Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2013

01-04-2013 | Clinical Trial

The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse

Authors: A. D. Hartkopf, M. Banys, F. Meier-Stiegen, M. Hahn, C. Röhm, J. Hoffmann, G. Helms, F. A. Taran, M. Wallwiener, C. Walter, H. Neubauer, D. Wallwiener, T. Fehm

Published in: Breast Cancer Research and Treatment | Issue 2/2013

Login to get access

Abstract

Overexpression of the HER2-receptor in early breast cancer (EBC) patients is associated with aggressive tumor behavior. However, women suffering from HER2-positive EBC benefit from trastuzumab treatment. As the HER2 status of the primary tumor may differ from that of disseminated tumor cells (DTC) in bone marrow (BM), the aim of this study was (1) to compare the HER2 status of the primary tumor (prim-HER2-status) with that of DTC (DTC-HER2-status) and (2) to analyze the influence of the DTC-HER2-status on patient survival. For this purpose, BM aspirates from 569 EBC patients were analyzed for the presence of DTC. The DTC-HER2-status was identified by a double-staining procedure against cytokeratin and the HER2-receptor. DTC were detected in 151 (27 %) patients. The concordance between the HER2 status of DTC and the primary tumor was 51 %. In patients with detectable DTC, mean disease-free survival was 77.44 (95 % CI 74.72–80.17) months for DTC-HER2-negative and 55.15 (95 % CI 48.57–61.79) months for DTC-HER2-positive patients (p = 0.044). The multivariate analysis showed that the DTC-HER2-status was an independent predictor of disease-free survival. In conclusion, the presence of HER2-positive DTC in EBC patients is associated with an increased risk of relapse. Due to the low concordance between the HER2 status of the primary tumor and DTC, only a minority (13 %) of the DTC-HER2-positive patients was treated with trastuzumab. These patients might, however, benefit from HER2-directed therapy.
Literature
1.
go back to reference Fehm T, Muller V, Alix-Panabieres C, Pantel K (2008) Micrometastatic spread in breast cancer: detection, molecular characterization and clinical relevance. Breast Cancer Res 10(Suppl 1):S1PubMedCrossRef Fehm T, Muller V, Alix-Panabieres C, Pantel K (2008) Micrometastatic spread in breast cancer: detection, molecular characterization and clinical relevance. Breast Cancer Res 10(Suppl 1):S1PubMedCrossRef
2.
go back to reference Banys M, Hartkopf AD, Krawczyk N, Becker S, Fehm T (2012) Clinical implications of the detection of circulating tumor cells in breast cancer patients. Biomark Med 6(1):109–118PubMedCrossRef Banys M, Hartkopf AD, Krawczyk N, Becker S, Fehm T (2012) Clinical implications of the detection of circulating tumor cells in breast cancer patients. Biomark Med 6(1):109–118PubMedCrossRef
3.
go back to reference Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8(5):329–340PubMedCrossRef Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8(5):329–340PubMedCrossRef
4.
go back to reference Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga JY, Marth C, Oruzio D, Wiedswang G, Solomayer EF, Kundt G, Strobl B, Fehm T, Wong GY, Bliss J, Vincent-Salomon A, Pantel K (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353(8):793–802PubMedCrossRef Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga JY, Marth C, Oruzio D, Wiedswang G, Solomayer EF, Kundt G, Strobl B, Fehm T, Wong GY, Bliss J, Vincent-Salomon A, Pantel K (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353(8):793–802PubMedCrossRef
5.
go back to reference Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, Kaul S, Bastert G (1996) Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 88(22):1652–1658PubMedCrossRef Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, Kaul S, Bastert G (1996) Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 88(22):1652–1658PubMedCrossRef
6.
go back to reference Gebauer G, Fehm T, Merkle E, Beck EP, Lang N, Jager W (2001) Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up. J Clin Oncol 19(16):3669–3674PubMed Gebauer G, Fehm T, Merkle E, Beck EP, Lang N, Jager W (2001) Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up. J Clin Oncol 19(16):3669–3674PubMed
7.
