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01-10-2009 | Preclinical Study

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Authors: Stella Apostolaki, Maria Perraki, Galatea Kallergi, Maria Kafousi, Savvas Papadopoulos, Athanasios Kotsakis, Athanasios Pallis, Nikolaos Xenidis, Lyda Kalmanti, Kostas Kalbakis, Sofia Agelaki, Antonia Kalykaki, Christos Stournaras, Efstathios Stathopoulos, Vassilis Georgoulias, Dimitris Mavroudis

Published in: Breast Cancer Research and Treatment | Issue 3/2009

Abstract

To evaluate whether HER2 mRNA could be used as a marker of circulating tumor cells (CTCs) in women with operable breast cancer. A nested RT-PCR assay was developed and used for the detection of HER2 mRNA-positive CTCs. Blood from 216 women with early breast cancer obtained before adjuvant treatment was tested for HER2 mRNA-positive cells to assess their prognostic value. Nested RT-PCR for HER2 mRNA showed high sensitivity whereas no HER2 mRNA-positive cells could be identified in the blood of healthy donors. HER2 mRNA-positive CTCs were detected in 53 (24.5%) of 216 patients and HER2 mRNA detection was associated with reduced disease-free survival (DFS; P < 0.0001) and overall survival (OS; P = 0.004). In multivariate analysis, detection of HER2 mRNA-positive CTCs emerged as independent prognostic factor for DFS (P = 0.0001) and OS (P = 0.003). HER2 mRNA could be a valuable prognostic marker for the detection of CTCs in early breast cancer patients.

Pantel K, Cote RJ, Fodstad O (1999) Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst 91:1113–1124. doi:10.1093/jnci/91.13.1113 PubMedCrossRef

Braun S, Pantel K, Muller P et al (2000) Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II or III breast cancer. N Engl J Med 342:525–533. doi:10.1056/NEJM200002243420801 PubMedCrossRef

Diel IJ, Kaufmann M, Costa SD et al (1996) Micrometastatic breast cancer cells in bone marrow at primary surgery: Prognostic value in comparison with nodal status. J Natl Cancer Inst 88:1652–1658. doi:10.1093/jnci/88.22.1652 PubMedCrossRef

Mansi JL, Easton D, Berger U et al (1991) Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years’ follow-up. Eur J Cancer 27:1552–1555PubMedCrossRef

Stathopoulou A, Vlachonikolis I, Mavroudis D et al (2002) 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 20:3404–3412. doi:10.1200/JCO.2002.08.135 PubMedCrossRef

Xenidis N, Perraki M, Kafousi M et al (2006) Predictive and prognostic value of peripheral blood cytokeratic-19 mRNA positive cells detected by real time PCR in node-negative breast cancer patients. J Clin Oncol 24:3756–3762. doi:10.1200/JCO.2005.04.5948 PubMedCrossRef

Braun S, Vogl FD, Naume B et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802. doi:10.1056/NEJMoa050434 PubMedCrossRef

Zach O, Kasparu H, Krieger O et al (1999) Detection of circulating mammary carcinoma cells in the peripheral blood of breast cancer patients via a nested reverse transcriptase polymerase chain reaction assay for mammaglobin mRNA. J Clin Oncol 17:2015–2019PubMed

Luppi M, Morselli M, Bandieri E et al (1996) Sensitive detection of circulating breast cancer cells by reverse-transcriptase polymerase chain reaction of maspin gene. Ann Oncol 7:619–624PubMed

10.

Gerhard M, Juhl H, Kalthoff H et al (1994) Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction. J Clin Oncol 12:725–729PubMed

11.

Stathopoulou A, Mavroudis D, Perraki M et al (2003) Molecular detection of cancer cells in the peripheral blood of patients with breast cancer: Comparison of CK-19, CEA and maspin as detection markers. Anticancer Res 23:1883–1890PubMed

12.

Brandt B, Roetger A, Heidl S et al (1998) Isolation of blood-bored epithelium-derived c-erb-B2 oncoprotein-positive clustered cells from the peripheral blood of breast cancer patients. Int J Cancer 76:824–828. doi:10.1002/(SICI)1097-0215(19980610)76:6<824::AID-IJC10>3.0.CO;2-2PubMedCrossRef

13.

