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PMID: 19664291 Published · ppublish English Comparative Study Journal Article

Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells.

Breast cancer research : BCR ·Vol. 11 ·No. 4 ·2009-00-00 ·Pages R59

Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D, Kimmig R, Kasimir-Bauer S

Abstract

The role of circulating tumor cells (CTCs) in blood of primary breast cancer patients is still under investigation. We evaluated the incidence of CTCs in blood, we evaluated the correlation between CTCs and disseminated tumor cells (DTCs) in the bone marrow (BM), and we characterized CTCs for the expression of HER2, the estrogen receptor (ER) and the progesterone receptor (PR). Blood of 431 patients with primary breast cancer were analyzed for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer (AdnaGen AG, Germany). Expression of the ER and PR was assessed in an additional RT-PCR. BM aspirates from 414 patients were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. DTCs were found in 107/414 patients (24%), CTCs were detected in 58/431 (13%) patients. DTCs were associated with PR status of the primary tumor (P = 0.04) and CTCs significantly correlated with nodal status (P = 0.04), ER (P = 0.05), and PR (P = 0.01). DTCs in the BM weakly correlated with CTCs (P = 0.05) in blood. Interestingly, the spread of CTCs was mostly found in triple-negative tumors (P = 0.01) and CTCs in general were mostly found to be triple-negative regardless of the ER, PR and HER2 status of the primary tumor. (1) Due to the weak concordance between CTCs and DTCs the clinical relevance may be different. (2) The biology of the primary tumor seems to direct the spread of CTCs. (3) Since the expression profile between CTCs and the primary tumor differs, the consequence for the selection of adjuvant treatment has to be evaluated.

