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Detection and clinical relevance of hematogenous tumor cell dissemination in patients with ductal carcinoma in situ

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Abstract

Hematogenous tumor cell dissemination is a crucial step in systemic disease progression and predicts reduced clinical outcome in breast cancer patients. Only invasive cancers are assumed to shed tumor cells into the bloodstream and infiltrate lymph nodes. However, recent studies revealed that disseminated tumor cells (DTCs) may be detected in bone marrow (BM) of patients with preinvasive lesions, i.e., ductal carcinoma in situ (DCIS). The purpose of this analysis was to examine the incidence and clinical value of DTC detection in a large series of patients with pure DCIS. 404 patients treated for DCIS at the University Hospital Tuebingen, Germany were included into this analysis. BM was analyzed by immunocytochemistry (pancytokeratin antibody A45-B/B3) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Sentinel nodes were analyzed in 316 patients by step sectioning and hematoxylin–eosin staining. DTCs were detected in 63 of 404 patients (16 %). No correlation was observed between BM status and tumor size, grading, histology or Van Nuys prognostic index. In two cases, metastatic spread into lymph nodes was observed; isolated tumor cells were found in one patient. After a median follow-up of 45 months (range 3–131 months), 3 % of BM positive patients died compared to 1 % of BM negative patients (p = 0.254). Relapse of any kind was observed in 7 % of patients with DTCs vs. 5 % of patients without DTCs (p = 0.644). The differences in overall (p = 0.088) and disease-free survival (p = 0.982) calculated by log-rank test were not statistically significant. Tumor cell dissemination may be detected in patients diagnosed with DCIS. Whether these cells disseminate from real preinvasive mammary lesions or represent the earliest step of microinvasion, remains unclear. A longer follow-up may be necessary to accurately assess clinical value of these cells in DCIS patients.

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Abbreviations

ADH:

Atypical ductal hyperplasia

BM:

Bone marrow

CK:

Cytokeratin

CTC:

Circulating tumor cell(s)

DIN:

Ductal intraepithelial neoplasia

DCIS:

Ductal carcinoma in situ

DTC:

Disseminated tumor cell(s)

HE:

Hematoxylin–eosin

ITC:

Isolated tumor cell

SN:

Sentinel node

SLNB:

Sentinel lymph node biopsy

VNPI:

Van Nuys prognostic index

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Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany

    Malgorzata Banys, Natalia Krawczyk & Tanja Fehm

  2. Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany

    Markus Hahn, Ines Gruber, Andreas Hartkopf, Florin-Andrei Taran, Carmen Röhm & Diethelm Wallwiener

  3. Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany

    Markus Wallwiener

  4. Department of Pathology, University of Tuebingen, Tuebingen, Germany

    Ralf Kurth & Annette Staebler

  5. Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg, Germany

    Malgorzata Banys

  6. Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt, Germany

    Sven Becker

  7. Department of Obstetrics and Gynecology, University of Saarland, Homburg/Saar, Germany

    Erich-Franz Solomayer

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  1. Malgorzata Banys
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  11. Erich-Franz Solomayer
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  12. Diethelm Wallwiener
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  13. Annette Staebler
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  14. Tanja Fehm
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Correspondence to Malgorzata Banys.

Additional information

M. Banys and M. Hahn contributed equally to this work.

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Banys, M., Hahn, M., Gruber, I. et al. Detection and clinical relevance of hematogenous tumor cell dissemination in patients with ductal carcinoma in situ. Breast Cancer Res Treat 144, 531–538 (2014). https://doi.org/10.1007/s10549-014-2898-6

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  • DOI: https://doi.org/10.1007/s10549-014-2898-6

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