Skip to main content
Top
Published in: Breast Cancer Research 5/2014

Open Access 01-10-2014 | Research article

Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination

Authors: Mario Giuliano, Antonio Giordano, Summer Jackson, Ugo De Giorgi, Michal Mego, Evan N Cohen, Hui Gao, Simone Anfossi, Beverly C Handy, Naoto T Ueno, Ricardo H Alvarez, Sabino De Placido, Vicente Valero, Gabriel N Hortobagyi, James M Reuben, Massimo Cristofanilli

Published in: Breast Cancer Research | Issue 5/2014

Login to get access

Abstract

Introduction

Traditional factors currently used for prognostic stratification do not always adequately predict treatment response and disease evolution in advanced breast cancer patients. Therefore, the use of blood-based markers, such as circulating tumor cells (CTCs), represents a promising complementary strategy for disease monitoring. In this retrospective study, we explored the role of CTC counts as predictors of disease evolution in breast cancer patients with limited metastatic dissemination.

Methods

A total of 492 advanced breast cancer patients who had a CTC count assessed by CellSearch prior to starting a new line of systemic therapy were eligible for this analysis. Using the threshold of 5 CTCs/7.5 ml of blood, pretreatment CTC counts were correlated in the overall population with metastatic site distribution, evaluated at baseline and at the time of treatment failure, using Fisher’s exact test. Time to visceral progression and time to the development of new metastatic lesions and sites were estimated in patients with nonvisceral metastases and with single-site metastatic disease, respectively, by the Kaplan-Meier method. Survival times were compared between groups according to pretreatment CTC count by logrank test.

Results

In the overall population, a pretreatment level ≥5 CTCs/7.5 ml was associated with an increased baseline number of metastatic sites compared with <5 CTCs/7.5 ml (P = 0.0077). At the time of treatment failure, patients with ≥5 CTCs/7.5 ml more frequently developed new metastatic lesions and sites compared with those with <5 CTCs/7.5 ml (development of new lesions: P = 0.0002; development of new sites: P = 0.0031). Among patients with disease originally confined to nonvisceral sites, ≥5 CTCs/7.5 ml was associated with remarkably shorter time to visceral metastases (P = 0.0021) and overall survival (P = 0.0006) compared with <5 CTCs/7.5 ml. In patients with single-site metastatic disease, ≥5 CTCs/7.5 ml was associated with a significant reduction of the time to development of new metastatic sites (P = 0.0051) and new lesions (P = 0.0002) and with worse overall survival (P = 0.0101).