go back to reference Mansi JL, Gogas H, Bliss JM, Gazet JC, Berger U, Coombes RC (1999) Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet 354(9174):197–202PubMedCrossRef Mansi JL, Gogas H, Bliss JM, Gazet JC, Berger U, Coombes RC (1999) Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet 354(9174):197–202PubMedCrossRef
8.
go back to reference Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmuller G, Schlimok G (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(8):525–533PubMedCrossRef Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmuller G, Schlimok G (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(8):525–533PubMedCrossRef
9.
go back to reference Wiedswang G, Borgen E, Karesen R, Kvalheim G, Nesland JM, Qvist H, Schlichting E, Sauer T, Janbu J, Harbitz T, Naume B (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21(18):3469–3478PubMedCrossRef Wiedswang G, Borgen E, Karesen R, Kvalheim G, Nesland JM, Qvist H, Schlichting E, Sauer T, Janbu J, Harbitz T, Naume B (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21(18):3469–3478PubMedCrossRef
10.
go back to reference Molino A, Pelosi G, Turazza M, Sperotto L, Bonetti A, Nortilli R, Fattovich G, Alaimo C, Piubello Q, Pavanel F, Micciolo R, Cetto GL (1997) Bone marrow micrometastases in 109 breast cancer patients: correlations with clinical and pathological features and prognosis. Breast Cancer Res Treat 42(1):23–30PubMedCrossRef Molino A, Pelosi G, Turazza M, Sperotto L, Bonetti A, Nortilli R, Fattovich G, Alaimo C, Piubello Q, Pavanel F, Micciolo R, Cetto GL (1997) Bone marrow micrometastases in 109 breast cancer patients: correlations with clinical and pathological features and prognosis. Breast Cancer Res Treat 42(1):23–30PubMedCrossRef
11.
go back to reference Harbeck N, Untch M, Pache L, Eiermann W (1994) Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up. Br J Cancer 69(3):566–571PubMedCrossRef Harbeck N, Untch M, Pache L, Eiermann W (1994) Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up. Br J Cancer 69(3):566–571PubMedCrossRef
12.
go back to reference Pierga JY, Bonneton C, Vincent-Salomon A, de Cremoux P, Nos C, Blin N, Pouillart P, Thiery JP, Magdelenat H (2004) Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res 10(4):1392–1400PubMedCrossRef Pierga JY, Bonneton C, Vincent-Salomon A, de Cremoux P, Nos C, Blin N, Pouillart P, Thiery JP, Magdelenat H (2004) Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res 10(4):1392–1400PubMedCrossRef
13.
go back to reference Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, Borgen E, Rack B, Braun S, Sommer H, Solomayer E, Pantel K, Nesland J, Friese K, Naume B (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse—a European pooled analysis. Clin Cancer Res 17(9):2967–2976PubMedCrossRef Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, Borgen E, Rack B, Braun S, Sommer H, Solomayer E, Pantel K, Nesland J, Friese K, Naume B (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse—a European pooled analysis. Clin Cancer Res 17(9):2967–2976PubMedCrossRef
14.
go back to reference Braun S, Kentenich C, Janni W, Hepp F, de Waal J, Willgeroth F, Sommer H, Pantel K (2000) 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 18(1):80–86PubMed Braun S, Kentenich C, Janni W, Hepp F, de Waal J, Willgeroth F, Sommer H, Pantel K (2000) 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 18(1):80–86PubMed
15.
go back to reference Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10(24):8152–8162PubMedCrossRef Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10(24):8152–8162PubMedCrossRef
16.
go back to reference Hartkopf AD, Banys M, Fehm T (2012) HER2-positive DTCs/CTCs in breast cancer. Recent Results Cancer Res 195:203–215PubMedCrossRef Hartkopf AD, Banys M, Fehm T (2012) HER2-positive DTCs/CTCs in breast cancer. Recent Results Cancer Res 195:203–215PubMedCrossRef
17.
