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Erschienen in: Breast Cancer Research and Treatment 3/2009

01.12.2009 | Clinical trial

Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

verfasst von: Marta Pestrin, Silvia Bessi, Francesca Galardi, Mara Truglia, Annibale Biggeri, Chiara Biagioni, Silvia Cappadona, Laura Biganzoli, Augusto Giannini, Angelo Di Leo

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2009

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Abstract

Biocharacterization of circulating tumor cells (CTCs) in the peripheral blood of advanced breast cancer (ABC) patients may represent a real-time tumor biopsy. We assessed HER2 status on CTCs from blood samples of ABC patients. CTCs were separated and stained using the CellSearch System®. HER2 status was assessed by immunofluorescence and, when technically feasible, by fluorescence in situ hybridization. Blood samples were obtained from 66 ABC patients. Forty patients had a positive CTC sample (61%) and of these, 15 (37%) had HER2 + CTCs. We found non-concordant results in 32% of cases: 29% (8/28) of HER2-negative primary tumors had HER2-positive CTCs and 42% (5/12) of HER2-positive primary tumors had HER2-negative CTCs (k = 0.278). Our study suggests that a subset of patients with HER2-negative primary tumors develops HER2-positive CTCs during disease progression.
Literatur
1.
Zurück zum Zitat Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904CrossRefPubMed Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904CrossRefPubMed
2.
Zurück zum Zitat Ring A, Smith IE, Dowsett M (2004) Circulating tumour cells in breast cancer. Lancet Oncol 5:79–88CrossRefPubMed Ring A, Smith IE, Dowsett M (2004) Circulating tumour cells in breast cancer. Lancet Oncol 5:79–88CrossRefPubMed
3.
Zurück zum Zitat Terstappen LW, Rao C, Gross S et al (2000) Peripheral blood tumor cell load reflects the clinical activity of the disease in patients with carcinoma of the breast. Int J Oncol 17:573–578PubMed Terstappen LW, Rao C, Gross S et al (2000) Peripheral blood tumor cell load reflects the clinical activity of the disease in patients with carcinoma of the breast. Int J Oncol 17:573–578PubMed
4.
Zurück zum Zitat Pachmann K, Camara O, Kavallaris A et al (2008) Monitoring the response of circulating epithelial tumor cells to adjuvant chemotherapy in breast cancer allows detection of patients at risk of early relapse. J Clin Oncol 10:1208–1215CrossRef Pachmann K, Camara O, Kavallaris A et al (2008) Monitoring the response of circulating epithelial tumor cells to adjuvant chemotherapy in breast cancer allows detection of patients at risk of early relapse. J Clin Oncol 10:1208–1215CrossRef
5.
Zurück zum Zitat Paterlini-Brechot P, Benali NL (2007) Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett 253:180–204CrossRefPubMed Paterlini-Brechot P, Benali NL (2007) Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett 253:180–204CrossRefPubMed
6.
Zurück zum Zitat Allard WJ, Matera J, Miller MC et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904CrossRefPubMed Allard WJ, Matera J, Miller MC et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904CrossRefPubMed
7.
Zurück zum Zitat Riethdorf S, Fritsche H, Müller V et al (2007) Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res 13:920–928CrossRefPubMed Riethdorf S, Fritsche H, Müller V et al (2007) Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res 13:920–928CrossRefPubMed
8.
Zurück zum Zitat McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23(36):9067–9072CrossRefPubMed McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23(36):9067–9072CrossRefPubMed
9.
Zurück zum Zitat Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791CrossRefPubMed Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791CrossRefPubMed
10.
Zurück zum Zitat Cristofanilli M, Hayes DF, Budd GT et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430CrossRefPubMed Cristofanilli M, Hayes DF, Budd GT et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430CrossRefPubMed
12.
Zurück zum Zitat Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127–137CrossRefPubMed Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127–137CrossRefPubMed
13.
