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WebPage:
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         headline:Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
         description:Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. Bone marrow and peripheral blood were collected before NACT (BM1: n = 231/PB1: n = 219), at surgery (BM2: n = 69/PB2: n = 71), and after 12 months from start of NACT (BM3: n = 162/PB3: n = 141). Patients were included from 1997 to 2003 and followed until 2009 (or ten years follow-up). DTC- and CTC-status were determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. The prognostic significance of DTCs/CTCs was assessed by univariate and multivariate Cox-regression analyses. Before NACT, DTCs and CTCs were detected in 21.2% and 4.9% of the patients, respectively. At surgery, 15.9% and 1.4% had DTC- and CTC-presence, compared to 26.5% and 4.3% at 12 months from start of NACT. Of patients for whom DTC results both before NACT and at 12 months were available, concordant results were observed in 68%, and 14 out of 65 had positive DTC-status at both time points. Presence of ≥ 1 DTC 12 months from start of NACT, but not at other time points, predicted reduced disease-free survival (DFS; HR 2.3, p = 0.003), breast cancer-specific survival (BCSS; HR 3.0, p < 0.001) and overall survival (OS; HR 2.8, p < 0.001). Before NACT, presence of ≥ 3 DTCs was also associated with unfavorable outcome, and reduced BCSS was observed for CTC-positive patients (HR 2.2, p = 0.046). In multivariate analysis, DTC status (</≥ 1 DTC) at 12 months after start of NACT remained as a prognostic factor for both DFS (HR 2.2, p = 0.005), BCSS (HR 2.6, p = 0.002) and OS (HR 2.6, p = 0.002). The survival for patients with change in DTC-status was determined by the DTC-status at 12 months. Presence of DTCs after NACT indicated high risk for relapse and death, irrespective of the DTC-status before treatment. The results supports the potential use of DTC analysis as a monitoring tool during follow up, for selection of patients to secondary treatment intervention within clinical trials.
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            Overall Survival
            Advanced Breast Cancer
            Circulate Tumor Cell
            Bone Marrow Aspiration
            Disseminate Tumor Cell
            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
      description:Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. Bone marrow and peripheral blood were collected before NACT (BM1: n = 231/PB1: n = 219), at surgery (BM2: n = 69/PB2: n = 71), and after 12 months from start of NACT (BM3: n = 162/PB3: n = 141). Patients were included from 1997 to 2003 and followed until 2009 (or ten years follow-up). DTC- and CTC-status were determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. The prognostic significance of DTCs/CTCs was assessed by univariate and multivariate Cox-regression analyses. Before NACT, DTCs and CTCs were detected in 21.2% and 4.9% of the patients, respectively. At surgery, 15.9% and 1.4% had DTC- and CTC-presence, compared to 26.5% and 4.3% at 12 months from start of NACT. Of patients for whom DTC results both before NACT and at 12 months were available, concordant results were observed in 68%, and 14 out of 65 had positive DTC-status at both time points. Presence of ≥ 1 DTC 12 months from start of NACT, but not at other time points, predicted reduced disease-free survival (DFS; HR 2.3, p = 0.003), breast cancer-specific survival (BCSS; HR 3.0, p < 0.001) and overall survival (OS; HR 2.8, p < 0.001). Before NACT, presence of ≥ 3 DTCs was also associated with unfavorable outcome, and reduced BCSS was observed for CTC-positive patients (HR 2.2, p = 0.046). In multivariate analysis, DTC status (</≥ 1 DTC) at 12 months after start of NACT remained as a prognostic factor for both DFS (HR 2.2, p = 0.005), BCSS (HR 2.6, p = 0.002) and OS (HR 2.6, p = 0.002). The survival for patients with change in DTC-status was determined by the DTC-status at 12 months. Presence of DTCs after NACT indicated high risk for relapse and death, irrespective of the DTC-status before treatment. The results supports the potential use of DTC analysis as a monitoring tool during follow up, for selection of patients to secondary treatment intervention within clinical trials.
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      dateModified:2012-08-14T00:00:00Z
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      pageEnd:13
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      sameAs:https://doi.org/10.1186/bcr3242
      keywords:
         Overall Survival
         Advanced Breast Cancer
         Circulate Tumor Cell
         Bone Marrow Aspiration
         Disseminate Tumor Cell
         Cancer Research
         Oncology
         Surgical Oncology
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            name:University of Oslo
            address:
               name:Institute of Clinical medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
               type:PostalAddress
            type:Organization
      name:Gun Anker
      affiliation:
            name:University of Bergen
            address:
               name:Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway
               type:PostalAddress
            type:Organization
            name:Haukeland University Hospital
            address:
               name:Department of Oncology, Haukeland University Hospital, Bergen, Norway
               type:PostalAddress
            type:Organization
      name:Bjørn Østenstad
      affiliation:
            name:Oslo University Hospital
            address:
               name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
               type:PostalAddress
            type:Organization
      name:Steinar Lundgren
      affiliation:
            name:St. Olav University Hospital
            address:
               name:Department of Oncology, St. Olav University Hospital, Trondheim, Norway
               type:PostalAddress
            type:Organization
            name:Norwegian University of Science and Technology
            address:
               name:Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
               type:PostalAddress
            type:Organization
      name:Terje Risberg
      affiliation:
            name:University Hospital of Northern Norway and Institute of Clinical Medicine, University of Tromsø
            address:
               name:Department of Oncology, University Hospital of Northern Norway and Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway
               type:PostalAddress
            type:Organization
      name:Ingvil Mjaaland
      affiliation:
            name:Stavanger University Hospital
            address:
               name:Division of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway
               type:PostalAddress
            type:Organization
      name:Gunnar Kvalheim
      affiliation:
            name:Oslo University Hospital
            address:
               name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
               type:PostalAddress
            type:Organization
      name:Per Eystein Lønning
      affiliation:
            name:University of Bergen
            address:
               name:Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway
               type:PostalAddress
            type:Organization
            name:Haukeland University Hospital
            address:
               name:Department of Oncology, Haukeland University Hospital, Bergen, Norway
               type:PostalAddress
            type:Organization
      name:Bjørn Naume
      affiliation:
            name:Oslo University Hospital
            address:
               name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
               type:PostalAddress
            type:Organization
            name:University of Oslo
            address:
               name:Institute of Clinical medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Radium Hospital, Oslo, Norway
      name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
      name:Department of Pathology, Oslo University Hospital, The Radium Hospital, Oslo, Norway
      name:Department of Pathology, Oslo University Hospital, The Radium Hospital, Oslo, Norway
      name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
      name:Department of Pathology, Oslo University Hospital, The Radium Hospital, Oslo, Norway
      name:Institute of Clinical medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
      name:Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway
      name:Department of Oncology, Haukeland University Hospital, Bergen, Norway
      name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
      name:Department of Oncology, St. Olav University Hospital, Trondheim, Norway
      name:Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
      name:Department of Oncology, University Hospital of Northern Norway and Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway
      name:Division of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway
      name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
      name:Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway
      name:Department of Oncology, Haukeland University Hospital, Bergen, Norway
      name:Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway
      name:Institute of Clinical medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

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