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Open Access Research article

Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study

Marit Synnestvedt1, Elin Borgen2, Erik Wist113, Gro Wiedswang4, Kjetil Weyde5, Terje Risberg6, Christian Kersten7, Ingvil Mjaaland8, Lise Vindi9, Cecilie Schirmer2, Jahn Martin Nesland10 and Bjørn Naume11*

Author affiliations

1 Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

2 Department of Pathology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

3 Department of Oncology, Oslo University Hospital, Ullevål, Oslo, Norway

4 Department of Surgery, Oslo University Hospital, Ullevål, Oslo, Norway

5 Department of Oncology, Sykehuset Innlandet, Gjøvik, Norway

6 Department of Oncology, University Hospital Northern Norway, Tromsø, Norway and Department of Clinical Medicine, University of Tromsø, Tromsø, Norway

7 Department of Oncology, Sørlandet Hospital, Kristiansand, Norway

8 Department of Oncology, Stavanger University Hospital, Stavanger, Norway

9 Department of Oncology, Ålesund Hospital, Ålesund, Norway

10 Department of Pathology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway and Institute of Clinical Medicine, University of Oslo, Oslo, Norway

11 Department of Oncology, Oslo University Hospital, Oslo, Norway and K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway

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Citation and License

BMC Cancer 2012, 12:616  doi:10.1186/1471-2407-12-616

Published: 22 December 2012

Abstract

Background

Presence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response.

Methods

A total of 1121 patients with pN1-3 or pT1c/T2G2-3pN0-status were enrolled. All had completed primary surgery and received 6 cycles of anthracycline-containing chemotherapy. BM-aspiration was performed 8-12 weeks after chemotherapy (BM1), followed by a second BM-aspiration 6 months later (BM2). DTC-status was determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. If DTCs were present at BM2, docetaxel (100 mg/m2, 3qw, 6 courses) was administered, followed by DTC-analysis 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion.

Results

Clinical follow-up (FU) is still ongoing. Here, the descriptive data from the study are presented. Of 1085 patients with a reported DTC result at both BM1 and BM2, 94 patients (8.7%) were BM1 positive and 83 (7.6%) were BM2 positive. The concordance between BM1 and BM2 was 86.5%. Both at BM1 and BM2 DTC-status was significantly associated with lobular carcinomas (p = 0.02 and p = 0.03, respectively; chi-square). In addition, DTC-status at BM2 was also associated with pN-status (p = 0.009) and pT-status (p = 0.03). At BM1 28.8% and 12.8% of the DTC-positive patients had ≥2 DTCs and ≥3 DTCs, respectively. At BM2, the corresponding frequencies were 47.0% and 25.3%. Of 72 docetaxel-treated patients analyzed at BM3 and/or BM4, only 15 (20.8%) had persistent DTCs. Of 17 patients with ≥3 DTCs before docetaxel treatment, 12 patients turned negative after treatment (70.6%). The change to DTC-negativity was associated with the presence of ductal carcinoma (p = 0.009).

Conclusions

After docetaxel treatment, the majority of patients experienced disappearance of DTCs. As this is not a randomized trial, the results can be due to effects of adjuvant (docetaxel/endocrine/trastuzumab) treatment and/or limitations of the methodology. The clinical significance of these results awaits mature FU data, but indicates a possibility for clinical use of DTC-status as a residual disease-monitoring tool and as a surrogate marker of treatment response.

Trial registration

Clin Trials Gov NCT00248703