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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

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors and Affiliations

  1. Breast Unit, Department of Gynecology and Obstetrics, Heidelberg University Hospital, Heidelberg, Germany

    Stefan Stefanovic MD, Andre Hennigs MD, Christine Mayer MD, Sarah Schott MD, Markus Wallwiener MD, Maria Blumenstein MD, Michael Golatta MD, Joerg Heil MD, Joachim Rom MD, Christof Sohn MD, Andreas Schneeweiss MD, Florian Schuetz MD & Christoph Domschke MD

  2. CGG-Clinic Mannheim, Mannheim, Germany

    Ingo Diel MD

  3. Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany

    Peter Sinn MD

  4. Institute of Medical Biometry and Informatics, Heidelberg University Hospital, Heidelberg, Germany

    Stefan Englert PhD

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  1. Stefan Stefanovic MD
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Stefanovic, S., Diel, I., Sinn, P. et al. 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. Ann Surg Oncol 23, 757–766 (2016). https://doi.org/10.1245/s10434-015-4895-3

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