Conclusion

Our results suggest that baseline CTC counts can be used as an early predictor of metastatic potential in breast cancer patients with limited metastatic dissemination.
Appendix
Available only for authorised users
Literature
1.
go back to reference Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (Eds): SEER Cancer Statistics Review, 1975-2010. Bethesda, MD: National Cancer Institute; , based on November 2012 SEER data submission, posted to the SEER web site, April 2013., [http://seer.cancer.gov/csr/1975_2010/] Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (Eds): SEER Cancer Statistics Review, 1975-2010. Bethesda, MD: National Cancer Institute; , based on November 2012 SEER data submission, posted to the SEER web site, April 2013., [http://​seer.​cancer.​gov/​csr/​1975_​2010/​]
2.
go back to reference Yardley DA: Visceral disease in patients with metastatic breast cancer: efficacy and safety of treatment with ixabepilone and other chemotherapeutic agents. Clin Breast Cancer. 2010, 10: 64-73. 10.3816/CBC.2010.n.009.CrossRefPubMed Yardley DA: Visceral disease in patients with metastatic breast cancer: efficacy and safety of treatment with ixabepilone and other chemotherapeutic agents. Clin Breast Cancer. 2010, 10: 64-73. 10.3816/CBC.2010.n.009.CrossRefPubMed
3.
go back to reference Alunni-Fabbroni M, Müller V, Fehm T, Janni W, Rack B: Monitoring in metastatic breast cancer: is imaging outdated in the era of circulating tumor cells?. Breast Care. 2014, 9: 16-21. 10.1159/000360438.CrossRefPubMedPubMedCentral Alunni-Fabbroni M, Müller V, Fehm T, Janni W, Rack B: Monitoring in metastatic breast cancer: is imaging outdated in the era of circulating tumor cells?. Breast Care. 2014, 9: 16-21. 10.1159/000360438.CrossRefPubMedPubMedCentral
4.
go back to reference Alix-Panabières C, Pantel K: Technologies for detection of circulating tumor cells: facts and vision. Lab Chip. 2014, 14: 57-62. 10.1039/c3lc50644d.CrossRefPubMed Alix-Panabières C, Pantel K: Technologies for detection of circulating tumor cells: facts and vision. Lab Chip. 2014, 14: 57-62. 10.1039/c3lc50644d.CrossRefPubMed
5.
go back to reference Esmaeilsabzali H, Beischlag TV, Cox ME, Parameswaran AM, Park EJ: Detection and isolation of circulating tumor cells: principles and methods. Biotechnol Adv. 2013, 31: 1063-1084. 10.1016/j.biotechadv.2013.08.016.CrossRefPubMed Esmaeilsabzali H, Beischlag TV, Cox ME, Parameswaran AM, Park EJ: Detection and isolation of circulating tumor cells: principles and methods. Biotechnol Adv. 2013, 31: 1063-1084. 10.1016/j.biotechadv.2013.08.016.CrossRefPubMed
6.
go back to reference Pantel K, Alix-Panabières C, Riethdorf S: Cancer micrometastases. Nat Rev Clin Oncol. 2009, 6: 339-351. 10.1038/nrclinonc.2009.44.CrossRefPubMed Pantel K, Alix-Panabières C, Riethdorf S: Cancer micrometastases. Nat Rev Clin Oncol. 2009, 6: 339-351. 10.1038/nrclinonc.2009.44.CrossRefPubMed
7.
go back to reference Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004, 351: 781-791. 10.1056/NEJMoa040766.CrossRefPubMed Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004, 351: 781-791. 10.1056/NEJMoa040766.CrossRefPubMed
8.
go back to reference Giordano A, Giuliano M, De Laurentiis M, Arpino G, Jackson S, Handy BC, Ueno NT, Andreopoulou E, Alvarez RH, Valero V, De Placido S, Hortobagyi GN, Reuben JM, Cristofanilli M: Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: lack of prediction in HER2-positive disease treated with targeted therapy. Ann Oncol. 2012, 23: 1144-1150. 10.1093/annonc/mdr434.CrossRefPubMed Giordano A, Giuliano M, De Laurentiis M, Arpino G, Jackson S, Handy BC, Ueno NT, Andreopoulou E, Alvarez RH, Valero V, De Placido S, Hortobagyi GN, Reuben JM, Cristofanilli M: Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: lack of prediction in HER2-positive disease treated with targeted therapy. Ann Oncol. 2012, 23: 1144-1150. 10.1093/annonc/mdr434.CrossRefPubMed