go back to reference Vogel C, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ (2001) First-line, single-agent Herceptin(trastuzumab) in metastatic breast cancer: a preliminary report. Eur J Cancer 37(Suppl 1):S25–S29PubMedCrossRef Vogel C, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ (2001) First-line, single-agent Herceptin(trastuzumab) in metastatic breast cancer: a preliminary report. Eur J Cancer 37(Suppl 1):S25–S29PubMedCrossRef
18.
go back to reference Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792PubMedCrossRef Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792PubMedCrossRef
19.
go back to reference Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684PubMedCrossRef Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684PubMedCrossRef
20.
go back to reference Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672PubMedCrossRef Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672PubMedCrossRef
21.
go back to reference Medina PJ, Goodin S (2008) Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther 30(8):1426–1447PubMedCrossRef Medina PJ, Goodin S (2008) Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther 30(8):1426–1447PubMedCrossRef
22.
go back to reference Huang Z, Brdlik C, Jin P, Shepard HM (2009) A pan-HER approach for cancer therapy: background, current status and future development. Expert Opin Biol Ther 9(1):97–110PubMedCrossRef Huang Z, Brdlik C, Jin P, Shepard HM (2009) A pan-HER approach for cancer therapy: background, current status and future development. Expert Opin Biol Ther 9(1):97–110PubMedCrossRef
23.
go back to reference Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (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(1):118–145PubMedCrossRef Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (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(1):118–145PubMedCrossRef
24.
go back to reference Braun S, Schlimok G, Heumos I, Schaller G, Riethdorf L, Riethmuller G, Pantel K (2001) ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients. Cancer Res 61(5):1890–1895PubMed Braun S, Schlimok G, Heumos I, Schaller G, Riethdorf L, Riethmuller G, Pantel K (2001) ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients. Cancer Res 61(5):1890–1895PubMed
25.
go back to reference Becker S, Becker-Pergola G, Fehm T, Wallwiener D, Solomayer EF (2005) Her2 expression on disseminated tumor cells from bone marrow of breast cancer patients. Anticancer Res 25(3B):2171–2175PubMed Becker S, Becker-Pergola G, Fehm T, Wallwiener D, Solomayer EF (2005) Her2 expression on disseminated tumor cells from bone marrow of breast cancer patients. Anticancer Res 25(3B):2171–2175PubMed
26.
go back to reference Solomayer EF, Becker S, Pergola-Becker G, Bachmann R, Kramer B, Vogel U, Neubauer H, Wallwiener D, Huober J, Fehm TN (2006) Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients. Breast Cancer Res Treat 98(2):179–184PubMedCrossRef Solomayer EF, Becker S, Pergola-Becker G, Bachmann R, Kramer B, Vogel U, Neubauer H, Wallwiener D, Huober J, Fehm TN (2006) Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients. Breast Cancer Res Treat 98(2):179–184PubMedCrossRef
27.
go back to reference Krawczyk N, Banys M, Neubauer H, Solomayer EF, Gall C, Hahn M, Becker S, Bachmann R, Wallwiener D, Fehm T (2009) HER2 status on persistent disseminated tumor cells after adjuvant therapy may differ from initial HER2 status on primary tumor. Anticancer Res 29(10):4019–4024PubMed Krawczyk N, Banys M, Neubauer H, Solomayer EF, Gall C, Hahn M, Becker S, Bachmann R, Wallwiener D, Fehm T (2009) HER2 status on persistent disseminated tumor cells after adjuvant therapy may differ from initial HER2 status on primary tumor. Anticancer Res 29(10):4019–4024PubMed
28.
go back to reference Jückstock J, Rack B, Schindlbeck C, Hofmann S, Zill B, Rengel A, Feuerecker R, Mylonas I, Blankenstein T, Kost B, Janni W, Friese K (2008) Treatment with trastuzumab in recurrence free patients with early breast cancer and persistent disseminated tumor cells (DTC) in bone marrow. San Antonio Breast Cancer Symposium Jückstock J, Rack B, Schindlbeck C, Hofmann S, Zill B, Rengel A, Feuerecker R, Mylonas I, Blankenstein T, Kost B, Janni W, Friese K (2008) Treatment with trastuzumab in recurrence free patients with early breast cancer and persistent disseminated tumor cells (DTC) in bone marrow. San Antonio Breast Cancer Symposium
29.
