Prognostic value of circulating tumor cells in primary and metastatic breast cancer

Expert Review of Anticancer Therapy

Volumn 12, Issue 2, 2012, Pages 203-214

  Aurilio, Gaetano ^a   Sciandivasci, Angela ^a   Munzone, Elisabetta ^a   Sandri, Maria Teresa ^a   Zorzino, Laura ^a   Cassatella, Maria Cristina ^a   Verri, Elena ^a   Rocca, Maria Cossu ^a   Nolè, Franco ^a  

^a EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

Author keywords

breast cancer; cell characterization; circulating tumor cells; detection method; prediction; prognosis

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FOCAL ADHESION KINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LAPATINIB; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN KINASE B; SOMATOMEDIN C RECEPTOR; TRASTUZUMAB; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 2;

BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER DIAGNOSIS; CANCER PROGNOSIS; CANCER SURVIVAL; CELL CULTURE EQUIPMENT; CELL ISOLATION; CIRCULATING TUMOR CELL; CYTOLOGY; CYTOMETRY; DENSITY GRADIENT CENTRIFUGATION; DISEASE FREE SURVIVAL; DISTANT METASTASIS FREE SURVIVAL; ENRICHMENT CULTURE; FILTRATION; GENE EXPRESSION; HUMAN; IMMUNOMAGNETIC SEPARATION; METASTASIS; NUCLEIC ACID ANALYSIS; OVERALL SURVIVAL; PRIMARY TUMOR; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SURVIVAL PREDICTION;

ANIMALS; BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; FEMALE; HUMANS; NEOPLASTIC CELLS, CIRCULATING; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 84856889339     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.11.208     Document Type: Review

References (76)

1. Jemal A, Siegel R, Ward E et al. Cancer statistics, 2009. CA Cancer J. Clin. 59(4), 225-249 (2009).
2. Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nat. Rev. Cancer 4(6), 448-456 (2004). (Pubitemid 38745530)
3. Braun S, Vogl FD, Naume B et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N. Engl. J. Med. 353(8), 793-802 (2005). (Pubitemid 41215488)
4. Janni W, Vogl FD, Wiedswang G et al. 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 (2011).
5. Braun S, Kentenich C, Janni W et al. 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 (2000). (Pubitemid 30036339)
6. Zhao S, Liu Y, Zhang Q et al. The prognostic role of circulating tumor cells (CTCs) detected by RT-PCR in breast cancer: A meta-analysis of published literature. Breast Cancer Res. Treat. 130(3), 809-816 (2011).
7. Xenidis N, Ignatiadis M, Apostolaki S et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J. Clin. Oncol. 27(13), 2177-2184 (2009). .. Study suggesting that chemotherapy-resistant circulating tumor cells (CTCs) during or after adjuvant treatment may predict the ineffectiveness of current or previous therapy.
8. Ignatiadis M, Xenidis N, Perraki M et al. Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer. J. Clin. Oncol. 25(33), 5194-5202 (2007). .. Study highlighting the association between CTCs and breast cancer subtypes and hypothesized the possibility to define prognostic groups with different clinical outcome. (Pubitemid 350232250)
9. Rack BK, Schindlbeck C, Andergassen U et al. Use of circulating tumor cells (CTC) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy to predict risk for relapse: The SUCCESS trial. J. Clin. Oncol. 28, 15s (2010).
10. Fehm T, Hoffmann O, Aktas B et al. 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 (2009).
11. Pierga JY, Bonneton C, Vincent-Salomon A et al. 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 (2004). (Pubitemid 38365234)
12. Cristofanilli M, Budd GT, Ellis MJ et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351(8), 781-791 (2004). .. Prospective study that evaluated the prognostic and predictive role of CTCs and led to the US FDA clearance of the CellSearch® System for CTC evaluation in breast cancer. (Pubitemid 39095313)
13. Cristofanilli M, Hayes DF, Budd GT et al. Circulating tumor cells: A novel prognostic factor for newly diagnosed metastatic breast cancer. J. Clin. Oncol. 23(7), 1420-1430 (2005).
14. Cristofanilli M, Broglio KR, Guarneri V et al. Circulating tumor cells in metastatic breast cancer: Biologic staging beyond tumor burden. Clin. Breast Cancer 7(6), 471-479 (2007). (Pubitemid 46424284)
15. Hayes DF, Cristofanilli M, Budd GT et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin. Cancer Res. 12(14 Pt 1), 4218-4224 (2006).
16. Budd GT, Cristofanilli M, Ellis MJ et al. Circulating tumor cells versus imaging - predicting overall survival in metastatic breast cancer. Clin. Cancer Res. 12(21), 6403-6409 (2006). .. CTCs were found to be significantly more reproducible than radiographic imaging in a comparison study. (Pubitemid 44799711)
17. Liotta LA, Stetler-Stevenson WG. Tumor invasion and metastasis: An imbalance of positive and negative regulation. Cancer Res. 51(Suppl. 18), S5054-S5059 (1991).
18. Lu J, Fan T, Zhao Q et al. Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients. Int. J. Cancer 126(3), 669-683 (2010).
19. Aktas B, Tewes M, Fehm T et al. Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 11(4), R46 (2009).
20. Gazzaniga P, Naso G, Gradilone A et al. Chemosensitivity profile assay of circulating cancer cells: Prognostic and predictive value in epithelial tumors. Int. J. Cancer 126(10), 2437-2447 (2010).
21. Meng S, Tripathy D, Frenkel EP et al. Circulating tumor cells in patients with breast cancer dormancy. Clin. Cancer Res. 10(24), 8152-8162 (2004). (Pubitemid 40053373)
22. Lianidou ES, Markou A. Circulating tumor cells in breast cancer: Detection systems, molecular characterization, and future challenges. Clin. Chem. 57(9), 1242-1255 (2011).
23. Lianidou ES, Markou A. Circulating tumor cells as emerging tumor biomarkers in breast cancer. Clin. Chem. Lab. Med. 49(10), 1579-1590 (2011).
24. Ghossein RA, Bhattacharya S, Rosai J. Molecular detection of micrometastases and circulating tumor cells in solid tumors. Clin. Cancer Res. 5(8), 1950-1960 (1999). (Pubitemid 29399243)
25. Ross AA, Cooper BW, Lazarus HM et al. Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques. Blood 82(9), 2605-2610 (1993). (Pubitemid 23318065)
