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Open Access Research article

Persistent tumor cells in bone marrow of non-metastatic breast cancer patients after primary surgery are associated with inferior outcome

Kjersti Tjensvoll1, Satu Oltedal1, Reino Heikkilä16, Jan Terje Kvaløy23, Bjørnar Gilje1, James M Reuben4, Rune Smaaland1 and Oddmund Nordgård15*

  • * Corresponding author: Oddmund Nordgård nood@sus.no

Author affiliations

1 Department of Haematology and Oncology, Stavanger University Hospital, N-4068, Stavanger, Norway

2 Department of Mathematics and Natural Sciences, University of Stavanger, N-4036, Stavanger, Norway

3 Division of Research and Human Resources, Stavanger University Hospital, N-4068, Stavanger, Norway

4 Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

5 Laboratory for Molecular Biology, Department of Haematology and Oncology, Stavanger University Hospital, N-4068, Stavanger, Norway

6 Present address: Roche Norge AS, 0915, Oslo, Norway

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Citation and License

BMC Cancer 2012, 12:190  doi:10.1186/1471-2407-12-190

Published: 28 May 2012

Abstract

Background

To investigate the prognostic significance of disseminated tumor cells (DTCs) in bone marrow (BM) from non-metastatic breast cancer patients before and after surgery.

Methods

Patients with non-metastatic breast cancer were consecutively recruited to this project during the years 1998–2000. Real-time RT-PCR quantification of a DTC multimarker panel consisting of cytokeratin 19, mammaglobin A and TWIST1 mRNA was performed in BM samples obtained from 154 patients three weeks (BM2) and/or six months after surgery (BM3). The results were compared to previously published data from pre-operative BM analyses for the same patients.

Results

DTCs were identified in post-operative BM samples (BM2 and/or BM3) from 23 (15%) of the 154 patients investigated. During a median follow-up of 98 months, 10 (44%) of these patients experienced systemic relapse as compared to 16 (12%) of 131 DTC-negative patients. Kaplan-Meier estimates of systemic recurrence-free- and breast-cancer specific survival demonstrated significantly shorter survival for patients with persistent DTCs in BM after surgery (p≤0.001). By multivariate Cox regression analyses, persistent DTCs after surgery was an independent predictor of both systemic recurrence-free- (HR = 5.4, p < 0.001) and breast-cancer specific survival (HR = 5.3, p < 0.001). Furthermore, the prognostic value of DTCs in BM was similar for pre- and post surgery samples. However, patients with DTCs both before and after surgery (BM1 and BM2/3) had a particularly poor prognosis (systemic recurrence-free survival: HR = 7.2, p < 0.0001 and breast-cancer specific survival: HR = 8.0, p < 0.0001).

Conclusions

Detection of persistent DTCs in BM samples obtained after surgery identified non-metastatic breast cancer patients at high risk for systemic relapse, and with reduced breast-cancer specific survival. Furthermore, patients with positive DTC status both before and after surgery had a particularly poor prognosis.

Keywords:
Breast cancer; Minimal residual disease; Multimarker real-time PCR; Bone marrow; DTC; prognosis