go back to reference Tanner M, Jarvinen P, Isola J (2001) Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. Cancer Res 61(14):5345–5348PubMed Tanner M, Jarvinen P, Isola J (2001) Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. Cancer Res 61(14):5345–5348PubMed
30.
go back to reference Gancberg D, Di Leo A, Cardoso F, Rouas G, Pedrocchi M, Paesmans M, Verhest A, Bernard-Marty C, Piccart MJ, Larsimont D (2002) Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol 13(7):1036–1043PubMedCrossRef Gancberg D, Di Leo A, Cardoso F, Rouas G, Pedrocchi M, Paesmans M, Verhest A, Bernard-Marty C, Piccart MJ, Larsimont D (2002) Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol 13(7):1036–1043PubMedCrossRef
31.
go back to reference Edgerton SM, Moore D II, Merkel D, Thor AD (2003) erbB-2 (HER-2) and breast cancer progression. Appl Immunohistochem Mol Morphol 11(3):214–221PubMedCrossRef Edgerton SM, Moore D II, Merkel D, Thor AD (2003) erbB-2 (HER-2) and breast cancer progression. Appl Immunohistochem Mol Morphol 11(3):214–221PubMedCrossRef
32.
go back to reference Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ (2009) Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer. Ann Oncol 20(8):1319–1329PubMedCrossRef Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ (2009) Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer. Ann Oncol 20(8):1319–1329PubMedCrossRef
33.
go back to reference Fehm T, Krawczyk N, Solomayer EF, Becker-Pergola G, Durr-Storzer S, Neubauer H, Seeger H, Staebler A, Wallwiener D, Becker S (2008) ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients. Breast Cancer Res 10(5):R76PubMedCrossRef Fehm T, Krawczyk N, Solomayer EF, Becker-Pergola G, Durr-Storzer S, Neubauer H, Seeger H, Staebler A, Wallwiener D, Becker S (2008) ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients. Breast Cancer Res 10(5):R76PubMedCrossRef
34.
go back to reference Hemsen A, Riethdorf L, Brunner N, Berger J, Ebel S, Thomssen C, Janicke F, Pantel K (2003) Comparative evaluation of urokinase-type plasminogen activator receptor expression in primary breast carcinomas and on metastatic tumor cells. Int J Cancer 107(6):903–909PubMedCrossRef Hemsen A, Riethdorf L, Brunner N, Berger J, Ebel S, Thomssen C, Janicke F, Pantel K (2003) Comparative evaluation of urokinase-type plasminogen activator receptor expression in primary breast carcinomas and on metastatic tumor cells. Int J Cancer 107(6):903–909PubMedCrossRef
35.
go back to reference Wulfing P, Borchard J, Buerger H, Heidl S, Zanker KS, Kiesel L, Brandt B (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12(6):1715–1720PubMedCrossRef Wulfing P, Borchard J, Buerger H, Heidl S, Zanker KS, Kiesel L, Brandt B (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12(6):1715–1720PubMedCrossRef
36.
go back to reference Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D, Kimmig R, Kasimir-Bauer S (2009) 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 Res 11(4):R59PubMedCrossRef Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D, Kimmig R, Kasimir-Bauer S (2009) 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 Res 11(4):R59PubMedCrossRef
37.
go back to reference Apostolaki S, Perraki M, Kallergi G, Kafousi M, Papadopoulos S, Kotsakis A, Pallis A, Xenidis N, Kalmanti L, Kalbakis K, Agelaki S, Kalykaki A, Stournaras C, Stathopoulos E, Georgoulias V, Mavroudis D (2009) 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 117(3):525–534PubMedCrossRef Apostolaki S, Perraki M, Kallergi G, Kafousi M, Papadopoulos S, Kotsakis A, Pallis A, Xenidis N, Kalmanti L, Kalbakis K, Agelaki S, Kalykaki A, Stournaras C, Stathopoulos E, Georgoulias V, Mavroudis D (2009) 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 117(3):525–534PubMedCrossRef
38.