26. Lin HK, Zheng S, Williams AJ et al. Portable filter-based microdevice for detection and characterization of circulating tumor cells. Clin. Cancer Res. 16, 5011-5018 (2010).
27. Willipinski-Stapelfeldt B, Riethdorf S, Assmann V et al. Changes in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells. Clin. Cancer Res. 11(22), 8006-8014 (2005). (Pubitemid 41698741)
28. Nagrath S, Sequist LV, Maheswaran S et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173), 1235-1239 (2007).
29. Alix-Panabiéres C, Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Clin. Cancer Res. 14(16), 5013-5021 (2008).
30. Vona G, Sabile A, Louha M et al. Isolation by size of epithelial tumor cells: A new method for the immunomorphological and molecular characterization of circulating tumor cells. Am. J. Pathol. 156(1), 57-63 (2000). (Pubitemid 30644439)
31. Witzig TE, Bossy B, Kimlinger T et al. Detection of circulating cytokeratin-positive cells in the blood of breast cancer patients using immunomagnetic enrichment and digital microscopy. Clin. Cancer Res. 8(5), 1085-1091 (2002). (Pubitemid 34517644)
32. Harris L, Fritsche H, Mennel R et al.; American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J. Clin. Oncol. 25(33), 5287-5312 (2007). (Pubitemid 350232263)
33. Nolé F, Munzone E, Zorzino L et al. Variation of circulating tumor cell levels during treatment of metastatic breast cancer: Prognostic and therapeutic implications. Ann. Oncol. 19(5), 891-897 (2008). (Pubitemid 351627303)
34. Riethdorf S, Fritsche H, Müller V et al. 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(3), 920-928 (2007). (Pubitemid 46340368)
35. Bustin SA, Mueller R. Real-time reverse transcription PCR (qRT-PCR) and its potential use in clinical diagnosis. Clin. Sci. (Lond.) 109(4), 365-379 (2005). (Pubitemid 41445244)
36. Chelly J, Concordet JP, Kaplan JC et al. Illegitimate transcription: Transcription of any gene in any cell type. Proc. Natl Acad. Sci. USA 86(8), 2617-2621 (1989). (Pubitemid 19112598)
37. Ring AE, Zabaglo L, Ormerod MG et al. Detection of circulating epithelial cells in the blood of patients with breast cancer: Comparison of three techniques. Br. J. Cancer 92(5), 906-912 (2005). (Pubitemid 40462638)
38. Shen C, Hu L, Xia L et al. The detection of circulating tumor cells of breast cancer patients by using multimarker (survivin, hTERT and hMAM) quantitative real-time PCR. Clin. Biochem. 42(3), 194-200 (2009).
39. Sieuwerts AM, Kraan J, Bolt-de Vries J et al. Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR. Breast Cancer Res. Treat. 118(3), 455-468 (2009).
40. Punnoose EA, Atwal SK, Spoerke JM et al. Molecular biomarker analyses using circulating tumor cells. PLoS One 5(9), e12517 (2010).
41. Andreopoulou E, Yang LY, Rangel KM et al. Comparison of assay methods for detection of circulating tumor cells (CTCs) in metastatic breast cancer (MBC): AdnaGen AdnaTest BreastCancer Select/Detect™ versus Veridex CellSerach™ System. Int. J. Cancer doi:10.1002/ijc.26111 (2011) (Epub ahead of print).
42. Fehm T, Müller V, Aktas B et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: A prospective, multicenter trial. Breast Cancer Res. Treat. 124(2), 403-412 (2010).
43. Riethdorf S, Müller V, Zhang L et al. 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 (2010). .. Largest assessment regarding neoadjuvant trials showing no significant correlation between CTC detection and tumor response.
44. Pierga JY, Bidard FC, Mathiot C et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a Phase II randomized trial. Clin. Cancer Res. 14(21), 7004-7010 (2008).
45. Bidard FC, Mathiot C, Delaloge S et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann. Oncol. 21(4), 729-733 (2010).
46. García-Sáenz JA, Martín M, Maestro ML et al. Circulating tumour cells in locally advanced breast cancer. Clin. Transl. Oncol. 11(8), 544-547 (2009).
47. Lang JE, Mosalpuria K, Cristofanilli M et al. HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer. Breast Cancer Res. Treat. 113(3), 501-507 (2009).
48. Zach O, Kasparu H, Wagner H et al. Prognostic value of tumour cell detection in peripheral blood of breast cancer patients. Acta Med. Austriaca. Suppl. 59, 32-34 (2002).
49. Stathopoulou A, Vlachonikolis I, Mavroudis D 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. 20(16), 3404-3412 (2002). . Prospective evidence clearly supported a significant prognostic role of CK19 mRNA-positive CTCs.
