Circulating tumor cells before and during follow-up after breast cancer surgery

van Dalum,Guus; van der Stam,Gert  Jan; Tibbe,Arjan G.J.; Franken,Bas; Mastboom,Walter  J.B.; Vermes,Ivan; de Groot,Marco  R.; Terstappen,Leon  W.M.M.

doi:10.3892/ijo.2014.2694

Circulating tumor cells before and during follow-up after breast cancer surgery

Authors:
- Guus van Dalum
- Gert Jan van der Stam
- Arjan G.J. Tibbe
- Bas Franken
- Walter J.B. Mastboom
- Ivan Vermes
- Marco R. de Groot
- Leon W.M.M. Terstappen
View Affiliations

Affiliations: Medical Cell BioPhysics Group, MIRA Institute, University of Twente, Enschede, The Netherlands, Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands, Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands
Published online on: October 6, 2014 https://doi.org/10.3892/ijo.2014.2694
Pages: 407-413

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free and overall survival for patients with metastatic and newly diagnosed breast cancer. The present study was undertaken to explore whether the presence of CTC before and during follow-up after surgery is associated with recurrence free survival (RFS) and overall survival (OS). In a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 403 stage I-III patients before undergoing surgery for breast cancer (A) and if available 1 week after surgery (B), after adjuvant chemo- and/or radiotherapy or before start of long-term hormonal therapy (C), one (D), two (E) and three (F) years after surgery. Patients were stratified into unfavorable (CTC ≥1) and favorable (CTC=0) prognostic groups. >1 CTC in 30 ml blood was detected in 75/403 (19%) at A, 66/367 (18%) at B, 40/263 (15%) at C, 30/235 (12%) at D, 18/144 (11%) at E and 11/83 (13%) at F. RFS and OS was significantly lower for unfavorable CTC as compared to favorable CTC before surgery (p=0.022 and p=0.006), after adjuvant therapy (p<0.001 and p=0.018) and one (p=0.006 and p=0.013) and two (p<0.001 and p=0.045) years after surgery, but not 1 week post-surgery. The presence of CTC in blood drawn pre and one and two years after surgery, but not post-surgery is associated with shorter RFS and OS for stage I-III breast cancer.