go back to reference Georgoulias V, Bozionelou V, Agelaki S, Perraki M, Apostolaki S, Kallergi G, Kalbakis K, Xyrafas A, Mavroudis D (2012) Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study. Ann Oncol 23(7):1744–1750PubMedCrossRef Georgoulias V, Bozionelou V, Agelaki S, Perraki M, Apostolaki S, Kallergi G, Kalbakis K, Xyrafas A, Mavroudis D (2012) Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study. Ann Oncol 23(7):1744–1750PubMedCrossRef
39.
go back to reference Roetger A, Merschjann A, Dittmar T, Jackisch C, Barnekow A, Brandt B (1998) Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model. Am J Pathol 153(6):1797–1806PubMedCrossRef Roetger A, Merschjann A, Dittmar T, Jackisch C, Barnekow A, Brandt B (1998) Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model. Am J Pathol 153(6):1797–1806PubMedCrossRef
40.
go back to reference Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, Beitsch P, Khan A, Euhus D, Osborne C, Frenkel E, Hoover S, Leitch M, Clifford E, Vitetta E, Morrison L, Herlyn D, Terstappen LW, Fleming T, Fehm T, Tucker T, Lane N, Wang J, Uhr J (2004) HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA 101(25):9393–9398PubMedCrossRef Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, Beitsch P, Khan A, Euhus D, Osborne C, Frenkel E, Hoover S, Leitch M, Clifford E, Vitetta E, Morrison L, Herlyn D, Terstappen LW, Fleming T, Fehm T, Tucker T, Lane N, Wang J, Uhr J (2004) HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA 101(25):9393–9398PubMedCrossRef
41.
go back to reference Fehm T, Becker S, Duerr-Stoerzer S, Sotlar K, Mueller V, Wallwiener D, Lane N, Solomayer E, Uhr J (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(5):R74PubMedCrossRef Fehm T, Becker S, Duerr-Stoerzer S, Sotlar K, Mueller V, Wallwiener D, Lane N, Solomayer E, Uhr J (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(5):R74PubMedCrossRef
42.
go back to reference Janni W, Rack B, Schindlbeck C, Strobl B, Rjosk D, Braun S, Sommer H, Pantel K, Gerber B, Friese K (2005) The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence. Cancer 103(5):884–891PubMedCrossRef Janni W, Rack B, Schindlbeck C, Strobl B, Rjosk D, Braun S, Sommer H, Pantel K, Gerber B, Friese K (2005) The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence. Cancer 103(5):884–891PubMedCrossRef
43.
go back to reference Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10(24):8152–8162PubMedCrossRef Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10(24):8152–8162PubMedCrossRef
44.
go back to reference Riethdorf S, Muller V, Zhang L, Rau T, Loibl S, Komor M, Roller M, Huober J, Fehm T, Schrader I, Hilfrich J, Holms F, Tesch H, Eidtmann H, Untch M, von Minckwitz G, Pantel K (2010) Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res 16(9):2634–2645PubMedCrossRef Riethdorf S, Muller V, Zhang L, Rau T, Loibl S, Komor M, Roller M, Huober J, Fehm T, Schrader I, Hilfrich J, Holms F, Tesch H, Eidtmann H, Untch M, von Minckwitz G, Pantel K (2010) Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res 16(9):2634–2645PubMedCrossRef
45.
go back to reference Rack B, Juckstock J, Gunthner-Biller M, Andergassen U, Neugebauer J, Hepp P, Schoberth A, Mayr D, Zwingers T, Schindlbeck C, Friese K, Janni W (2012) Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients. Arch Gynecol Obstet 285(2):485–492PubMedCrossRef Rack B, Juckstock J, Gunthner-Biller M, Andergassen U, Neugebauer J, Hepp P, Schoberth A, Mayr D, Zwingers T, Schindlbeck C, Friese K, Janni W (2012) Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients. Arch Gynecol Obstet 285(2):485–492PubMedCrossRef
46.