MeSH Terms
Adenocarcinoma/blood,pathology Antigens, Neoplasm/analysis Biomarkers, Tumor/analysis Bone Marrow/pathology Bone Marrow Neoplasms/secondary,ultrastructure Breast Neoplasms/blood,chemistry,drug therapy,pathology Cell Adhesion Molecules/analysis Chemotherapy, Adjuvant Epithelial Cell Adhesion Molecule Estrogens Female Humans Keratins/analysis Mucin-1/analysis Neoplasm Proteins/analysis Neoplasm, Residual Neoplasms, Hormone-Dependent/blood,chemistry,pathology Neoplastic Cells, Circulating/chemistry Neoplastic Stem Cells/chemistry Progesterone Receptor, ErbB-2/analysis Receptors, Estrogen/analysis Receptors, Progesterone/analysis Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Antigens, Neoplasm Biomarkers, Tumor Cell Adhesion Molecules EPCAM protein, human Epithelial Cell Adhesion Molecule Estrogens MUC1 protein, human Mucin-1 Neoplasm Proteins Receptors, Estrogen Receptors, Progesterone Progesterone Keratins ERBB2 protein, human Receptor, ErbB-2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fehm Tanja
Department of Gynecology and Obstetrics, Calwer Strasse 7, University Hospital of Tuebingen, D-72076 Tuebingen, Germany. tanja.fehm@med.uni-tuebingen.de
Hoffmann Oliver
Aktas Bahriye
Becker Sven
Solomayer Erich F
Wallwiener Diethelm
Kimmig Rainer
Kasimir-Bauer Sabine
References (57)
57 references, click to expand
  1. Comparison of the clinical significance of occult tumor cells in blood and bone marrow in breast cancer.
    Int J Cancer. 2006 Apr 15;118(8):2013-9 PMID: 16287086
  2. Evaluation of a RT-PCR based routine screening tool for the detection of disseminated epithelial cells in the bone marrow of breast cancer patients.
    Breast Cancer Res Treat. 2009 Sep;117(2):227-33 PMID: 18791864
  3. A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation.
    Cancer. 2006 Sep 1;107(5):885-92 PMID: 16874814
  4. HER-2 testing in breast cancer using immunohistochemical analysis and fluorescence in situ hybridization: a single-institution experience of 2,279 cases and comparison of dual-color and single-color scoring.
    Am J Clin Pathol. 2004 May;121(5):631-6 PMID: 15151202
  5. Micrometastatic disease in breast cancer: clinical implications.
    Eur J Cancer. 2008 Dec;44(18):2726-36 PMID: 19056036
  6. The clinical significance of circulating tumour cells in breast cancer and colorectal cancer patients.
    Anticancer Res. 2007 May-Jun;27(3A):1337-41 PMID: 17593628
  7. The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for keratin 19.
    Eur J Cancer. 1997 May;33(6):854-61 PMID: 9291805
  8. Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status.
    J Natl Cancer Inst. 1996 Nov 20;88(22):1652-8 PMID: 8931609
  9. Circulating tumor cells, disease progression, and survival in metastatic breast cancer.
    N Engl J Med. 2004 Aug 19;351(8):781-91 PMID: 15317891
  10. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients.
    J Clin Oncol. 2006 Aug 10;24(23):3756-62 PMID: 16769987
  11. Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies.
    Breast Cancer Res Treat. 2009 Jun;115(3):581-90 PMID: 18679793
  12. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer.
    J Clin Oncol. 2009 May 1;27(13):2177-84 PMID: 19332733
  13. Detection of cytokeratin-positive cells in the bone marrow of breast cancer patients undergoing adjuvant therapy.
    Breast Cancer Res Treat. 2006 May;97(1):91-6 PMID: 16319975
  14. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity.
    Clin Cancer Res. 2005 May 15;11(10):3678-85 PMID: 15897564
  15. Persistent evidence of circulating tumor cells detected by means of RT-PCR for CEA mRNA predicts early relapse: a prospective study in node-negative breast cancer.
    Surgery. 2004 Apr;135(4):419-26 PMID: 15041966
  16. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer.
    N Engl J Med. 2000 Feb 24;342(8):525-33 PMID: 10684910
  17. ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients.
    Cancer Res. 2001 Mar 1;61(5):1890-5 PMID: 11280743
  18. Circulating tumor cells in metastatic breast cancer: biologic staging beyond tumor burden.
    Clin Breast Cancer. 2007 Feb;7(6):471-9 PMID: 17386124
  19. Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis.
    Int J Cancer. 2003 Dec 20;107(6):984-90 PMID: 14601059
  20. Time independence of the prognostic impact of tumor cell detection in the bone marrow of primary breast cancer patients.
    Clin Cancer Res. 2001 Dec;7(12):4102-8 PMID: 11751508
  21. Breast cancer, stem/progenitor cells and the estrogen receptor.
    Trends Endocrinol Metab. 2004 Jul;15(5):193-7 PMID: 15223047
  22. Real-time RT-PCR detection of disseminated tumour cells in bone marrow has superior prognostic significance in comparison with circulating tumour cells in patients with breast cancer.
    Br J Cancer. 2006 Mar 13;94(5):672-80 PMID: 16495933
  23. Prospective identification of tumorigenic breast cancer cells.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 PMID: 12629218
  24. Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells.
    J Natl Cancer Inst. 1993 Sep 1;85(17):1419-24 PMID: 7688814
  25. Combination of immunomagnetic enrichment with multiplex RT-PCR analysis for the detection of disseminated tumor cells.
