Metastatic breast cancer is a leading cause  of cancer-related deaths
   in women  worldwide.   Patients  with  triple  negative breast cancer
   (TNBCs), a highly aggressive tumor subtype, have  a particularly poor
   prognosis.  Multiple reports demonstrate that altered  content of the
   multicopy  mitochondrial  genome  (mtDNA)  in  primary breast  tumors
   correlates with poor prognosis.  We earlier reported  that mtDNA copy
   number   reduction   in   breast   cancer   cell   lines  induces  an
   epithelial-mesenchymal   transition   associated   with   metastasis.
   However, it  is  unknown  whether  the  breast  tumor subtypes (TNBC,
   Luminal and HER2+) differ in the nature  and  amount of mitochondrial
   defects and if mitochondrial  defects  can  be  used  as  a marker to
   identify tumors at risk for metastasis.   By  analyzing human primary
   tumors, cell lines and the TCGA dataset, we demonstrate a high degree
   of variability in mitochondrial defects among the  tumor subtypes and
   TNBCs,  in  particular,  exhibit  higher  frequency of  mitochondrial
   defects, including reduced  mtDNA  content,  mtDNA sequence imbalance
   (mtRNR1:ND4), impaired mitochondrial respiration and metabolic switch
   to glycolysis which is associated with tumorigenicity.  We identified
   that genes involved in  maintenance  of  mitochondrial structural and
   functional integrity are differentially  expressed  in TNBCs compared
   to non-TNBC tumors.   Furthermore,  we  identified  a  subset of TNBC
   tumors  that  contain   lower   expression   of  epithelial  splicing
   regulatory protein  (ESRP)-1,  typical  of  metastasizing cells.  The
   overall impact of our findings  reported  here  is that mitochondrial
   heterogeneity among TNBCs can be used  to  identify  TNBC patients at
   risk of metastasis and the altered metabolism and metabolic genes can
   be targeted to improve chemotherapeutic response.

   (Molecular Basis of Disease, Volume 1864, Issue 4(A), Pages 1060-1071
    doi:10.1016/j.bbadis.2018.01.002, 2018)