go back to reference Bernhard H, Neudorfer J, Gebhard K, Conrad H, Hermann C, Nahrig J, Fend F, Weber W, Busch DH, Peschel C (2008) Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer. Cancer Immunol Immunother 57(2):271–280PubMedCrossRef Bernhard H, Neudorfer J, Gebhard K, Conrad H, Hermann C, Nahrig J, Fend F, Weber W, Busch DH, Peschel C (2008) Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer. Cancer Immunol Immunother 57(2):271–280PubMedCrossRef
47.
go back to reference Bozionellou V, Mavroudis D, Perraki M, Papadopoulos S, Apostolaki S, Stathopoulos E, Stathopoulou A, Lianidou E, Georgoulias V (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(24):8185–8194PubMedCrossRef Bozionellou V, Mavroudis D, Perraki M, Papadopoulos S, Apostolaki S, Stathopoulos E, Stathopoulou A, Lianidou E, Georgoulias V (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(24):8185–8194PubMedCrossRef
48.
go back to reference Lueftner D, Dilk H, Henschke P, Geppert R, Dietel M, Stein H, Wernecke K, Possinger K, Heine B (2004) Concordance of HER-2/neu expression of primary breast carcinomas and their metachronous distant metastases: results of a 10 year retrospective search in two university institutes of pathology (abstr. 3045). Breast Cancer Res Treat Suppl 88:127 Lueftner D, Dilk H, Henschke P, Geppert R, Dietel M, Stein H, Wernecke K, Possinger K, Heine B (2004) Concordance of HER-2/neu expression of primary breast carcinomas and their metachronous distant metastases: results of a 10 year retrospective search in two university institutes of pathology (abstr. 3045). Breast Cancer Res Treat Suppl 88:127
49.
go back to reference Apostolaki S, Perraki M, Pallis A, Bozionelou V, Agelaki S, Kanellou P, Kotsakis A, Politaki E, Kalbakis K, Kalykaki A, Vamvakas L, Georgoulias V, Mavroudis D (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(5):851–858PubMedCrossRef Apostolaki S, Perraki M, Pallis A, Bozionelou V, Agelaki S, Kanellou P, Kotsakis A, Politaki E, Kalbakis K, Kalykaki A, Vamvakas L, Georgoulias V, Mavroudis D (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(5):851–858PubMedCrossRef
50.
go back to reference Ignatiadis M, Perraki M, Apostolaki S, Politaki E, Xenidis N, Kafousi M, Stathopoulos E, Lianidou E, Sotiriou C, Georgoulias V, Mavroudis D (2007) Molecular detection and prognostic value of circulating cytokeratin-19 messenger RNA-positive and HER2 messenger RNA-positive cells in the peripheral blood of women with early-stage breast cancer. Clin Breast Cancer 7(11):883–889PubMedCrossRef Ignatiadis M, Perraki M, Apostolaki S, Politaki E, Xenidis N, Kafousi M, Stathopoulos E, Lianidou E, Sotiriou C, Georgoulias V, Mavroudis D (2007) Molecular detection and prognostic value of circulating cytokeratin-19 messenger RNA-positive and HER2 messenger RNA-positive cells in the peripheral blood of women with early-stage breast cancer. Clin Breast Cancer 7(11):883–889PubMedCrossRef
51.
go back to reference Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, Lattrich C, Lohberg CR, Solomayer E, Rack B, Riethdorf S, Klein C, Schindlbeck C, Brocker K, Kasimir-Bauer S, Wallwiener D, Pantel K (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 124(2):403–412PubMedCrossRef Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, Lattrich C, Lohberg CR, Solomayer E, Rack B, Riethdorf S, Klein C, Schindlbeck C, Brocker K, Kasimir-Bauer S, Wallwiener D, Pantel K (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 124(2):403–412PubMedCrossRef
52.
