Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform
Autoři:
Yoon-Sim Yap aff001; Man Chun Leong aff002; Yong Wei Chua aff003; Kiley Wei Jen Loh aff001; Guek Eng Lee aff001; Elaine Hsuen Lim aff001; Rebecca Dent aff001; Raymond Chee Hui Ng aff001; John Heng-Chi Lim aff005; Garima Singh aff002; Angela Tan aff002; Guofeng Guan aff002; Andrew Wu aff002; Yi Fang Lee aff002; Ali Asgar S. Bhagat aff002; Darren Wan-Teck Lim aff001
Působiště autorů:
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
aff001; Biolidics Ltd, Singapore
aff002; Department of Pathology, Singapore General Hospital, Singapore
aff003; Institute of Molecular and Cell Biology, A*Star, Singapore
aff004; Clinical Trials and Epidemiology Office, National Cancer Centre Singapore, Singapore
aff005
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0221305
Souhrn
Objectives
We aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC).
Materials and methods
Peripheral blood samples were collected from 108 BC patients before starting a new line of treatment (“baseline”), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses.
Results
The detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS.
Conclusions
This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.
Klíčová slova:
Blood – Blood counts – Breast cancer – Cancer treatment – Hormones – Metastasis – Prognosis – Microfluidics
Zdroje
1. Tewes M, Aktas B, Welt A, Mueller S, Hauch S, Kimmig R, 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 Research and Treatment. 2008;115(3):581–90. doi: 10.1007/s10549-008-0143-x 18679793
2. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351. doi: 10.1056/NEJMoa040766 15317891
3. Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol. 2005;23. doi: 10.1200/jco.2005.08.140 15735118
4. Giuliano M, Giordano A, Jackson S, De Giorgi U, Mego M, Cohen EN, et al. Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination. Breast Cancer Research. 2014;16(5):440. doi: 10.1186/s13058-014-0440-8 25223629
5. Giordano A, Giuliano M, De Laurentiis M, Arpino G, Jackson S, Handy BC, et al. 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. doi: 10.1093/annonc/mdr434 21965473
6. Wallwiener M, Hartkopf AD, Riethdorf S, Nees J, Sprick MR, Schönfisch B, et al. The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients. BMC Cancer. 2015;15(1):403. doi: 10.1186/s12885-015-1423-6 25972110
7. Kalinsky K, Mayer JA, Xu X, Pham T, Wong KL, Villarin E, et al. Correlation of hormone receptor status between circulating tumor cells, primary tumor, and metastasis in breast cancer patients. Clinical and Translational Oncology. 2015;17(7):539–46. doi: 10.1007/s12094-015-1275-1 25613123
8. Ignatiadis M, Rothe F, Chaboteaux C, Durbecq V, Rouas G, Criscitiello C. HER2-positive circulating tumor cells in breast cancer. PLoS One. 2011;6. doi: 10.1371/journal.pone.0015624 21264346
9. Lv Q, Gong L, Zhang T, Ye J, Chai L, Ni C, et al. Prognostic value of circulating tumor cells in metastatic breast cancer: a systemic review and meta-analysis. Clinical and Translational Oncology. 2016;18(3):322–30. doi: 10.1007/s12094-015-1372-1 26260915
10. Babayan A, Hannemann J, Spötter J, Müller V, Pantel K, Joosse SA. Heterogeneity of Estrogen Receptor Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients. PLOS ONE. 2013;8(9):e75038. doi: 10.1371/journal.pone.0075038 24058649
11. Bidard F-C, de Rycke Y, Asselain B, Dieras V, Lebofsky R, Pierga J-Y. Abstract OT1-1-10: CirCe T-DM1 phase II trial: Assessing the relevance of HER2-amplified circulating tumor cells as a tool to select HER2-negative metastatic breast cancer for treatment with T-DM1. Cancer Research. 2013;73(24 Supplement):OT1-10-OT1-1-. doi: 10.1158/0008-5472.sabcs13-ot1-1-10
12. Bidard F-C, Fehm T, Ignatiadis M, Smerage J, Alix-Panabières C, Janni W, et al. Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials. Cancer Metastasis Reviews. 2013:epub ahead of print-epub ahead of print.
