Skip to main content
Top
Published in: Medical Oncology 10/2019

01-10-2019 | Breast Cancer | Short Communication

Impact of circulating tumour cells on survival of eribulin-treated patients with metastatic breast cancer

Authors: Mayuko Ito, Yoshiya Horimoto, Emi Tokuda, Fumi Murakami, Toshitaka Uomori, Takanori Himuro, Katsuya Nakai, Gotaro Orihata, Kotaro Iijima, Mitsue Saito

Published in: Medical Oncology | Issue 10/2019

Login to get access

Abstract

Several clinical studies have examined circulating tumour cells (CTCs). However, the application of CTCs as a predictive/prognostic marker for breast cancer patients has yet to be established, particularly the selection of suitable markers for detecting CTCs. We recently investigated CTCs, including mesenchymal status, from metastatic breast cancer patients who had received eribulin-based treatment. We found that assessment of both mesenchymal and epithelial CTCs might be important for predicting eribulin responsiveness. In the current study, we followed up the outcomes of these patients after eribulin treatment and investigated the possibility of CTC analysis results serving as prognostic markers for this patient population. Twenty-one patients were enrolled and peripheral blood samples were collected before eribulin-based treatments. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Overall survival (OS) was assessed in relation to the number of CTCs and clinicopathological factors. During the observation period, 13 patients (62%) died due to breast cancer and the median OS was 18 months. Patients with high-grade tumours and a high total number of CTCs showed significantly shorter OS than those with low-grade tumours and smaller CTC burdens (p = 0.026 and 0.037, respectively). Patients who received eribulin as the first chemotherapy for metastatic disease showed longer OS (p = 0.006). Our data suggest that determining numbers of both mesenchymal and epithelial CTCs might predict survival for patients receiving eribulin.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bidard F-C, 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 M-T, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson S-J, Raimondi C, Rutten A, Janni W, Munzone E, Carañana V, Agelaki S, Almici C, Dirix L, Solomayer E-F, Zorzino L, Johannes H, Reis-Filho JS, Pantel K, Pierga J-Y, Michiels S. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014;15:406–14.CrossRef Bidard F-C, 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 M-T, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson S-J, Raimondi C, Rutten A, Janni W, Munzone E, Carañana V, Agelaki S, Almici C, Dirix L, Solomayer E-F, Zorzino L, Johannes H, Reis-Filho JS, Pantel K, Pierga J-Y, Michiels S. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014;15:406–14.CrossRef
2.
go back to reference Bidard F-C, Michiels S, Riethdorf S, Mueller V, Esserman LJ, Lucci A, Naume B, Horiguchi J, Gisbert-Criado R, Sleijfer S, Toi M, Garcia-Saenz JA, Hartkopf A, Generali D, Rothé F, Smerage J, Muinelo-Romay L, Stebbing J, Viens P, Magbanua MJM, Hall CS, Engebraaten O, Takata D, Vidal-Martínez J, Onstenk W, Fujisawa N, Diaz-Rubio E, Taran F-A, Cappelletti MR, Ignatiadis M, Proudhon C, Wolf DM, Bauldry JB, Borgen E, Nagaoka R, Carañana V, Kraan J, Maestro M, Brucker SY, Weber K, Reyal F, Amara D, Karhade MG, Mathiesen RR, Tokiniwa H, Llombart-Cussac A, Meddis A, Blanche P, d’Hollander K, Cottu P, Park JW, Loibl S, Latouche A, Pierga J-Y, Pantel K. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst. 2018;110:560–7.CrossRef Bidard F-C, Michiels S, Riethdorf S, Mueller V, Esserman LJ, Lucci A, Naume B, Horiguchi J, Gisbert-Criado R, Sleijfer S, Toi M, Garcia-Saenz JA, Hartkopf A, Generali D, Rothé F, Smerage J, Muinelo-Romay L, Stebbing J, Viens P, Magbanua MJM, Hall CS, Engebraaten O, Takata D, Vidal-Martínez J, Onstenk W, Fujisawa N, Diaz-Rubio E, Taran F-A, Cappelletti MR, Ignatiadis M, Proudhon C, Wolf DM, Bauldry JB, Borgen E, Nagaoka R, Carañana V, Kraan J, Maestro M, Brucker SY, Weber K, Reyal F, Amara D, Karhade MG, Mathiesen RR, Tokiniwa H, Llombart-Cussac A, Meddis A, Blanche P, d’Hollander K, Cottu P, Park JW, Loibl S, Latouche A, Pierga J-Y, Pantel K. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst. 2018;110:560–7.CrossRef
3.