go back to reference Muller V, Riethdorf S, Rack B, Janni W, Fasching P, Solomayer E, Aktas B, Kasimir-Bauer S, Pantel K, Fehm T, Study Group TD (2012) Prognostic impact of circulating tumor cells assessed with the CellSearch AssayTM and AdnaTest BreastTM in metastatic breast cancer patients: the DETECT study. Breast Cancer Res 14(4):R118PubMedCrossRef Muller V, Riethdorf S, Rack B, Janni W, Fasching P, Solomayer E, Aktas B, Kasimir-Bauer S, Pantel K, Fehm T, Study Group TD (2012) Prognostic impact of circulating tumor cells assessed with the CellSearch AssayTM and AdnaTest BreastTM in metastatic breast cancer patients: the DETECT study. Breast Cancer Res 14(4):R118PubMedCrossRef
53.
go back to reference Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C, Gori S, Coombes CR, Stebbing J, Biganzoli L, Buyse M, Di Leo A (2012) Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study. Breast Cancer Res Treat 134(1):283–289PubMedCrossRef Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C, Gori S, Coombes CR, Stebbing J, Biganzoli L, Buyse M, Di Leo A (2012) Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study. Breast Cancer Res Treat 134(1):283–289PubMedCrossRef
54.
go back to reference Hartkopf AD, Banys M, Krawczyk N, Staebler A, Becker S, Hoffmann J, Hahn M, Wallwiener M, Fehm T (2012) Bone marrow versus sentinel lymph node involvement in breast cancer: a comparison of early hematogenous and early lymphatic tumor spread. Breast Cancer Res Treat 131(2):501–508 Hartkopf AD, Banys M, Krawczyk N, Staebler A, Becker S, Hoffmann J, Hahn M, Wallwiener M, Fehm T (2012) Bone marrow versus sentinel lymph node involvement in breast cancer: a comparison of early hematogenous and early lymphatic tumor spread. Breast Cancer Res Treat 131(2):501–508
55.
go back to reference de Boer M, van Deurzen CH, van Dijck JA, Borm GF, van Diest PJ, Adang EM, Nortier JW, Rutgers EJ, Seynaeve C, Menke-Pluymers MB, Bult P, Tjan-Heijnen VC (2009) Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med 361(7):653–663PubMedCrossRef de Boer M, van Deurzen CH, van Dijck JA, Borm GF, van Diest PJ, Adang EM, Nortier JW, Rutgers EJ, Seynaeve C, Menke-Pluymers MB, Bult P, Tjan-Heijnen VC (2009) Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med 361(7):653–663PubMedCrossRef
56.
go back to reference Diel IJ, Jaschke A, Solomayer EF, Gollan C, Bastert G, Sohn C, Schuetz F (2008) Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol 19(12):2007–2011PubMedCrossRef Diel IJ, Jaschke A, Solomayer EF, Gollan C, Bastert G, Sohn C, Schuetz F (2008) Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol 19(12):2007–2011PubMedCrossRef
57.
go back to reference Rack B, Juckstock J, Genss EM, Schoberth A, Schindlbeck C, Strobl B, Heinrigs M, Rammel G, Zwingers T, Sommer H, Friese K, Janni W (2010) Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer. Anticancer Res 30(5):1807–1813PubMed Rack B, Juckstock J, Genss EM, Schoberth A, Schindlbeck C, Strobl B, Heinrigs M, Rammel G, Zwingers T, Sommer H, Friese K, Janni W (2010) Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer. Anticancer Res 30(5):1807–1813PubMed
58.
go back to reference Diel IJ, Solomayer EF, Costa SD, Gollan C, Goerner R, Wallwiener D, Kaufmann M, Bastert G (1998) Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 339(6):357–363PubMedCrossRef Diel IJ, Solomayer EF, Costa SD, Gollan C, Goerner R, Wallwiener D, Kaufmann M, Bastert G (1998) Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 339(6):357–363PubMedCrossRef
Metadata
Title
The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse
Authors
A. D. Hartkopf
M. Banys
F. Meier-Stiegen
M. Hahn
C. Röhm
J. Hoffmann
G. Helms
F. A. Taran
M. Wallwiener
C. Walter
H. Neubauer
D. Wallwiener
T. Fehm
Publication date
01-04-2013
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2013
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-013-2470-9

Other articles of this Issue 2/2013

Breast Cancer Research and Treatment 2/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine