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@ARTICLE{Wimberger:274485,
      author       = {P. Wimberger$^*$ and J.-U. Blohmer and P. Krabisch and T.
                      Link$^*$ and M. Just and B. V. Sinn and E. Simon and C.
                      Solbach and T. Fehm and C. Denkert and C. Kühn and K. Rhiem
                      and H. Tesch and S. Kümmel and A. Petzold$^*$ and O.
                      Stötzer and C. Meisel$^*$ and J. D. Kuhlmann$^*$ and V.
                      Nekljudova and S. Loibl},
      title        = {{T}he effect of denosumab on disseminated tumor cells
                      ({DTC}s) of breast cancer patients with neoadjuvant
                      treatment: a {G}epar{X} translational substudy.},
      journal      = {Breast cancer research},
      volume       = {25},
      number       = {1},
      issn         = {1465-5411},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-00628},
      pages        = {32},
      year         = {2023},
      abstract     = {Disseminated tumor cells (DTCs) in the bone marrow are
                      observed in about $40\%$ at primary diagnosis of breast
                      cancer and predict poor survival. While anti-resorptive
                      therapy with bisphosphonates was shown to eradicate minimal
                      residue disease in the bone marrow, the effect of denosumab
                      on DTCs, particularly in the neoadjuvant setting, is largely
                      unknown. The recent GeparX clinical trial reported that
                      denosumab, applied as an add-on treatment to nab-paclitaxel
                      based neoadjuvant chemotherapy (NACT), did not improve the
                      patient's pathologic complete response (pCR) rate. Herein,
                      we analyzed the predictive value of DTCs for the response to
                      NACT and interrogated whether neoadjuvant denosumab
                      treatment may eradicate DTCs in the bone marrow.A total of
                      167 patients from the GeparX trial were analyzed for DTCs at
                      baseline by immunocytochemistry using the pan-cytokeratin
                      antibody A45-B/B3. Initially DTC-positive patients were
                      re-analyzed for DTCs after NACT ± denosumab.At baseline,
                      DTCs were observed in 43/167 patients $(25.7\%)$ in the
                      total cohort, however their presence did not predict
                      response to nab-paclitaxel based NACT (pCR rates: $37.1\%$
                      in DTC-negative vs. $32.6\%$ DTC-positive; p = 0.713).
                      Regarding breast cancer subtypes, the presence of DTCs at
                      baseline was numerically associated with response to NACT in
                      TNBC patients (pCR rates: $40.0\%$ in DTC-positive vs.
                      $66.7\%$ in DTC-negative patients; p = 0.16). Overall,
                      denosumab treatment did not significantly increase the given
                      DTC-eradication rate of NACT (NACT: $69.6\%$ DTC-eradication
                      vs. NACT + denosumab: $77.8\%$ DTC-eradication; p = 0.726).
                      In TNBC patients with pCR, a numerical but statistically
                      non-significant increase of DTC-eradication after NACT +
                      denosumab was observed (NACT: $75\%$ DTC-eradication vs.
                      NACT + denosumab: $100\%$ DTC-eradication; p = 1.00).This is
                      the first study worldwide, demonstrating that neoadjuvant
                      add-on denosumab over a short-term period of 24 months does
                      not increase the DTC-eradication rate in breast cancer
                      patients treated with NACT.},
      keywords     = {Bone marrow (Other) / Denosumab (Other) / Disseminated
                      tumor cells (Other) / GeparX trial (Other) / Neoadjuvant
                      chemotherapy (Other)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36978142},
      doi          = {10.1186/s13058-023-01619-2},
      url          = {https://inrepo02.dkfz.de/record/274485},
}