View Figures

View References

1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2	Boyages J, Chua B, Taylor R, Bilous M, Salisbury E, Wilcken N and Ung O: Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy. Br J Surg. 89:789–796. 2002. View Article : Google Scholar : PubMed/NCBI
3	Colomer R, Viñas G, Beltran M, et al: Validation of the 2001 St Gallen risk categories for node-negative breast cancer using a database from the Spanish Breast Cancer Research Group (GEICAM). J Clin Oncol. 22:961–962. 2004. View Article : Google Scholar : PubMed/NCBI
4	Lundin J, Lehtimäki T, Lundin M, et al: Generalisability of survival estimates for patients with breast cancer--a comparison across two population-based series. Eur J Cancer. 42:3228–3235. 2006. View Article : Google Scholar : PubMed/NCBI
5	Olivotto IA, Bajdik CD, Ravdin PM, et al: Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol. 23:2716–2725. 2005. View Article : Google Scholar : PubMed/NCBI
6	Cronin M, Pho M, Dutta D, et al: Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. Am J Pathol. 164:35–42. 2004. View Article : Google Scholar
7	Sørlie T, Perou CM, Tibshirani R, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 98:10869–10874. 2001.PubMed/NCBI
8	Perou CM, Sørlie T, Eisen MB, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI
9	Wang Y, Klijn JGM, Zhang Y, et al: Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 365:671–679. 2005. View Article : Google Scholar : PubMed/NCBI
10	West M, Blanchette C, Dressman H, et al: Predicting the clinical status of human breast cancer by using gene expression profiles. Proc Natl Acad Sci USA. 98:11462–11467. 2001. View Article : Google Scholar : PubMed/NCBI
11	Van ‘t Veer LJ, Dai H, van de Vijver MJ, et al: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 415:530–536. 2002.PubMed/NCBI
12	Meng S, Tripathy D, Frenkel EP, et al: Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 10:8152–8162. 2004. View Article : Google Scholar : PubMed/NCBI
13	Vessella RL, Pantel K and Mohla S: Tumor cell dormancy: an NCI workshop report. Cancer Biol Ther. 6:1496–1504. 2007. View Article : Google Scholar : PubMed/NCBI
14	Fehm T, Braun S, Muller V, et al: A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer. 107:885–892. 2006. View Article : Google Scholar : PubMed/NCBI
15	Braun S and Marth C: Circulating tumor cells in metastatic breast cancer - toward individualized treatment? N Engl J Med. 351:824–826. 2004. View Article : Google Scholar : PubMed/NCBI
16	Braun S, Vogl F and Naume B: A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 353:793–802. 2005. View Article : Google Scholar : PubMed/NCBI
17	Allard WJ, Matera J, Miller MC, et al: Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 10:6897–6904. 2004. View Article : Google Scholar : PubMed/NCBI
18	Cristofanilli M and Budd G: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Engl J Med. 351:781–791. 2004. View Article : Google Scholar : PubMed/NCBI
19	Liu MC, Shields PG, Warren RD, et al: Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 27:5153–5159. 2009. View Article : Google Scholar : PubMed/NCBI
20	Pierga JY, Hajage D, Bachelot T, et al: 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. 23:618–624. 2012. View Article : Google Scholar
21	Bidard F, Peeters D and Fehm T: Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 15:406–414. 2014. View Article : Google Scholar : PubMed/NCBI
22	Franken B, de Groot MR, Mastboom WJB, Vermes I, van der Palen J, Tibbe AGJ and Terstappen LWMM: Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res. 14:R1332012. View Article : Google Scholar : PubMed/NCBI
23	Mathiot C, Brain E, Delaloge S, Pierga J, Marty M, Giachetti S and de Cremoux P: 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. 14:7004–7010. 2008. View Article : Google Scholar
24	Jueckstock JK, Rack BK, Zwingers T, Hepp PGM, Schneeweiss A, Beckmann MW, Lichtenegger W, Sommer HL, Pantel K, Tesch H, Forstbauer H, Lorenz R, Rezai M, Neugebauer JK, Andergassen U, Friese K, et al: Prognostic relevance of circulating tumor cells (CTC) before adjuvant chemotherapy in patients with breast cancer: results of the German SUCCESS trial. J Clin Oncol. 29(Suppl): 10332011.
25	Lucci A, Hall CS, Lodhi AK, et al: Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. 13:688–695. 2012. View Article : Google Scholar : PubMed/NCBI
26	Janni WJ, Rack BK, Terstappen LWMM, et al: A pooled analysis of the prognostic relevance of circulating tumor cells in early breast cancer. Cancer Res. 73(Suppl 24): PD6–6. 2013. View Article : Google Scholar
27	Bidard FC, Mathiot C, Delaloge S, et al: Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol. 21:729–733. 2010. View Article : Google Scholar : PubMed/NCBI
28	National guidelines breast cancer (richlijn mamacarcinoom 2008). http://www.cbo.nl.
29	R Core Team. R: A Language and Environment for Statistical Computing. Version 3.0.1 (2013-05-16).
30	Coumans FAW, Ligthart ST, Uhr JW and Terstappen LWMM: Challenges in the enumeration and phenotyping of CTC. Clin Cancer Res. 18:5711–5718. 2012. View Article : Google Scholar : PubMed/NCBI
31	Coumans FAW, Ligthart ST and Terstappen LWMM: Interpretation of changes in circulating tumor cell counts. Transl Oncol. 5:486–491. 2012. View Article : Google Scholar : PubMed/NCBI
32	Barradas AM and Terstappen LWMM: Towards the biological understanding of CTC: capture technologies, definitions and potential to create metastasis. Cancers (Basel). 5:1619–1642. 2013. View Article : Google Scholar : PubMed/NCBI
33	Fischer JC, Niederacher D, Topp SA, et al: Diagnostic leuka-pheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients. Proc Natl Acad Sci USA. 110:16580–16585. 2013. View Article : Google Scholar : PubMed/NCBI
34	Coumans FAW, Siesling S and Terstappen LWMM: Detection of cancer before distant metastasis. BMC Cancer. 13:2832013. View Article : Google Scholar : PubMed/NCBI
35	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. 14:70042008. View Article : Google Scholar
36	Van Dalum G, de Groot M, Stam GJ, et al: Importance of circulating tumor cells in newly diagnosed colorectal cancer. In: Proc 105th Annual Meeting Amer Assoc for Cancer Res; San Diego, CA. abst 3064. 2014, PubMed/NCBI
37	Ligthart ST, Coumans FAW, Attard G, Cassidy AM, de Bono JS and Terstappen LWMM: Unbiased and automated identification of a circulating tumour cell definition that associates with overall survival. PLoS One. 6:e274192011. View Article : Google Scholar : PubMed/NCBI
38	Swennenhuis JF, Tibbe AGJ, Levink R, Sipkema RCJ and Terstappen LWMM: Characterization of circulating tumor cells by fluorescence in situ hybridization. Cytometry A. 75:520–527. 2009. View Article : Google Scholar : PubMed/NCBI
39	Swennenhuis JF, Reumers J, Thys K, Aerssens J and Terstappen LWMM: Efficiency of whole genome amplification of single circulating tumor cells enriched by CellSearch and sorted by FACS. Genome Med. 5:1062013. View Article : Google Scholar : PubMed/NCBI
40	Klein CA, Blankenstein TJF, Schmidt-Kittler O, Petronio M, Polzer B and Stoecklein NH: Mechanisms of disease Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet. 360:683–689. 2002. View Article : Google Scholar : PubMed/NCBI
41	Meng S, Tripathy D, Shete S, et al: uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci USA. 103:17361–17365. 2006. View Article : Google Scholar : PubMed/NCBI
42	Fehm T, Sagalowsky A, Clifford E, et al: Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res. 8:2073–2084. 2002.
43	Meng S, Tripathy D, Shete S, et al: HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA. 101:9393–9398. 2004. View Article : Google Scholar : PubMed/NCBI
44	Uhr JW and Pantel K: Controversies in clinical cancer dormancy. Proc Natl Acad Sci USA. 108:12396–12400. 2011. View Article : Google Scholar : PubMed/NCBI
45	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. 101:61–66. 2009. View Article : Google Scholar : PubMed/NCBI
46	Mostert B, Kraan J, Sieuwerts AM, et al: CD49f-based selection of circulating tumor cells (CTCs) improves detection across breast cancer subtypes. Cancer Lett. 319:49–55. 2012. View Article : Google Scholar : PubMed/NCBI
47	Coumans FAW, van Dalum G, Beck M and Terstappen LWMM: Filter characteristics influencing circulating tumor cell enrichment from whole blood. PLoS One. 8:e617702013. View Article : Google Scholar : PubMed/NCBI
48	Hou HW, Warkiani ME, Khoo BL, et al: Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep. 3:12592013.PubMed/NCBI
49	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 circulatingtumor cells. Am J Pathol. 156:57–63. 2000. View Article : Google Scholar : PubMed/NCBI