuploid rearrangements that results in extensive intra-tumor heterogeneity (ITH).
  • Difficult to resolve ITH and detect genomic information in rare subpopulations.

Single-cells

  • scDNA and scRNA emerged as powerful tools for resolving ITH, reconstructing evolutionary lineages, and detecting rare subpopulations.
    • From bulk, difficult to detect rare subpopulations or reconstruct clonal evolution?

Data collection

  • Tumor specimen frozen pre-treatment.
  • After two cycles of therapy.
  • During surgical excision after six cycles of NAC.