Research article

ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients

Tanja Fehm¹ , Natalia Krawczyk¹ , Erich-Franz Solomayer¹ , Graziella Becker-Pergola¹ , Silke Dürr-Störzer¹ , Hans Neubauer¹ , Harald Seeger¹ , Annette Staebler² , Diethelm Wallwiener¹ and Sven Becker¹

¹  Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse 7, D-72076 Tuebingen, Germany

²  Department of Pathology, University of Tuebingen, Liebermeisterstrasse 8, D-72076 Tuebingen, Germany

author email corresponding author email

Breast Cancer Research 2008, 10:R76doi:10.1186/bcr2143

Published:	15 September 2008

See related editorial by Gebauer, http://breast-cancer-research.com/content/10/5/112

Abstract

Introduction

Isolated disseminated tumour cells (DTC) are regarded as surrogate markers for minimal residual disease in breast cancer. Characterisation of these cells could help understand the known limitations of adjuvant therapy. Of particular interest is their oestrogen-receptor (ER) status because endocrine adjuvant therapy remains a cornerstone of breast cancer treatment.

Methods

Bone marrow (BM) aspirates from 254 patients with primary breast cancer were included in this study. A double immunofluorescence staining procedure was established for the identification of cytokeratin (CK) positive/Erα-positive cells. ERα status of the primary tumour was assessed immunohistochemically using the same antibody against ERα.

Results

In 107 of 254 (42%) breast cancer patients, CK-positive cells could be detected in the BM. More than one DTC in the BM was observed in 38 of the 107 patients. The number of detected cells ranged between 1 and 55 cells per 2 × 10⁶ mononuclear cells. DTCs demonstrated ERα positivity in 12% of the patients. The ERα expression was heterogeneous in 10 of the 38 (26%) patients with more than one DTC. The concordance rate of ERα status between primary tumour and DTC was 28%. Only 12 of 88 patients with ERα-positive tumours also had ERα-positive DTCs.

Conclusions

Primary tumours and DTCs displayed a concordant ERα status in only 28% of cases. Most of the DTCs were ERα negative despite the presence of an ERα-positive primary tumour. These findings further underline the distinct nature of DTCs and may explain the failure rates seen in conventional endocrine adjuvant therapy.