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

Breast Cancer Research and Treatment

Volumn 138, Issue 2, 2013, Pages 509-517

  Hartkopf, A D ^a   Banys, M ^b   Meier Stiegen, F ^a   Hahn, M ^a   Rohm C ^a   Hoffmann, J ^a   Helms, G ^a   Taran, F A ^a   Wallwiener, M ^c   Walter, C ^a   Neubauer, H ^a   Wallwiener, D ^a   Fehm, T ^d  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b Marienkrankenhaus Hamburg ^*  (Germany)

^c UNIVERSITY OF HEIDELBERG   (Germany)

^d HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

Disseminated tumor cells; DTC; HER2; Primary breast cancer; Survival; Trastuzumab

Indexed keywords

CYTOKERATIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2;

ADULT; ARTICLE; BONE MARROW BIOPSY; BONE MARROW METASTASIS; BREAST CANCER; CANCER MORTALITY; CANCER SURVIVAL; CONTROLLED STUDY; DISEASE FREE SURVIVAL; EARLY CANCER; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; MAJOR CLINICAL STUDY; OVERALL SURVIVAL; PREDICTION; PRIMARY TUMOR; PRIORITY JOURNAL; RECURRENCE RISK; RISK FACTOR; SURVIVAL RATE; SURVIVAL TIME;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; BONE MARROW; BONE MARROW CELLS; BREAST NEOPLASMS; CARCINOMA, DUCTAL, BREAST; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MULTIVARIATE ANALYSIS; NEOPLASM RECURRENCE, LOCAL; PROPORTIONAL HAZARDS MODELS; RECEPTOR, ERBB-2;

EID: 84879418517     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-013-2470-9     Document Type: Article

References (58)

1. 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):S1
2. 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):109-118
3. Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8(5):329-340 (Pubitemid 351596394)
4. 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):793-802 (Pubitemid 41215488)
5. 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):1652-1658 (Pubitemid 26384811)
6. 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):3669-3674 (Pubitemid 32786279)
7. 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):197-202 (Pubitemid 29329158)
8. 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):525-533 (Pubitemid 30117892)
9. 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):3469-3478 (Pubitemid 46594079)
10. 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):23-30 (Pubitemid 27056725)
11. 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):566-571 (Pubitemid 24076481)
12. 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):1392-1400 (Pubitemid 38365234)
13. 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):2967-2976
14. 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):80-86 (Pubitemid 30036339)
15. 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):8152-8162 (Pubitemid 40053373)
16. Hartkopf AD, Banys M, Fehm T (2012) HER2-positive DTCs/CTCs in breast cancer. Recent Results Cancer Res 195:203-215
17. 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-S29
18. 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):783-792 (Pubitemid 32222155)
19. 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):1673-1684 (Pubitemid 41464706)
20. 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):1659-1672 (Pubitemid 41464705)
21. Medina PJ, Goodin S (2008) Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther 30(8):1426-1447
22. 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):97-110
23. 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):118-145 (Pubitemid 350003059)
24. 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):1890-1895 (Pubitemid 32692004)
25. 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):2171-2175 (Pubitemid 40904619)
26. 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):179-184 (Pubitemid 44050767)
27. 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):4019-4024
28. 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. 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):5345-5348 (Pubitemid 32694907)
30. 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):1036-1043
31. Edgerton SM, Moore D II, Merkel D, Thor AD (2003) erbB-2 (HER-2) and breast cancer progression. Appl Immunohistochem Mol Morphol 11(3):214-221 (Pubitemid 37082057)
32. 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):1319-1329
33. 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):R76
34. 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):903-909 (Pubitemid 37429831)
35. 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):1715-1720
36. 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):R59
37. 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):525-534
38. 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):1744-1750
39. 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):1797-1806 (Pubitemid 28550667)
40. 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):9393-9398 (Pubitemid 38812885)
41. 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):R74
42. 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):884-891 (Pubitemid 40270064)
43. 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):8152-8162 (Pubitemid 40053373)
44. 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):2634-2645
45. 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):485-492
46. 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):271-280 (Pubitemid 350159915)
47. 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):8185-8194 (Pubitemid 40053377)
48. 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. 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):851-858 (Pubitemid 47054081)
50. 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):883-889
51. 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):403-412
52. 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):R118
53. 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):283-289
54. 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. 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):653-663
56. 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):2007-2011
57. 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):1807-1813
58. 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):357-363 (Pubitemid 28363797)