go back to reference Rossi G, Mu Z, Rademaker AW, Austin LK, Strickland KS, Costa RLB, Nagy RJ, Zagonel V, Taxter TJ, Behdad A, Wehbe FH, Platanias LC, Gradishar WJ, Cristofanilli M. Cell-free DNA and circulating tumor cells: comprehensive liquid biopsy analysis in advanced breast cancer. Clin Cancer Res. 2018;24:560–8.CrossRef Rossi G, Mu Z, Rademaker AW, Austin LK, Strickland KS, Costa RLB, Nagy RJ, Zagonel V, Taxter TJ, Behdad A, Wehbe FH, Platanias LC, Gradishar WJ, Cristofanilli M. Cell-free DNA and circulating tumor cells: comprehensive liquid biopsy analysis in advanced breast cancer. Clin Cancer Res. 2018;24:560–8.CrossRef
4.
go back to reference Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AGJ, Uhr JW, Terstappen LWMM. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897–904.CrossRef Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AGJ, Uhr JW, Terstappen LWMM. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897–904.CrossRef
5.
go back to reference Gorges TM, Tinhofer I, Drosch M, Röse L, Zollner TM, Krahn T. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer. 2012;12:178.CrossRef Gorges TM, Tinhofer I, Drosch M, Röse L, Zollner TM, Krahn T. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer. 2012;12:178.CrossRef
6.
go back to reference Königsberg R, Obermayr E, Bises G, Pfeiler G, Gneist M, Wrba F, de Santis M, Zeillinger R, Hudec M, Dittrich C. Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients. Acta Oncol. 2011;50:700–10.CrossRef Königsberg R, Obermayr E, Bises G, Pfeiler G, Gneist M, Wrba F, de Santis M, Zeillinger R, Hudec M, Dittrich C. Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients. Acta Oncol. 2011;50:700–10.CrossRef
7.
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 (New York, NY). 2013;339:580–4.CrossRef 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 (New York, NY). 2013;339:580–4.CrossRef
8.
go back to reference Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, Herold CI, Marcom PK, George DJ, Garcia-Blanco MA. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res. 2011;9:997–1007.CrossRef Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, Herold CI, Marcom PK, George DJ, Garcia-Blanco MA. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res. 2011;9:997–1007.CrossRef
9.
go back to reference Mego M, Cierna Z, Janega P, Karaba M, Minarik G, Benca J, Sedlácková T, Sieberova G, Gronesova P, Manasova D, Pindak D, Sufliarsky J, Danihel L, Reuben JM, Mardiak J. Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer. BMC Cancer. 2015;15:533.CrossRef Mego M, Cierna Z, Janega P, Karaba M, Minarik G, Benca J, Sedlácková T, Sieberova G, Gronesova P, Manasova D, Pindak D, Sufliarsky J, Danihel L, Reuben JM, Mardiak J. Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer. BMC Cancer. 2015;15:533.CrossRef
10.
go back to reference Polioudaki H, Agelaki S, Chiotaki R, Politaki E, Mavroudis D, Matikas A, Georgoulias V, Theodoropoulos PA. Variable expression levels of keratin and vimentin reveal differential EMT status of circulating tumor cells and correlation with clinical characteristics and outcome of patients with metastatic breast cancer. BMC Cancer. 2015;15:399.CrossRef Polioudaki H, Agelaki S, Chiotaki R, Politaki E, Mavroudis D, Matikas A, Georgoulias V, Theodoropoulos PA. Variable expression levels of keratin and vimentin reveal differential EMT status of circulating tumor cells and correlation with clinical characteristics and outcome of patients with metastatic breast cancer. BMC Cancer. 2015;15:399.CrossRef
11.
go back to reference Hyun K-A, Koo G-B, Han H, Sohn J, Choi W, Kim S-I, Jung H-I, Kim Y-S. Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Oncotarget. 2016;7:24677–87.CrossRef Hyun K-A, Koo G-B, Han H, Sohn J, Choi W, Kim S-I, Jung H-I, Kim Y-S. Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Oncotarget. 2016;7:24677–87.CrossRef
12.
go back to reference Gogoi P, Sepehri S, Zhou Y, Gorin MA, Paolillo C, Capoluongo E, Gleason K, Payne A, Boniface B, Cristofanilli M, Morgan TM, Fortina P, Pienta KJ, Handique K, Wang Y. Development of an automated and sensitive microfluidic device for capturing and characterizing circulating tumor cells (CTCs) from clinical blood samples. PLoS ONE. 2016;11:e0147400.CrossRef Gogoi P, Sepehri S, Zhou Y, Gorin MA, Paolillo C, Capoluongo E, Gleason K, Payne A, Boniface B, Cristofanilli M, Morgan TM, Fortina P, Pienta KJ, Handique K, Wang Y. Development of an automated and sensitive microfluidic device for capturing and characterizing circulating tumor cells (CTCs) from clinical blood samples. PLoS ONE. 2016;11:e0147400.CrossRef
13.