9.
go back to reference Giordano A, Egleston BL, Hajage D, Bland J, Hortobagyi GN, Reuben JM, Pierga JY, Cristofanilli M, Bidard FC: Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients. Clin Cancer Res. 2013, 19: 1596-1602. 10.1158/1078-0432.CCR-12-3137.CrossRefPubMedPubMedCentral Giordano A, Egleston BL, Hajage D, Bland J, Hortobagyi GN, Reuben JM, Pierga JY, Cristofanilli M, Bidard FC: Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients. Clin Cancer Res. 2013, 19: 1596-1602. 10.1158/1078-0432.CCR-12-3137.CrossRefPubMedPubMedCentral
10.
go back to reference Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, O’Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF: Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500.J Clin Oncol in press. doi:10.1200/JCO.2014.56.2561., Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, O’Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF: Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500.J Clin Oncol in press. doi:10.1200/JCO.2014.56.2561.,
11.
go back to reference Giuliano M, Giordano A, Jackson S, Hess KR, De Giorgi U, Mego M, Handy BC, Ueno NT, Alvarez RH, De Laurentiis M, De Placido S, Valero V, Hortobagyi GN, Reuben JM, Cristofanilli M: Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res. 2011, 13: R67-10.1186/bcr2907.CrossRefPubMedPubMedCentral Giuliano M, Giordano A, Jackson S, Hess KR, De Giorgi U, Mego M, Handy BC, Ueno NT, Alvarez RH, De Laurentiis M, De Placido S, Valero V, Hortobagyi GN, Reuben JM, Cristofanilli M: Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res. 2011, 13: R67-10.1186/bcr2907.CrossRefPubMedPubMedCentral
12.
go back to reference Hellman S, Weichselbaum RR: Oligometastases. J Clin Oncol. 1995, 13: 8-10.PubMed Hellman S, Weichselbaum RR: Oligometastases. J Clin Oncol. 1995, 13: 8-10.PubMed
13.
go back to reference Weichselbaum RR, Hellman S: Oligometastases revisited. Nat Rev Clin Oncol. 2011, 8: 378-382.PubMed Weichselbaum RR, Hellman S: Oligometastases revisited. Nat Rev Clin Oncol. 2011, 8: 378-382.PubMed
14.
go back to reference Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, Costa A, Winer EP, Cardoso F: International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured?. J Natl Cancer Inst. 2010, 102: 456-463. 10.1093/jnci/djq029.CrossRefPubMedPubMedCentral Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, Costa A, Winer EP, Cardoso F: International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured?. J Natl Cancer Inst. 2010, 102: 456-463. 10.1093/jnci/djq029.CrossRefPubMedPubMedCentral
15.
go back to reference Giordano A, Giuliano M, De Laurentiis M, Eleuteri A, Iorio F, Tagliaferri R, Hortobagyi GN, Pusztai L, De Placido S, Hess K, Cristofanilli M, Reuben JM: Artificial neural network analysis of circulating tumor cells in metastatic breast cancer patients. Breast Cancer Res Treat. 2011, 129: 451-458. 10.1007/s10549-011-1645-5.CrossRefPubMed Giordano A, Giuliano M, De Laurentiis M, Eleuteri A, Iorio F, Tagliaferri R, Hortobagyi GN, Pusztai L, De Placido S, Hess K, Cristofanilli M, Reuben JM: Artificial neural network analysis of circulating tumor cells in metastatic breast cancer patients. Breast Cancer Res Treat. 2011, 129: 451-458. 10.1007/s10549-011-1645-5.CrossRefPubMed
16.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009, 45: 228-247. 10.1016/j.ejca.2008.10.026.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009, 45: 228-247. 10.1016/j.ejca.2008.10.026.CrossRefPubMed
17.
