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Mitotic activity and bone marrow micrometastases have independent prognostic value in node positive breast cancer patients

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Abstract

The purpose of this article is to investigate the prognostic value of the mitotic activity index (MAI) and the presence of disseminated tumor cells (DTCs) in bone marrow (BM), in clinically operable breast cancer patients. We compared routinely assessed MAI, classic prognosticators and BM DTCs, detected by a real-time RT-PCR multimarker assay including cytokeratin 19, mammaglobin A and TWIST1 mRNA, in 179 consecutive patients with operable breast cancer. Over a median follow-up of 96 months (range: 1–126 months), 31 (17.3%) patients experienced a systemic relapse and 26 (14.5%) died of breast cancer-related causes. MAI (≥ 10) was strongly associated with breast cancer-related death in lymph node (LN)-negative patients (hazard ratio (HR): 7.0, confidence interval (CI) 1.74–27.9), whereas both BM DTC-status (HR: 3.3, CI 1.25–8.52) and MAI (HR: 3.1, CI 1.08–8.8) were significant in LN-positive patients. With multivariate Cox regression, MAI was the only significant predictor of breast cancer-specific survival (HR 7.0, CI 1.7–27.9) in LN-negative patients. In LN-positive patients, both BM DTC-status and MAI were strong independent predictors of breast cancer-specific survival (HR 3.3, CI 1.25-8.49 and HR 3.1, CI 1.1–8.9), respectively. Where, however, MAI and BM DTC-status as single parameters were replaced by a combination of these, this showed to be the most significant prognostic marker in both LN-negative (HR 7.7, CI 1.2-50) and LN-positive (HR 6.0, CI 1.4 to 26.4) patients with regard to breast cancer-specific survival. A combination of MAI and BM DTC detection identified both LN-negative and LN-positive breast cancer patients with poor prognosis.

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Acknowledgments

This study was supported by the Norwegian Regional Health Collaboration of Health West, the Norwegian Cancer Society and Stavanger University Hospital.

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Authors and Affiliations

  1. Department of Haematology and Oncology, Stavanger University Hospital, Stavanger, Norway

    Bjørnar Gilje, Oddmund Nordgård, Kjersti Tjensvoll & Rune Smaaland

  2. Department of Pathology, Stavanger University Hospital, Stavanger, Norway

    Emiel A. M. Janssen & Jan P. A. Baak

  3. Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway

    Oddmund Nordgård, Kjersti Tjensvoll & Rune Smaaland

  4. The Gade Institute, University of Bergen, Bergen, Norway

    Jan P. A. Baak

  5. Department of Surgery, Stavanger University Hospital, Stavanger, Norway

    Håvard Søiland

  6. Institute of Medicine, University of Bergen, 5021, Bergen, Norway

    Rune Smaaland

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  1. Bjørnar Gilje
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Correspondence to Jan P. A. Baak.

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Gilje, B., Nordgård, O., Tjensvoll, K. et al. Mitotic activity and bone marrow micrometastases have independent prognostic value in node positive breast cancer patients. Breast Cancer Res Treat 128, 137–146 (2011). https://doi.org/10.1007/s10549-011-1487-1

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  • DOI: https://doi.org/10.1007/s10549-011-1487-1

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