go back to reference Satelli A, Brownlee Z, Mitra A, Meng QH, Li S. Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response. Clin Chem. 2015;61:259–66.CrossRef Satelli A, Brownlee Z, Mitra A, Meng QH, Li S. Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response. Clin Chem. 2015;61:259–66.CrossRef
14.
go back to reference Onstenk W, Kraan J, Mostert B, Timmermans MM, Charehbili A, Smit VTHBM, Kroep JR, Nortier JWR, van de Ven S, Heijns JB, Kessels LW, van Laarhoven HWM, Bos MMEM, van de Velde CJH, Gratama JW, Sieuwerts AM, Martens JWM, Foekens JA, Sleijfer S. Improved circulating tumor cell detection by a combined EpCAM and MCAM Cell Search enrichment approach in patients with breast cancer undergoing neoadjuvant chemotherapy. Mol Cancer Ther. 2015;14:821–7.CrossRef Onstenk W, Kraan J, Mostert B, Timmermans MM, Charehbili A, Smit VTHBM, Kroep JR, Nortier JWR, van de Ven S, Heijns JB, Kessels LW, van Laarhoven HWM, Bos MMEM, van de Velde CJH, Gratama JW, Sieuwerts AM, Martens JWM, Foekens JA, Sleijfer S. Improved circulating tumor cell detection by a combined EpCAM and MCAM Cell Search enrichment approach in patients with breast cancer undergoing neoadjuvant chemotherapy. Mol Cancer Ther. 2015;14:821–7.CrossRef
15.
go back to reference Mostert B, Kraan J, Sieuwerts AM, van der Spoel P, Bolt-de Vries J, Prager-van der Smissen WJC, Smid M, Timmermans AM, Martens JWM, Gratama JW, Foekens JA, Sleijfer S. CD49f-based selection of circulating tumor cells (CTCs) improves detection across breast cancer subtypes. Cancer Lett. 2012;319:49–55.CrossRef Mostert B, Kraan J, Sieuwerts AM, van der Spoel P, Bolt-de Vries J, Prager-van der Smissen WJC, Smid M, Timmermans AM, Martens JWM, Gratama JW, Foekens JA, Sleijfer S. CD49f-based selection of circulating tumor cells (CTCs) improves detection across breast cancer subtypes. Cancer Lett. 2012;319:49–55.CrossRef
16.
go back to reference Horimoto Y, Tokuda E, Murakami F, Uomori T, Himuro T, Nakai K, Orihata G, Iijima K, Togo S, Shimizu H, Saito M. Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study. J Transl Med. 2018;16:287.CrossRef Horimoto Y, Tokuda E, Murakami F, Uomori T, Himuro T, Nakai K, Orihata G, Iijima K, Togo S, Shimizu H, Saito M. Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study. J Transl Med. 2018;16:287.CrossRef
17.
go back to reference Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin. Oncotarget. 2018;9:5545–61.CrossRef Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin. Oncotarget. 2018;9:5545–61.CrossRef
18.
go back to reference Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, Uesugi M, Agoulnik S, Taylor N, Funahashi Y, Matsui J. Eribulin mesylate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states. Br J Cancer. 2014;110:1497–505.CrossRef Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, Uesugi M, Agoulnik S, Taylor N, Funahashi Y, Matsui J. Eribulin mesylate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states. Br J Cancer. 2014;110:1497–505.CrossRef
19.
go back to reference Pierga JY, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, Diéras V, Rolland E, Mignot L, Mathiot C, Bidard FC. High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients. Ann Oncol. 2012;23:618–24.CrossRef Pierga JY, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, Diéras V, Rolland E, Mignot L, Mathiot C, Bidard FC. High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients. Ann Oncol. 2012;23:618–24.CrossRef
20.
go back to reference Helissey C, Berger F, Cottu P, Diéras V, Mignot L, Servois V, Bouleuc C, Asselain B, Pelissier S, Vaucher I, Pierga JY, Bidard FC. Circulating tumor cell thresholds and survival scores in advanced metastatic breast cancer: the observational step of the CirCe01 phase III trial. Cancer Lett. 2015;360:213–8.CrossRef Helissey C, Berger F, Cottu P, Diéras V, Mignot L, Servois V, Bouleuc C, Asselain B, Pelissier S, Vaucher I, Pierga JY, Bidard FC. Circulating tumor cell thresholds and survival scores in advanced metastatic breast cancer: the observational step of the CirCe01 phase III trial. Cancer Lett. 2015;360:213–8.CrossRef
Metadata
Title
Impact of circulating tumour cells on survival of eribulin-treated patients with metastatic breast cancer
Authors
Mayuko Ito
Yoshiya Horimoto
Emi Tokuda
Fumi Murakami
Toshitaka Uomori
Takanori Himuro
Katsuya Nakai
Gotaro Orihata
Kotaro Iijima
Mitsue Saito
Publication date
01-10-2019
Publisher
Springer US
Published in
Medical Oncology / Issue 10/2019
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-019-1314-9

Other articles of this Issue 10/2019

Medical Oncology 10/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.