go back to reference Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller MC, Fritsche HA, Hortobagyi GN, Terstappen LW: Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol. 2005, 23: 1420-1430. 10.1200/JCO.2005.08.140. A published erratum appears in J Clin Oncol 2005, 23:4808CrossRefPubMed Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller MC, Fritsche HA, Hortobagyi GN, Terstappen LW: Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol. 2005, 23: 1420-1430. 10.1200/JCO.2005.08.140. A published erratum appears in J Clin Oncol 2005, 23:4808CrossRefPubMed
18.
go back to reference De Giorgi U, Valero V, Rohren E, Mego M, Doyle GV, Miller MC, Ueno NT, Handy BC, Reuben JM, Macapinlac HA, Hortobagyi GN, Cristofanilli M: Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. Ann Oncol. 2010, 21: 33-39. 10.1093/annonc/mdp262.CrossRefPubMed De Giorgi U, Valero V, Rohren E, Mego M, Doyle GV, Miller MC, Ueno NT, Handy BC, Reuben JM, Macapinlac HA, Hortobagyi GN, Cristofanilli M: Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. Ann Oncol. 2010, 21: 33-39. 10.1093/annonc/mdp262.CrossRefPubMed
19.
go back to reference Dong X, Alpaugh KR, Cristofanilli M: Circulating tumor cells (CTCs) in breast cancer: a diagnostic tool for prognosis and molecular analysis. Chin J Cancer Res. 2012, 24: 388-398. 10.1007/s11670-012-0279-4.CrossRefPubMedPubMedCentral Dong X, Alpaugh KR, Cristofanilli M: Circulating tumor cells (CTCs) in breast cancer: a diagnostic tool for prognosis and molecular analysis. Chin J Cancer Res. 2012, 24: 388-398. 10.1007/s11670-012-0279-4.CrossRefPubMedPubMedCentral
20.
go back to reference Parkinson DR, Dracopoli N, Petty BG, Compton C, Cristofanilli M, Deisseroth A, Hayes DF, Kapke G, Kumar P, Lee J, Liu MC, McCormack R, Mikulski S, Nagahara L, Pantel K, Pearson-White S, Punnoose EA, Roadcap LT, Schade AE, Scher HI, Sigman CC, Kelloff GJ: Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med. 2012, 10: 138-10.1186/1479-5876-10-138.CrossRefPubMedPubMedCentral Parkinson DR, Dracopoli N, Petty BG, Compton C, Cristofanilli M, Deisseroth A, Hayes DF, Kapke G, Kumar P, Lee J, Liu MC, McCormack R, Mikulski S, Nagahara L, Pantel K, Pearson-White S, Punnoose EA, Roadcap LT, Schade AE, Scher HI, Sigman CC, Kelloff GJ: Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med. 2012, 10: 138-10.1186/1479-5876-10-138.CrossRefPubMedPubMedCentral
21.
go back to reference Budd GT, Cristofanilli M, Ellis MJ, Stopeck A, Borden E, Miller MC, Matera J, Repollet M, Doyle GV, Terstappen LWMM, Hayes DF: Circulating tumor cells versus imaging—predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006, 12: 6403-6409. 10.1158/1078-0432.CCR-05-1769.CrossRefPubMed Budd GT, Cristofanilli M, Ellis MJ, Stopeck A, Borden E, Miller MC, Matera J, Repollet M, Doyle GV, Terstappen LWMM, Hayes DF: Circulating tumor cells versus imaging—predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006, 12: 6403-6409. 10.1158/1078-0432.CCR-05-1769.CrossRefPubMed
22.
go back to reference Liu MC, Shields PG, Warren RD, Cohen P, Wilkinson M, Ottaviano YL, Rao SB, Eng-Wong J, Seillier-Moiseiwitsch F, Noone AM, Isaacs C: Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009, 27: 5153-5159. 10.1200/JCO.2008.20.6664.CrossRefPubMedPubMedCentral Liu MC, Shields PG, Warren RD, Cohen P, Wilkinson M, Ottaviano YL, Rao SB, Eng-Wong J, Seillier-Moiseiwitsch F, Noone AM, Isaacs C: Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009, 27: 5153-5159. 10.1200/JCO.2008.20.6664.CrossRefPubMedPubMedCentral
23.
go back to reference Hayes DF, Smerage J: Is there a role for circulating tumor cells in the management of breast cancer?. Clin Cancer Res. 2008, 14: 3646-3650. 10.1158/1078-0432.CCR-07-4481.CrossRefPubMed Hayes DF, Smerage J: Is there a role for circulating tumor cells in the management of breast cancer?. Clin Cancer Res. 2008, 14: 3646-3650. 10.1158/1078-0432.CCR-07-4481.CrossRefPubMed
24.