Zurück zum Zitat 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 235:177–182CrossRefPubMed 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 235:177–182CrossRefPubMed
14.
Zurück zum Zitat Baselga J, Perez EA, Pienkowski T et al (2006) Adjuvant trastuzumab: a milestone in the treatment of HER2-positive early breast cancer. Oncologist 11:4–12CrossRefPubMed Baselga J, Perez EA, Pienkowski T et al (2006) Adjuvant trastuzumab: a milestone in the treatment of HER2-positive early breast cancer. Oncologist 11:4–12CrossRefPubMed
15.
Zurück zum Zitat Gonzalez-Angulo AM, Hortobágyi GN, Esteva FJ (2006) Adjuvant therapy with trastuzumab for HER2/neu-positive breast Cancer. The Oncologist 11:857–867CrossRefPubMed Gonzalez-Angulo AM, Hortobágyi GN, Esteva FJ (2006) Adjuvant therapy with trastuzumab for HER2/neu-positive breast Cancer. The Oncologist 11:857–867CrossRefPubMed
16.
Zurück zum Zitat Gancberg D, Di Leo A, Cardoso F et al (2002) Comparison of HER2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol 13:1036–1043CrossRefPubMed Gancberg D, Di Leo A, Cardoso F et al (2002) Comparison of HER2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol 13:1036–1043CrossRefPubMed
17.
Zurück zum Zitat Edgerton SM, Moore D, Merkel D et al (2003) erbB-2 (HER2) and breast cancer progression. Appl Immunohistochem Mol Morphol 11:214–221PubMed Edgerton SM, Moore D, Merkel D et al (2003) erbB-2 (HER2) and breast cancer progression. Appl Immunohistochem Mol Morphol 11:214–221PubMed
18.
Zurück zum Zitat Zidan J, Dashkovsky I, Stayerman C et al (2005) Comparison of HER2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 93:552–556CrossRefPubMed Zidan J, Dashkovsky I, Stayerman C et al (2005) Comparison of HER2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 93:552–556CrossRefPubMed
19.
Zurück zum Zitat Tanner M, Järvinen P, Isola J (2001) Amplification of HER2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. Cancer Res 61:5345–5348PubMed Tanner M, Järvinen P, Isola J (2001) Amplification of HER2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. Cancer Res 61:5345–5348PubMed
20.
Zurück zum Zitat Meng S, Tripathy D, Shete S et al (2004) HER2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA 101:9393–9398CrossRefPubMed Meng S, Tripathy D, Shete S et al (2004) HER2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA 101:9393–9398CrossRefPubMed
21.
Zurück zum Zitat Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145CrossRefPubMed Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145CrossRefPubMed
22.
Zurück zum Zitat Fleiss JL, Levin B, Paik MC (2003) Statistical methods for rates and proportions, 3rd edn. Wiley, New York, pp 606–607 Fleiss JL, Levin B, Paik MC (2003) Statistical methods for rates and proportions, 3rd edn. Wiley, New York, pp 606–607
23.
Zurück zum Zitat Kleinbaum DG, Kupper LL, Morgenstern H (1982) Epidemiologic research. LL publication, Belmont, CA, p 234 Kleinbaum DG, Kupper LL, Morgenstern H (1982) Epidemiologic research. LL publication, Belmont, CA, p 234
24.
Zurück zum Zitat Vecchi M, Confalonieri S, Nuciforo P et al (2008) Breast cancer metastases are molecularly distinct from their primary tumors. Oncogene 27:2148–2158CrossRefPubMed Vecchi M, Confalonieri S, Nuciforo P et al (2008) Breast cancer metastases are molecularly distinct from their primary tumors. Oncogene 27:2148–2158CrossRefPubMed
25.
Zurück zum Zitat Hayes DF, Smerage J (2008) Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res 14:3646–3650CrossRefPubMed Hayes DF, Smerage J (2008) Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res 14:3646–3650CrossRefPubMed
26.
Zurück zum Zitat Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8:329–340CrossRefPubMed Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8:329–340CrossRefPubMed
27.
Zurück zum Zitat Kagan M, Howard D, Bendele T (2002) Circulating tumor cells as cancer markers, a sample preparation and analysis system. In: Diamandis EP, Fritsche HA, Lilja H et al (eds) Tumor markers: physiology. pathobiology, technology, and clinical applications. AACC Press, Washington (DC), pp 495–498 Kagan M, Howard D, Bendele T (2002) Circulating tumor cells as cancer markers, a sample preparation and analysis system. In: Diamandis EP, Fritsche HA, Lilja H et al (eds) Tumor markers: physiology. pathobiology, technology, and clinical applications. AACC Press, Washington (DC), pp 495–498