    Anticancer Res. 2005 May-Jun;25(3A):1803-10 PMID: 16033103
  26. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry.
    Cancer. 2007 May 1;109(9):1721-8 PMID: 17387718
  27. Circulating tumor cells in breast cancer.
    Curr Opin Obstet Gynecol. 2008 Feb;20(1):55-60 PMID: 18197007
  28. Assessment of highly angiogenic and disseminated in the peripheral blood disease in breast cancer patients predicts for resistance to adjuvant chemotherapy and early relapse.
    Int J Cancer. 2004 Feb 10;108(4):620-7 PMID: 14696130
  29. Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. establishment of objective criteria for the evaluation of immunostained cells.
    Cytotherapy. 1999;1(5):377-88 PMID: 20426539
  30. Circulating tumor cells in patients with breast cancer dormancy.
    Clin Cancer Res. 2004 Dec 15;10(24):8152-62 PMID: 15623589
  31. A pooled analysis of bone marrow micrometastasis in breast cancer.
    N Engl J Med. 2005 Aug 25;353(8):793-802 PMID: 16120859
  32. Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status.
    Breast Cancer Res. 2007;9(5):R74 PMID: 17963511
  33. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance.
    J Clin Oncol. 2002 Aug 15;20(16):3404-12 PMID: 12177100
  34. Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells.
    Cancer Res. 1991 Sep 1;51(17):4712-5 PMID: 1873815
  35. Steroid hormone receptor status of mouse mammary stem cells.
    J Natl Cancer Inst. 2006 Jul 19;98(14):1011-4 PMID: 16849684
  36. Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse.
    Clin Cancer Res. 2008 Jun 1;14(11):3306-11 PMID: 18519757
  37. Isolated tumor cells in bone marrow three years after diagnosis in disease-free breast cancer patients predict unfavorable clinical outcome.
    Clin Cancer Res. 2004 Aug 15;10(16):5342-8 PMID: 15328170
  38. Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR.
    Breast Cancer Res Treat. 2009 Dec;118(3):455-68 PMID: 19115104
  39. Quantitative real-time RT-PCR of disseminated tumor cells in combination with immunomagnetic cell enrichment.
    Mol Biotechnol. 2006 Sep;34(1):15-27 PMID: 16943567
  40. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients.
    Clin Cancer Res. 2006 Mar 15;12(6):1715-20 PMID: 16551854
  41. ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients.
    Breast Cancer Res. 2008;10(5):R76 PMID: 18793387
  42. Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer.
    J Clin Oncol. 2007 Nov 20;25(33):5194-202 PMID: 17954712
  43. Circulating tumour cell detection: a direct comparison between the CellSearch System, the AdnaTest and CK-19/mammaglobin RT-PCR in patients with metastatic breast cancer.
    Br J Cancer. 2010 Jan 19;102(2):276-84 PMID: 19953098
  44. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype.
    Clin Cancer Res. 2006 Oct 1;12(19):5615-21 PMID: 17020963
  45. Estrogen receptor expression profile of disseminated epithelial tumor cells in bone marrow of breast cancer patients.
    Recent Results Cancer Res. 2003;162:141-7 PMID: 12790328
  46. Her2 expression on disseminated tumor cells from bone marrow of breast cancer patients.
    Anticancer Res. 2005 May-Jun;25(3B):2171-5 PMID: 16158960
  47. Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients.
    Breast Cancer Res Treat. 2006 Jul;98(2):179-84 PMID: 16552629
  48. Survival of tumor cells in stem cell preparations and bone marrow of patients with high-risk or metastatic breast cancer after receiving dose-intensive or high-dose chemotherapy.
    Clin Cancer Res. 2001 Jun;7(6):1582-9 PMID: 11410494
  49. Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients.
    Clin Cancer Res. 2004 Feb 15;10(4):1392-400 PMID: 14977842
  50. Stem cells, cancer, and cancer stem cells.
    Nature. 2001 Nov 1;414(6859):105-11 PMID: 11689955
  51. Breast cancer cell invasiveness: correlation with protein kinase C activity and differential regulation by phorbol ester in estrogen receptor-positive and -negative cells.
    Int J Cancer. 1998 Mar 2;75(5):750-6 PMID: 9495244
  52. Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications.
    Ann Oncol. 2005 Sep;16(9):1503-7 PMID: 15980160
  53. Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients.
    J Clin Oncol. 2000 Jan;18(1):80-6 PMID: 10623696
  54. Detection of tumour cells in the peripheral blood of patients with breast cancer. Development of a new sensitive and specific immunomolecular assay.
    J Exp Clin Cancer Res. 2004 Sep;23(3):465-8 PMID: 15595637
  55. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.
    JAMA. 2006 Jun 7;295(21):2492-502 PMID: 16757721
  56. Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis.
    Clin Cancer Res. 2005 Feb 1;11(3):1154-9 PMID: 15709183
  57. Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines.
    J Cell Physiol. 1992 Mar;150(3):534-44 PMID: 1537883
Article Info
Journal
Breast cancer research : BCR
Abbr.
Breast Cancer Res
ISSN
1465-542X
Published
2009-00-00
Epub
2009-00-10
Pages
R59
Language
English
Region
England
NLM ID
100927353
PMCID
PMC2750121
Subset
IM
Corrections
CommentIn
CommentIn
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