go back to reference Bidard FC, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Lebofsky R, van Laere SJ, Meier-Stiegen F, Sandri MT, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson SJ, Raimondi C, Rutten A, et al: Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014, 15: 406-414. 10.1016/S1470-2045(14)70069-5.CrossRefPubMed Bidard FC, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Lebofsky R, van Laere SJ, Meier-Stiegen F, Sandri MT, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson SJ, Raimondi C, Rutten A, et al: Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014, 15: 406-414. 10.1016/S1470-2045(14)70069-5.CrossRefPubMed
25.
go back to reference Wilcken N, Hornbuckle J, Ghersi D: Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer.Cochrane Database Syst Rev 2003, (2):CD002747., Wilcken N, Hornbuckle J, Ghersi D: Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer.Cochrane Database Syst Rev 2003, (2):CD002747.,
26.
go back to reference Cardoso F, Costa A, Norton L, Cameron D, Cufer T, Fallowfield L, Francis P, Gligorov J, Kyriakides S, Lin N, Pagani O, Senkus E, Thomssen C, Aapro M, Bergh J, Di Leo A, El Saghir N, Ganz PA, Gelmon K, Goldhirsch A, Harbeck N, Houssami N, Hudis C, Kaufman B, Leadbeater M, Mayer M, Rodger A, Rugo H, Sacchini V, Sledge G, et al: 1st international consensus guidelines for advanced breast cancer (ABC 1). Breast. 2012, 21: 242-252. 10.1016/j.breast.2012.03.003.CrossRefPubMed Cardoso F, Costa A, Norton L, Cameron D, Cufer T, Fallowfield L, Francis P, Gligorov J, Kyriakides S, Lin N, Pagani O, Senkus E, Thomssen C, Aapro M, Bergh J, Di Leo A, El Saghir N, Ganz PA, Gelmon K, Goldhirsch A, Harbeck N, Houssami N, Hudis C, Kaufman B, Leadbeater M, Mayer M, Rodger A, Rugo H, Sacchini V, Sledge G, et al: 1st international consensus guidelines for advanced breast cancer (ABC 1). Breast. 2012, 21: 242-252. 10.1016/j.breast.2012.03.003.CrossRefPubMed
27.
go back to reference Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Stojanov P, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, Haber DA: Cancer therapy: ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science. 2014, 345: 216-220. 10.1126/science.1253533.CrossRefPubMedPubMedCentral Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Stojanov P, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, Haber DA: Cancer therapy: ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science. 2014, 345: 216-220. 10.1126/science.1253533.CrossRefPubMedPubMedCentral
28.
go back to reference Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, Guan JL, Dontu G, Wicha MS: CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 2010, 120: 485-497. 10.1172/JCI39397.CrossRefPubMedPubMedCentral Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, Guan JL, Dontu G, Wicha MS: CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 2010, 120: 485-497. 10.1172/JCI39397.CrossRefPubMedPubMedCentral
29.
go back to reference Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S: Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 2009, 11: R46-10.1186/bcr2333.CrossRefPubMedPubMedCentral Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S: Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 2009, 11: R46-10.1186/bcr2333.CrossRefPubMedPubMedCentral
30.
go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133: 704-715. 10.1016/j.cell.2008.03.027.CrossRefPubMedPubMedCentral Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133: 704-715. 10.1016/j.cell.2008.03.027.CrossRefPubMedPubMedCentral
31.
go back to reference Guarino M, Rubino B, Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007, 39: 305-318. 10.1080/00313020701329914.CrossRefPubMed Guarino M, Rubino B, Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007, 39: 305-318. 10.1080/00313020701329914.CrossRefPubMed