28.
Zurück zum Zitat Vona G, Sabile A, Louha M et al (2000) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol 156:57–63PubMed Vona G, Sabile A, Louha M et al (2000) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol 156:57–63PubMed
29.
Zurück zum Zitat Rosenberg R, Gertler R, Friederichs J et al (2002) Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood. Cytometry 49:150–158CrossRefPubMed Rosenberg R, Gertler R, Friederichs J et al (2002) Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood. Cytometry 49:150–158CrossRefPubMed
30.
Zurück zum Zitat Kahn HJ, Presta A, Yang LY et al (2004) Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: correlation with disease stage. Breast Cancer Res Treat 86:237–247CrossRefPubMed Kahn HJ, Presta A, Yang LY et al (2004) Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: correlation with disease stage. Breast Cancer Res Treat 86:237–247CrossRefPubMed
31.
Zurück zum Zitat Balic M, Dandachi N, Hofmann G et al (2005) Comparison of two methods for enumerating circulating tumor cells in carcinoma patients. Cytometry B Clin Cytom 68:25–30PubMed Balic M, Dandachi N, Hofmann G et al (2005) Comparison of two methods for enumerating circulating tumor cells in carcinoma patients. Cytometry B Clin Cytom 68:25–30PubMed
32.
Zurück zum Zitat Benoy IH, Elst H, Philips M et al (2006) Prognostic significance of disseminated tumor cells as detected by quantitative real-time reverse-transcriptase polymerase chain reaction in patients with breast cancer. Clin Breast Cancer 7:146–152CrossRefPubMed Benoy IH, Elst H, Philips M et al (2006) Prognostic significance of disseminated tumor cells as detected by quantitative real-time reverse-transcriptase polymerase chain reaction in patients with breast cancer. Clin Breast Cancer 7:146–152CrossRefPubMed
33.
Zurück zum Zitat Nagrath S, Sequist LV, Maheswaran S et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:1235–1239CrossRefPubMed Nagrath S, Sequist LV, Maheswaran S et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:1235–1239CrossRefPubMed
34.
Zurück zum Zitat Meng S, Tripathy D, Shete S et al (2006) uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci U S A 103:17073–17074CrossRef Meng S, Tripathy D, Shete S et al (2006) uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci U S A 103:17073–17074CrossRef
35.
Zurück zum Zitat Fehm T, Becker S, Duerr-Stoerzer S et al (2007) 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 9:R74CrossRefPubMed Fehm T, Becker S, Duerr-Stoerzer S et al (2007) 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 9:R74CrossRefPubMed
36.
Zurück zum Zitat Tewes M, Aktas B, Welt A, Mueller et al (2008) 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 115(3):581–590CrossRefPubMed Tewes M, Aktas B, Welt A, Mueller et al (2008) 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 115(3):581–590CrossRefPubMed
37.
Zurück zum Zitat Apostolaki S, Perraki M, Kallergi G et al. (2008) Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance. Breast Cancer Res Treat. Nov 19 Apostolaki S, Perraki M, Kallergi G et al. (2008) Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance. Breast Cancer Res Treat. Nov 19
38.
Zurück zum Zitat Ignatiadis M, Kallergi G, Ntoulia M et al (2008) Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer. Clin Cancer Res 14:2593–2600CrossRefPubMed Ignatiadis M, Kallergi G, Ntoulia M et al (2008) Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer. Clin Cancer Res 14:2593–2600CrossRefPubMed
39.
Zurück zum Zitat Wülfing P, Borchard J, Buerger H et al (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12:1715–1720CrossRefPubMed Wülfing P, Borchard J, Buerger H et al (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12:1715–1720CrossRefPubMed
Metadaten
Titel
Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients
verfasst von
Marta Pestrin
Silvia Bessi
Francesca Galardi
Mara Truglia
Annibale Biggeri
Chiara Biagioni
Silvia Cappadona
Laura Biganzoli
Augusto Giannini
Angelo Di Leo
Publikationsdatum
01.12.2009
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2009
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0461-7

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