13. Bidard F-C, Romieu G, Jacot W, Cottu P, Dieras V, Lerebours F, et al. Abstract P2-02-17: T-DM1 in HER2-negative metastatic breast cancer patients with HER2-amplified circulating tumor cells: Current status of the CirCe T-DM1 phase II trial. Cancer Research. 2016;76(4 Supplement):P2-02-17-P2-02-17. doi: 10.1158/1538-7445.sabcs15-p2-02-17
14. Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013;339. doi: 10.1126/science.1228522 23372014
15. Thiery Jean P, Lim Chwee T. Tumor Dissemination: An EMT Affair. Cancer Cell. 23(3):272–3. doi: 10.1016/j.ccr.2013.03.004 23518345
16. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, et al. Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases. Clinical Cancer Research. 2004;10(20):6897–904. doi: 10.1158/1078-0432.CCR-04-0378 15501967
17. Karhade M, Hall C, Mishra P, Anderson A, Kuerer H, Bedrosian I, et al. Circulating tumor cells in non-metastatic triple-negative breast cancer. Breast Cancer Research and Treatment. 2014;147(2):325–33. doi: 10.1007/s10549-014-3103-7 25164970
18. Lucci A, Hall CS, Lodhi AK, Bhattacharyya A, Anderson AE, Xiao L, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. The Lancet Oncology. 2012;13(7):688–95. doi: 10.1016/S1470-2045(12)70209-7 22677156
19. Khoo BL, Warkiani ME, Tan DS-W, Bhagat AAS, Irwin D, Lau DP, et al. Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells. PLOS ONE. 2014;9(7):e99409. doi: 10.1371/journal.pone.0099409 24999991
20. Wong VC-L, Ko JM-Y, Lam C-T, Lung ML. Succinct workflows for circulating tumor cells after enrichment: From systematic counting to mutational profiling. PLOS ONE. 2017;12(5):e0177276. doi: 10.1371/journal.pone.0177276 28481895
21. Gabriel MT, Calleja LR, Chalopin A, Ory B, Heymann D. Circulating tumor cells: a review of non–EpCAM-based approaches for cell enrichment and isolation. Clinical chemistry. 2016;62(4):571–81. doi: 10.1373/clinchem.2015.249706 26896446
22. Tan CL, Lim TH, Lim TK, Tan DS-W, Chua YW, Ang MK, et al. Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer. Oncotarget. 2016;7(17):23251. doi: 10.18632/oncotarget.8136 26993609
23. Lee Y, Guan G, Bhagat AA. ClearCell(R) FX, a label-free microfluidics technology for enrichment of viable circulating tumor cells. Cytometry Part A: the journal of the International Society for Analytical Cytology. 2018;93(12):1251–4. Epub 2018/08/07. doi: 10.1002/cyto.a.23507 30080307.
24. Hou HW, Warkiani ME, Khoo BL, Li ZR, Soo RA, Tan DS, et al. Isolation and retrieval of circulating tumor cells using centrifugal forces. Scientific reports. 2013;3:1259. Epub 2013/02/14. doi: 10.1038/srep01259 23405273
25. Sawada T, Araki J, Yamashita T, Masubuchi M, Chiyoda T, Yunokawa M, et al. Prognostic Impact of Circulating Tumor Cell Detected Using a Novel Fluidic Cell Microarray Chip System in Patients with Breast Cancer. EBioMedicine. 2016;11:173–82. doi: 10.1016/j.ebiom.2016.07.027 27495793
26. Adams DL, Adams DK, Stefansson S, Haudenschild C, Martin SS, Charpentier M, et al. Mitosis in circulating tumor cells stratifies highly aggressive breast carcinomas. Breast Cancer Research. 2016;18(1):44. doi: 10.1186/s13058-016-0706-4 27142282
27. Wong NS, Kahn HJ, Zhang L, Oldfield S, Yang L-Y, Marks A, et al. Prognostic significance of circulating tumour cells enumerated after filtration enrichment in early and metastatic breast cancer patients. Breast Cancer Research and Treatment. 2006;99(1):63–9. doi: 10.1007/s10549-006-9181-4 16541316
28. Hammond MEH, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Archives of pathology & laboratory medicine. 2010;134(7):e48–e72.
29. Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. Journal of Clinical Oncology. 2013;31(31):3997–4013. doi: 10.1200/JCO.2013.50.9984 24101045.
30. Pierga JY, Bidard FC, Autret A, Petit T, Andre F, Dalenc F, et al. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab. Annals of Oncology. 2017;28(1):103–9. doi: 10.1093/annonc/mdw535 28177480
31. Bidard FC, Mathiot C, Delaloge S, Brain E, Giachetti S, de Cremoux P, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Annals of Oncology. 2010;21(4):729–33. doi: 10.1093/annonc/mdp391 19850639
32. Mego M, Giordano A, De Giorgi U, Masuda H, Hsu L, Giuliano M, et al. Circulating tumor cells in newly diagnosed inflammatory breast cancer. Breast Cancer Research. 2015;17(1):2. doi: 10.1186/s13058-014-0507-6 25572591
33. Horiguchi J, Takata D, Rokutanda N, Nagaoka R, Tokiniwa H, Tozuka K, et al. Abstract P3-06-29: Change of circulating tumor cells before and after neoadjuvant chemotherapy in patients with primary breast cancer. Cancer Research. 2012;72(24 Supplement):P3-06-29.
34. Liu MC, Shields PG, Warren RD, Cohen P, Wilkinson M, Ottaviano YL. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009;27. doi: 10.1200/jco.2008.20.6664 19752342
35. Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, et al. Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival. Clinical Cancer Research. 2006;12(14):4218.
36. Fraser-Fish J, Ahmad Z, Kumar R, Ebbs B, Fowler G, Flohr P, et al. Molecular characterization of PDL1 status of circulating tumor cells (CTCs) isolated with a novel label-free inertial microfluidic system from patients (pts) with advanced cancers. Annals of Oncology. 2016;27(suppl_6):76P–P. doi: 10.1093/annonc/mdw363.24
37. Giuliano M, Giordano A, Jackson S, Hess KR, De Giorgi U, Mego M, et al. Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res. 2011;13. doi: 10.1186/bcr2907 21699723
38. Peeters DJ, van Dam PJ, Van den Eynden GG, Rutten A, Wuyts H, Pouillon L, et al. Detection and prognostic significance of circulating tumour cells in patients with metastatic breast cancer according to immunohistochemical subtypes. British journal of cancer. 2014;110(2):375–83. Epub 2013/12/25. doi: 10.1038/bjc.2013.743 24366294
39. Paoletti C, Larios JM, Muñiz MC, Aung K, Cannell EM, Darga EP, et al. Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance. Molecular oncology. 2016;10(7):1078–85. doi: 10.1016/j.molonc.2016.04.006 27178224
40. Paolillo C, Mu Z, Rossi G, Schiewer MJ, Nguyen T, Austin L, et al. Detection of Activating Estrogen Receptor Gene (ESR1) Mutations in Single Circulating Tumor Cells. Clinical Cancer Research. 2017. doi: 10.1158/1078-0432.ccr-17-1173 28679775
41. Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN, et al. Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther. 2012;11. doi: 10.1158/1535-7163.mct-12-0460 22973057
Článek vyšel v časopise
PLOS One
2019 Číslo 9
- Tisícileté topoly, mokří psi, stárnoucí kočky a ospalé octomilky – „jednohubky“ z výzkumu 2024/41
- Jaké jsou aktuální trendy v léčbě karcinomu slinivky?
- Může hubnutí souviset s vyšším rizikem nádorových onemocnění?
- Menstruační krev má značný diagnostický potenciál, mimo jiné u diabetu
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
Nejčtenější v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy