Top

Published in:

01-12-2004 | Commentary

Bone marrow micrometastases and circulating tumor cells: current aspects and future perspectives

Authors: Volkmar Müller, Klaus Pantel

Published in: Breast Cancer Research | Issue 6/2004

Abstract

Early tumor cell dissemination at the single-cell level can be revealed in patients with breast cancer by using sensitive immunocytochemical and molecular assays. Recent clinical studies involving more than 4000 breast cancer patients demonstrated that the presence of disseminated tumor cells in bone marrow at primary diagnosis is an independent prognostic factor. In addition, various assays for the detection of circulating tumor cells in the peripheral blood have recently been developed and some studies also suggest a potential clinical relevance of this measure. These findings provide the basis for the potential use of disseminated tumor cells in bone marrow or blood as markers for the early assessment of therapeutic response in prospective clinical trials.

Pantel K, Brakenhoff RH: Dissecting the metastatic cascade. Nat Rev Cancer. 2004, 4: 448-456. 10.1038/nrc1370.CrossRefPubMed

Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, et al: Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000, 342: 525-533. 10.1056/NEJM200002243420801.CrossRefPubMed

Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, Kaul S, Bastert G: Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst. 1996, 88: 1652-1658. 10.1093/jnci/88.22.1652.CrossRefPubMed

Gebauer G, Fehm T, Merkle E, Beck EP, Lang N, Jager W: Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up. J Clin Oncol. 2001, 19: 3669-3674.PubMed

Mansi JL, Gogas H, Bliss JM, Gazet JC, Berger U, Coombes RC: Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet. 1999, 354: 197-202. 10.1016/S0140-6736(98)10175-7.CrossRefPubMed

Wiedswang G, Borgen E, Karesen R, Kvalheim G, Nesland JM, Qvist H, Schlichting E, Sauer T, Janbu J, Harbitz T, et al: Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol. 2003, 21: 3469-3478. 10.1200/JCO.2003.02.009.CrossRefPubMed

Pierga JY, Bonneton C, Vincent-Salomon A, de Cremoux P, Nos C, Blin N, Pouillart P, Thiery JP, Magdelenat H: 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, 10: 1392-1400.CrossRefPubMed

Braun S, Vogl FD, Schlimok G, Diel I, Janni W, Gerber B, Gebauer G, Coombes RC, Pierga JY, Naume B, et al: Pooled analysis of prognostic impact of bone marrow micrometastasis: 10-year survival of 4199 breast cancer patients. Breast Cancer Res Treat. 2003, 82 (Suppl 1): S8-

Naume B, Wiedswang G, Borgen E, Kvalheim G, Karesen R, Qvist H, Janbu J, Harbitz T, Nesland JM: The prognostic value of isolated tumor cells in bone marrow in breast cancer patients: evaluation of morphological categories and the number of clinically significant cells. Clin Cancer Res. 2004, 10: 3091-3097.CrossRefPubMed

10.

Janni W, Hepp F, Rjosk D, Kentenich C, Strobl B, Schindlbeck C, Hantschmann P, Sommer H, Pantel K, Braun S: The fate and prognostic value of occult metastatic cells in the bone marrow of patients with breast carcinoma between primary treatment and recurrence. Cancer. 2001, 92: 46-53. 10.1002/1097-0142(20010701)92:1<46::AID-CNCR1290>3.0.CO;2-6.CrossRefPubMed

11.

Wiedswang G, Borgen E, Karensen R, Qvist H, Naume B: The presence of isolated tumor cells in bone marrow three years after diagnosis in disease free breast cancer patients predicts an unfavorable outcome. Breast Cancer Res Treat. 2003, 82 (Suppl 1): S8-

12.

Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, et al: A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003, 349: 1793-1802. 10.1056/NEJMoa032312.CrossRefPubMed

13.

Mehes G, Witt A, Kubista E, Ambros PF: Circulating breast cancer cells are frequently apoptotic. Am J Pathol. 2001, 159: 17-20.CrossRefPubMedPubMedCentral

14.

Terstappen LW, Rao C, Gross S, Weiss AJ: Peripheral blood tumor cell load reflects the clinical activity of the disease in patients with carcinoma of the breast. Int J Oncol. 2000, 17: 573-578.PubMed

15.

Smith BM, Slade MJ, English J, Graham H, Luchtenborg M, Sinnett HD, Cross NC, Coombes RC: Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemical techniques. J Clin Oncol. 2000, 18: 1432-1439.PubMed

16.

Stathopoulou A, Vlachonikolis I, Mavroudis D, Perraki M, Kouroussis C, Apostolaki S, Malamos N, Kakolyris S, Kotsakis A, Xenidis N, et al: 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, 20: 3404-3412. 10.1200/JCO.2002.08.135.CrossRefPubMed

17.

Weigelt B, Bosma AJ, Hart AA, Rodenhuis S, van 't Veer LJ: Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients. Br J Cancer. 2003, 88: 1091-1094. 10.1038/sj.bjc.6600868.CrossRefPubMedPubMedCentral

18.

Mueller V, Stahmann N, Zabel T, Goetz A, Jaenicke F, Thomssen C, Pantel K: Detection of circulating tumor cells in patients with primary and metastatic breast cancer by enhanced gradient centrifugation. Breast Cancer Res Treat. 2003, 82 (Suppl 1): S94-

19.

Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, et al: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004, 351: 781-791. 10.1056/NEJMoa040766.CrossRefPubMed

20.

Mueller P, Carroll P, Bowers E, Moore D, Cher M, Presti J, Wessman M, Pallavicini MG: Low frequency epithelial cells in bone marrow aspirates from prostate carcinoma patients are cytogenetically aberrant. Cancer. 1998, 83: 538-546. 10.1002/(SICI)1097-0142(19980801)83:3<538::AID-CNCR23>3.3.CO;2-R.CrossRefPubMed

21.

Fehm T, Sagalowsky A, Clifford E, Beitsch P, Saboorian H, Euhus D, Meng S, Morrison L, Tucker T, Lane N, et al: Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res. 2002, 8: 2073-2084.PubMed

22.

Solakoglu O, Maierhofer C, Lahr G, Breit E, Scheunemann P, Heumos I, Pichlmeier U, Schlimok G, Oberneder R, Kollermann MW, et al: Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors. Proc Natl Acad Sci USA. 2002, 99: 2246-2251. 10.1073/pnas.042372199.CrossRefPubMedPubMedCentral

23.

Klein CA, Blankenstein TJ, Schmidt-Kittler O, Petronio M, Polzer B, Stoecklein NH, Riethmuller G: Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet. 2002, 360: 683-689. 10.1016/S0140-6736(02)09838-0.CrossRefPubMed

24.

Schmidt-Kittler O, Ragg T, Daskalakis A, Granzow M, Ahr A, Blankenstein TJ, Kaufmann M, Diebold J, Arnholdt H, Muller P, et al: From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci USA. 2003, 100: 7737-7742. 10.1073/pnas.1331931100.CrossRefPubMedPubMedCentral

25.

Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, Borgen PI, Clark G, Edge SB, Hayes DF, et al: Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol. 2002, 20: 3628-3636. 10.1200/JCO.2002.02.026.CrossRefPubMed

Title: Bone marrow micrometastases and circulating tumor cells: current aspects and future perspectives
Authors: Volkmar Müller
Klaus Pantel
Publication date: 01-12-2004
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 6/2004
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr942

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2004

Endocrinology and hormone therapy in breast cancer: Aromatase inhibitors versus antioestrogens

Articles selected in September 2004

The Na+–H+exchanger-1 induces cytoskeletal changes involving reciprocal RhoA and Rac1 signaling, resulting in motility and invasion in MDA-MB-435 cells

Birthweight, parental age, birth order and breast cancer risk in African-American and white women: a population-based case–control study

Frequency of CHEK2 mutations in a population based, case–control study of breast cancer in young women

Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

Keynote webinar | Spotlight on antibody–drug conjugates in cancer