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@ARTICLE{Madhavan:128027,
      author       = {D. Madhavan and M. Wallwiener and K. Bents and M.
                      Zucknick$^*$ and J. Nees and S. Schott and K. Cuk and S.
                      Riethdorf and A. Trumpp$^*$ and K. Pantel and C. Sohn and A.
                      Schneeweiss and H. Surowy$^*$ and B. Burwinkel$^*$},
      title        = {{P}lasma {DNA} integrity as a biomarker for primary and
                      metastatic breast cancer and potential marker for early
                      diagnosis.060},
      journal      = {Breast cancer research and treatment},
      volume       = {146},
      number       = {1},
      issn         = {1573-7217},
      address      = {Dordrecht [u.a.]},
      publisher    = {Springer Science + Business Media B.V.},
      reportid     = {DKFZ-2017-04049},
      pages        = {163 - 174},
      year         = {2014},
      abstract     = {Circulating or cell-free DNA (cfDNA) has been evaluated as
                      a biomarker in many cancers including breast cancer. In
                      particular, integrity of cfDNA has been shown to be altered
                      in cancers. We have estimated the biomarker potential of
                      cfDNA in primary (PBC) and metastatic breast cancer (MBC).
                      cfDNA integrity (cfDI) and concentration were determined in
                      plasma of 383 individuals, including 82 PBC and 201 MBC
                      cases, as well as 100 healthy controls, by measuring ALU and
                      LINE1 repetitive DNA elements using quantitative PCR. The
                      MBC patient group was further sub-divided into patients with
                      detectable circulating tumour cells (CTCpos-MBC, n = 100)
                      and those without (CTCneg-MBC, n = 101). A hierarchical
                      decrease in cfDI and increase in cfDNA concentration from
                      healthy controls to PBC and further onto MBC patients were
                      observed. Investigation of cfDNA in media of cell lines was
                      in concordance with these results. Combination of cfDI and
                      cfDNA concentration could differentiate PBC cases from
                      controls (area under the curve, AUC = 0.75), MBC cases
                      from controls (AUC = 0.81 for CTCneg-MBC, AUC = 0.93 for
                      CTCpos-MBC), and CTCneg-MBC from CTCpos-MBC cases
                      (AUC = 0.83). cfDI additionally demonstrated a positive
                      correlation to progression-free (HR of 0.46 for ALU,
                      P = 0.0025) and overall survival (HR of 0.15 for ALU and
                      0.20 for LINE1, P < 0.0001) in MBC, and had lower
                      prediction error than CTC status. Our findings show that
                      reduced cfDI and increased cfDNA concentration can serve as
                      diagnostic markers for PBC and MBC, and cfDI as a prognostic
                      marker for MBC, thereby making them attractive candidates
                      for blood-based multi-marker assays.},
      keywords     = {Biomarkers, Tumor (NLM Chemicals)},
      cin          = {C060 / C080 / A010},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)C080-20160331 /
                      I:(DE-He78)A010-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24838941},
      doi          = {10.1007/s10549-014-2946-2},
      url          = {https://inrepo02.dkfz.de/record/128027},
}