Annals of Surgical Oncology

, Volume 23, Issue 3, pp 757–766 | Cite as

Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: Prognostic Impact in Immunophenotypic Subgroups and Clinical Implication for Bisphosphonate Treatment

  • Stefan Stefanovic
  • Ingo Diel
  • Peter Sinn
  • Stefan Englert
  • Andre Hennigs
  • Christine Mayer
  • Sarah Schott
  • Markus Wallwiener
  • Maria Blumenstein
  • Michael Golatta
  • Joerg Heil
  • Joachim Rom
  • Christof Sohn
  • Andreas Schneeweiss
  • Florian Schuetz
  • Christoph Domschke
Breast Oncology



Disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (BC) patients are a promising surrogate marker of micrometastatic spread and an independent predictor of poor prognosis for disease-free survival (DFS) and overall survival (OS). The present study aims to analyze DTCs as an independent prognostic factor for DFS/OS in tumor biology and bisphosphonate treatment.


A total of 504 patients with operable primary BC and a median observation time of 72.3 months [lower quartile (LQ) 58.1; upper quartile (UQ) 82.8] have been included. DTCs were detected via immunohistochemistry as MUC-1 positive cells in the BM of 59.13 % (298 of 504) of the patients. The immunophenotyping of cancer cells was achieved immunohistochemically as well.


For luminal A/B carcinoma patients, we observed a significant benefit of BM DTC negativity with respect to DFS (luminal A, P = 0.0498; luminal B, P = 0.0224). In triple-negative patients, DTC-negative BM was associated with a longer OS (P = 0.0326). In a multivariate Cox survival analysis relating to DFS and OS, the DTC status was identified as an independent prognostic factor for DFS in luminal A/B BC (P = 0.0071). A multivariate Cox survival analysis among DTC-positive patients with luminal immunophenotype showed bisphosphonate application (P = 0.0326) to be an independent prognostic factor for DFS.


The findings of our multivariate analyses reveal BM DTC positivity as an independent risk factor for DFS particularly in luminal A/B BC patients. This might be a novel criterion for the identification of candidates most likely to benefit from additional adjuvant therapy possibly including bisphosphonates.


Breast Cancer Overall Survival Bisphosphonate Treatment Disseminate Tumor Cell Primary Breast Cancer Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





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Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Stefan Stefanovic
    • 1
  • Ingo Diel
    • 2
  • Peter Sinn
    • 3
  • Stefan Englert
    • 4
  • Andre Hennigs
    • 1
  • Christine Mayer
    • 1
  • Sarah Schott
    • 1
  • Markus Wallwiener
    • 1
  • Maria Blumenstein
    • 1
  • Michael Golatta
    • 1
  • Joerg Heil
    • 1
  • Joachim Rom
    • 1
  • Christof Sohn
    • 1
  • Andreas Schneeweiss
    • 1
  • Florian Schuetz
    • 1
  • Christoph Domschke
    • 1
  1. 1.Breast Unit, Department of Gynecology and ObstetricsHeidelberg University HospitalHeidelbergGermany
  2. 2.CGG-Clinic MannheimMannheimGermany
  3. 3.Department of PathologyHeidelberg University HospitalHeidelbergGermany
  4. 4.Institute of Medical Biometry and InformaticsHeidelberg University HospitalHeidelbergGermany

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