Solomayer EF, Becker S, Pergolo-Becker G et al (2006) Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients. Breast Cancer Res Treat 98:179–184. doi:10.1007/s10549-005-9147-y PubMedCrossRef

14.

Braun S, Schlimok G, Heumos I et al (2001) erbB2 overexpression on occult tumor metastatic cells in bone marrow predicts poor clinical outcome of stage I-II breast cancer patients. Cancer Res 61:1890–1892PubMed

15.

Schechter AL, Stern DF, Vaidyanathan L et al (1984) The neu oncogene: an erb-B-related gene encoding a 185000-Mr tumour antigen. Nature 312:513–516. doi:10.1038/312513a0 PubMedCrossRef

16.

Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 235:177–182. doi:10.1126/science.3798106 PubMedCrossRef

17.

Slamon DJ, Godolphin W, Jones LA et al (1989) Studies of the HER-2/neu proto oncogene in human breast cancer and ovarian cancer. Science 244:707–712. doi:10.1126/science.2470152 PubMedCrossRef

18.

Toikkanen S, Helin H, Isola J et al (1992) Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. J Clin Oncol 10:1044–1048PubMed

19.

Wulfing P, Brochard J, Buerger H et al (2006) HER 2 positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12:1715–1720. doi:10.1158/1078-0432.CCR-05-2087 PubMedCrossRef

20.

Wasserman L, Dreilinger A, Easter D et al (1999) A seminested RT-PCR assay for HER2/neu: initial validation of a new method for the detection of disseminated breast cancer cells. Mol Diagn 4:21–28. doi:10.1016/S1084-8592(99)80046-0 PubMedCrossRef

21.

Thomas DG, Giordano TJ, Sanders D et al (2002) Absence of Her2/neu gene expression in osteosarcoma and skeletal Ewing’s sarcoma. Clin Cancer Res 8:788–793PubMed

22.

Bozionellou V, Mavroudis D, Perraki M et al (2004) Trastuzumab administration can effectively target chemotherapy-resistant cytokeratin-19 messenger RNA-positive tumor cells in the peripheral blood and bone marrow of patients with breast cancer. Clin Cancer Res 10:8185–8194. doi:10.1158/1078-0432.CCR-03-0094 PubMedCrossRef

23.

Armitage P, Berry G (1994) Statistical methods in medical research, 3rd edn. Blackwell Scientific, Oxford

24.

Stathopoulou A, Gizi A, Perraki M et al (2003) Real-time quantification of CK-19 mRNA positive cells in peripheral blood of breast cancer patients using the LightCycler system. Clin Cancer Res 9:5145–5151PubMed

25.

Muller P, Weckermann D, Riethmuller G et al (1996) Detection of genetic alterations in micrometastatic cells in bone marrow of cancer patients with fluorescence in situ hybridization. Cancer Genet Cytogenet 88:8–16. doi:10.1016/0165-4608(95)00189-1 PubMedCrossRef

26.

Meng S, Tripathy D, Shete S et al (2004) HER2 gene amplification can be aquired as breast cancer progresses. Proc Natl Acad Sci USA 101:9393–9398. doi:10.1073/pnas.0402993101 PubMedCrossRef

27.

Zidan J, Dashkovsky I, Stayerman C et al (2005) Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 93:552–556. doi:10.1038/sj.bjc.6602738 PubMedCrossRef

28.

Apostolaki S, Perraki M, Pallis A et al (2007) Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance. Ann Oncol 18:851–858. doi:10.1093/annonc/mdl502 PubMedCrossRef

29.

Braun S, Kentenich C, Janni W et al (2000) Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in the bone marrow of high-risk breast cancer patients. J Clin Oncol 18:80–86PubMed

30.

Xenidis N, Vlachonikolis I, Mavroudis D et al (2003) Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer. Ann Oncol 14:849–855. doi:10.1093/annonc/mdg259 PubMedCrossRef

Title: Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance
Authors: Stella Apostolaki
Maria Perraki
Galatea Kallergi
Maria Kafousi
Savvas Papadopoulos
Athanasios Kotsakis
Athanasios Pallis
Nikolaos Xenidis
Lyda Kalmanti
Kostas Kalbakis
Sofia Agelaki
Antonia Kalykaki
Christos Stournaras
Efstathios Stathopoulos
Vassilis Georgoulias
Dimitris Mavroudis
Publication date: 01-10-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0239-3

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