32.
go back to reference Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S: Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013, 339: 580-584. 10.1126/science.1228522.CrossRefPubMedPubMedCentral Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S: Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013, 339: 580-584. 10.1126/science.1228522.CrossRefPubMedPubMedCentral
33.
go back to reference Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN, Tin S, De Laurentiis M, Parker CA, Alvarez RH, Valero V, Ueno NT, De Placido S, Mani SA, Esteva FJ, Cristofanilli M, Reuben JM: Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther. 2012, 11: 2526-2534. 10.1158/1535-7163.MCT-12-0460.CrossRefPubMedPubMedCentral Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN, Tin S, De Laurentiis M, Parker CA, Alvarez RH, Valero V, Ueno NT, De Placido S, Mani SA, Esteva FJ, Cristofanilli M, Reuben JM: Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther. 2012, 11: 2526-2534. 10.1158/1535-7163.MCT-12-0460.CrossRefPubMedPubMedCentral
34.
go back to reference Mego M, Gao H, Lee BN, Cohen EN, Tin S, Giordano A, Wu Q, Liu P, Nieto Y, Champlin RE, Hortobagyi GN, Cristofanilli M, Ueno NT, Reuben JM: Prognostic value of EMT-circulating tumor cells in metastatic breast cancer patients undergoing high-dose chemotherapy with autologous hematopoietic stem cell transplantation. J Cancer. 2012, 3: 369-380. 10.7150/jca.5111.CrossRefPubMedPubMedCentral Mego M, Gao H, Lee BN, Cohen EN, Tin S, Giordano A, Wu Q, Liu P, Nieto Y, Champlin RE, Hortobagyi GN, Cristofanilli M, Ueno NT, Reuben JM: Prognostic value of EMT-circulating tumor cells in metastatic breast cancer patients undergoing high-dose chemotherapy with autologous hematopoietic stem cell transplantation. J Cancer. 2012, 3: 369-380. 10.7150/jca.5111.CrossRefPubMedPubMedCentral
35.
go back to reference Liu H, Zhang X, Li J, Sun B, Qian H, Yin Z: The biological and clinical importance of epithelial-mesenchymal transition in circulating tumor cells.J Cancer Res Clin Oncol in press. doi:10.1007/s00432-014-1752-x., Liu H, Zhang X, Li J, Sun B, Qian H, Yin Z: The biological and clinical importance of epithelial-mesenchymal transition in circulating tumor cells.J Cancer Res Clin Oncol in press. doi:10.1007/s00432-014-1752-x.,
36.
go back to reference Grover PK, Cummins AG, Price TJ, Roberts-Thomson IC, Hardingham JE: Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Ann Oncol. 2014, 25: 1506-1516. 10.1093/annonc/mdu018.CrossRefPubMed Grover PK, Cummins AG, Price TJ, Roberts-Thomson IC, Hardingham JE: Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Ann Oncol. 2014, 25: 1506-1516. 10.1093/annonc/mdu018.CrossRefPubMed
37.
go back to reference Sieuwerts AM, Kraan J, Bolt J, van der Spoel P, Elstrodt F, Schutte M, Martens JW, Gratama JW, Sleijfer S, Foekens JA: Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. J Natl Cancer Inst. 2009, 101: 61-66. 10.1093/jnci/djn419.CrossRefPubMedPubMedCentral Sieuwerts AM, Kraan J, Bolt J, van der Spoel P, Elstrodt F, Schutte M, Martens JW, Gratama JW, Sleijfer S, Foekens JA: Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. J Natl Cancer Inst. 2009, 101: 61-66. 10.1093/jnci/djn419.CrossRefPubMedPubMedCentral
Metadata
Title
Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination
Authors
Mario Giuliano
Antonio Giordano
Summer Jackson
Ugo De Giorgi
Michal Mego
Evan N Cohen
Hui Gao
Simone Anfossi
Beverly C Handy
Naoto T Ueno
Ricardo H Alvarez
Sabino De Placido
Vicente Valero
Gabriel N Hortobagyi
James M Reuben
Massimo Cristofanilli
Publication date
01-10-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-014-0440-8

Other articles of this Issue 5/2014

Breast Cancer Research 5/2014 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