title: Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer.
abstract: OBJECTIVE
  The presence of disseminated tumor cells (DTCs) in bone marrow (BM) predicts survival in early breast cancer. This study explores the use of DTCs for identification of patients insufficiently treated with adjuvant therapy so they can be offered secondary adjuvant treatment and the subsequent surrogate marker potential of DTCs for outcome determination.
  
  
  METHODS
  Patients with early breast cancer who had completed six cycles of adjuvant fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy underwent BM aspiration 2 to 3 months (BM1) and 8 to 9 months (BM2) after FEC. Presence of DTCs in BM was determined by immunocytochemistry using pan-cytokeratin monoclonal antibodies. If one or more DTCs were present at BM2, six cycles of docetaxel (100 mg/m(2), once every 3 weeks) were administered, followed by DTC analysis 1 and 13 months after the last docetaxel infusion (after treatment). Cox regression analysis was used to evaluate disease-free interval (DFI).
  
  
  RESULTS
  Of 1,066 patients with a DTC result at BM2 and available follow-up information (median follow-up, 71.9 months from the time of BM2), 7.2% were DTC positive. Of 72 docetaxel-treated patients analyzed for DTCs after treatment, 15 (20.8%) had persistent DTCs. Patients with remaining DTCs had markedly reduced DFI (46.7% experienced relapse) compared with patients with no DTCs after treatment (adjusted hazard ratio, 7.58; 95% CI, 2.3 to 24.7). The docetaxel-treated patients with no DTCs after treatment had comparable DFI (8.8% experienced relapse) compared with those with no DTCs both at BM1 and BM2 (12.7% experienced relapse; P = .377, log-rank test).
  
  
  CONCLUSIONS
  DTC status identifies high-risk patients after FEC chemotherapy, and DTC monitoring status after secondary treatment with docetaxel correlated strongly with survival. This emphasizes the potential for DTC analysis as a surrogate marker for adjuvant treatment effect in breast cancer.
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway. bjorn.naume@medisin.uio.no.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Synnestvedt
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Ragnhild Sørum
authors.initials: RS
authors.lastname: Falk
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Gro
authors.initials: G
authors.lastname: Wiedswang
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Weyde
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Risberg
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Christian
authors.initials: C
authors.lastname: Kersten
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Ingvil
authors.initials: I
authors.lastname: Mjaaland
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Lise
authors.initials: L
authors.lastname: Vindi
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Hilde H
authors.initials: HH
authors.lastname: Sommer
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Anna Barbro
authors.initials: AB
authors.lastname: Sætersdal
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Maria Christine
authors.initials: MC
authors.lastname: Rypdal
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Bendigtsen Schirmer
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Erik Andreas
authors.initials: EA
authors.lastname: Wist
authors.affiliation: Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Borgen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D007633:Keratins / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D009664:Norway; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019233:Retreatment; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D007633:Keratins; D003520:Cyclophosphamide; D005472:Fluorouracil