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

  • Bjørnar Gilje
  • Oddmund Nordgård
  • Kjersti Tjensvoll
  • Emiel A. M. Janssen
  • Håvard Søiland
  • Rune Smaaland
  • Jan P. A. Baak
Clinical Trial


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.


Breast cancer MAI DTC Proliferation Bone marrow 

Supplementary material

10549_2011_1487_MOESM1_ESM.ppt (192 kb)
Supplementary material 1 (PPT 190 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Bjørnar Gilje
    • 1
  • Oddmund Nordgård
    • 1
    • 3
  • Kjersti Tjensvoll
    • 1
    • 3
  • Emiel A. M. Janssen
    • 2
  • Håvard Søiland
    • 5
  • Rune Smaaland
    • 1
    • 3
    • 6
  • Jan P. A. Baak
    • 2
    • 4
  1. 1.Department of Haematology and OncologyStavanger University HospitalStavangerNorway
  2. 2.Department of PathologyStavanger University HospitalStavangerNorway
  3. 3.Laboratory for Molecular BiologyStavanger University HospitalStavangerNorway
  4. 4.The Gade InstituteUniversity of BergenBergenNorway
  5. 5.Department of SurgeryStavanger University HospitalStavangerNorway
  6. 6.Institute of MedicineUniversity of BergenBergenNorway

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