50. Xenidis N, Perraki M, Kafousi M et al. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J. Clin. Oncol. 24(23), 3756-3762 (2006). (Pubitemid 46622314)
51. Apostolaki S, Perraki M, Pallis A et al. 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 (2007). (Pubitemid 47054081)
52. Pachmann K, Camara O, Kavallaris A et al. 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. 26(8), 1208-1215 (2008).
53. De Giorgi U, Valero V, Rohren E et al. Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. Ann. Oncol. 21(1), 33-39 (2010).
54. Gancberg D, Di Leo A, Cardoso F et al. Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann. Oncol. 13(7), 1036-1043 (2002).
55. Shimizu C, Fukutomi T, Tsuda H et al. c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues. J. Surg. Oncol. 73(1), 17-20 (2000). (Pubitemid 30067528)
56. Gradilone A, Naso G, Raimondi C et al. Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): Prognosis, drug resistance and phenotypic characterization. Ann. Oncol. 22(1), 86-92 (2011).
57. Santinelli A, Pisa E, Stramazzotti D et al. HER-2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy. Int. J. Cancer 122(5), 999-1004 (2008). (Pubitemid 351213996)
58. Hayes DF, Walker TM, Singh B et al. Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int. J. Oncol. 21(5), 1111-1117 (2002).
59. Wülfing P, Borchard J, Buerger H et al. HER2 positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin. Cancer Res. 12(6), 1715-1720 (2006).
60. Munzone E, Nolé F, Goldhirsch A et al. Changes of HER2 status in circulating tumor cells compared with the primary tumor during treatment for advanced breast cancer. Clin. Breast Cancer. 10(5), 392-397 (2010).
61. Meng S, Tripathy D, Shete S et al. HER2 gene amplification can be acquired as breast cancer progresses. Proc. Natl Acad. Sci. USA 101(25), 9393-9398 (2004). (Pubitemid 38812885)
62. Flores LM, Kindelberger DW, Ligon AH et al. Improving the yield of circulating tumour cells facilitates molecular characterization and recognition of discordant HER2 amplification in breast cancer. Br. J. Cancer. 102(10), 1495-1502 (2010).
63. Somlo G, Lau SK, Frankel P et al. Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology. Breast Cancer Res. Treat. 128(1), 155-163 (2011).
64. Smirnov DA, Zweitzig DR, Foulk BW et al. Global gene expression profiling of circulating tumor cells. Cancer Res. 65, 4993-4997 (2005). (Pubitemid 40827303)
65. Reuben JM. Oral communication. Presented at: San Antonio Breast Cancer Symposium. San Antonio, TX, USA, 6-10 December (2008).
66. Fonseca FL, Soares HP, Manhani AR et al. Peripheral blood c-erbB-2 expression by reverse transcriptase-polymerase chain reaction in breast cancer patients receiving chemotherapy. Clin. Breast Cancer 3(3), 201-205 (2002).
67. Kallergi G, Markomanolaki H, Giannoukaraki V et al. Hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients. Breast Cancer Res. 11(6), R84 (2009).
68. Kallergi G, Agelaki S, Kalykaki A et al. Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients. Breast Cancer Res. 10(5), R80 (2008).
69. Ashworth TR. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust. Med. J. 14, 146-149 (1869).
70. Sieuwerts AM, Kraan J, Bolt J et al. Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. J. Natl Cancer Inst. 101(1), 61-66 (2009). . Pointed out a limit of the CellSearch® system - that it did not recognize 'normal' breast cancer cells.
71. Pusztai L, Viale G, Kelly CM, Hudis CA. Estrogen and HER-2 receptor discordance between primary breast cancer and metastasis. Oncologist 15(11), 1164-1168 (2010).
72. Pachmann K, Camara O, Kohlhase A et al. Assessing the efficacy of targeted therapy using circulating epithelial tumor cells (CETC): The example of SERM therapy monitoring as a unique tool to individualize therapy. J. Cancer Res. Clin. Oncol. 137(5), 821-828 (2011).
73. Xenidis N, Markos V, Apostolaki S et al. Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer. Ann. Oncol. 18(10), 1623-1631 (2007). (Pubitemid 47506248)
74. Sieuwerts AM, Mostert B, Bolt-de Vries J et al. mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin. Cancer Res. 17(11), 3600-3618 (2011).
75. Obermayr E, Sanchez-Cabo F, Tea MK et al. Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients. BMC Cancer 3(10), 666 (2010).
76. Tewes M, Aktas B, Welt A et al. 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), 581-590 (2009).