ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients.
BACKGROUND
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/Eralpha-positive cells. ERalpha status of the primary tumour was assessed immunohistochemically using the same antibody against ERalpha.


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 x 10(6) mononuclear cells. DTCs demonstrated ERalpha positivity in 12% of the patients. The ERalpha expression was heterogeneous in 10 of the 38 (26%) patients with more than one DTC. The concordance rate of ERalpha status between primary tumour and DTC was 28%. Only 12 of 88 patients with ERalpha-positive tumours also had ERalpha-positive DTCs.


CONCLUSIONS
Primary tumours and DTCs displayed a concordant ERalpha status in only 28% of cases. Most of the DTCs were ERalpha negative despite the presence of an ERalpha-positive primary tumour. These findings further underline the distinct nature of DTCs and may explain the failure rates seen in conventional endocrine adjuvant therapy.
Fehm
Tanja
T
Department of Obstetrics and Gynecology, University of Tuebingen, Germany. tanja.fehm@t-online.de
Krawczyk
Natalia
N
Solomayer
Erich-Franz
EF
Becker-Pergola
Graziella
G
Dürr-Störzer
Silke
S
Neubauer
Hans
H
Seeger
Harald
H
Staebler
Annette
A
Wallwiener
Diethelm
D
Becker
Sven
S
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D002277:Carcinoma / Q000737:chemistry / Q000188:drug therapy / Q000556:secondary*; D045744:Cell Line, Tumor / Q000737:chemistry; D017024:Chemotherapy, Adjuvant; D004847:Epithelial Cells / Q000737:chemistry*; D047628:Estrogen Receptor alpha / Q000032:analysis*; D004967:Estrogens; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007633:Keratins / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D018365:Neoplasm, Residual; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*
D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D004967:Estrogens; D009363:Neoplasm Proteins; D007633:Keratins
Breast Cancer Res Treat. 2006 May;97(1):91-6
16319975
N Engl J Med. 2000 Feb 24;342(8):525-33
10684910
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17361-5
17079488
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
12629218
J Natl Cancer Inst. 1993 Sep 1;85(17):1419-24
7688814
Cytotherapy. 1999;1(5):377-88
20426539
N Engl J Med. 2005 Aug 25;353(8):793-802
16120859
Steroids. 2001 Dec;66(12):905-10
11711119
J R Soc Med. 1982 Sep;75(9):719-22
7120257
N Engl J Med. 2005 Dec 29;353(26):2747-57
16382061
Nature. 2001 Nov 1;414(6859):105-11
11689955
Int J Cancer. 1998 Mar 2;75(5):750-6
9495244
J Clin Oncol. 2000 Jan;18(1):80-6
10623696
Cancer. 1985 Feb 1;55(3):546-51
3965108
Clin Cancer Res. 2001 Dec;7(12):4102-8
11751508
Trends Endocrinol Metab. 2004 Jul;15(5):193-7
15223047
Cancer Lett. 1980 Dec;11(2):81-7
6450636
Breast Cancer Res Treat. 2005 Mar;90(1):65-70
15770528
J Surg Oncol. 1994 Oct;57(2):71-7
7934066
Cancer. 2006 Sep 1;107(5):885-92
16874814
Lancet. 2002 Aug 31;360(9334):683-9
12241875
Cancer Res. 1991 Sep 1;51(17):4712-5
1873815
Cancer Res. 1990 Feb 1;50(3):717-21
2297709
J Natl Cancer Inst. 2006 Jul 19;98(14):1011-4
16849684
Clin Cancer Res. 2004 Aug 15;10(16):5342-8
15328170
Eur J Cancer Clin Oncol. 1984 Aug;20(8):1011-8
6540683
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7737-42
12808139
Clin Cancer Res. 2006 Oct 1;12(19):5615-21
17020963
Breast Cancer Res Treat. 2006 Jul;98(2):179-84
16552629
J Clin Oncol. 1996 Sep;14(9):2584-9
8823339
Recent Results Cancer Res. 2003;162:141-7
12790328
Anticancer Res. 2005 May-Jun;25(3B):2171-5
16158960
Clin Exp Metastasis. 1999 Jun;17(4):325-32
10545019
J Natl Cancer Inst. 1996 Nov 20;88(22):1652-8
8931609
Clin Cancer Res. 2005 Feb 1;11(3):1154-9
15709183
J Cell Physiol. 1992 Mar;150(3):534-44
1537883