Skip to main content
Top
Published in: Annals of Surgical Oncology 5/2017

01-05-2017 | Breast Oncology

Usefulness of CTC and DTC-BM Detection for Adjuvant Therapy Effects and Prognosis Prediction in Early Breast Carcinoma: Results of 8–11 Years of Follow-up Evaluation

Authors: Hiroshi Takeyama, MD, T. Shimada, MD, S. Kinoshita, MD, K. Uchida, MD

Published in: Annals of Surgical Oncology | Issue 5/2017

Login to get access

Abstract

Background

Circulating tumor cells (CTCs) reportedly have been detected in the peripheral blood of more than 50% of breast carcinoma cases with distant metastases. Moreover, the survival period is shorter for patients who had more than five CTCs after a single chemotherapy treatment. However, a few data show the relationships between CTCs and expressions of disseminated tumor cells in the bone marrow (DTCs-BM), including treatment effects and prognoses in early breast carcinomas.

Methods

In this study, CTCs and DTC-BMs were measured by the CellSearch System for 20 patients with stages 1–3 carcinomas, who were followed for 8–11 years.

Results

CTCs in 2 (10%) of 20 breast carcinomas, more than 1 CTC was detected before adjuvant therapy, and both cases showed a decrease to 0 after chemotherapy. DTC-BMs in 19 (95%) of the 20 primary cases, more than 1 cell was found in the BM. After adjuvant therapy, 16 cases showed a decrease to 0–10 cells, 2 cases to 11–20 cells, and 2 cases to more than 21 cells. Six patients experienced recurrence. One of the two CTC-positive cases (>21 cells) had bone and liver metastasis within 11 months. Among the DTC-BM cases, only 1 (16.7%) of the 6 primary patients with 11–20 cells had recurrence, whereas 4 (80%) of the 5 patients with more than 21 cells had recurrence 3–6 years later.

Conclusions

Detection of DTC-BMs is useful for observing adjuvant therapy effects and for predicting relatively late-phase metastasis. The cluster status of CTCs suggests early relapsing.
Literature
1.
go back to reference Tsukuma H, Ajiki W, Ioka A, Oshima A. Survival of cancer patients diagnosed between 1993 and 1996: a collaborative study of population-based cancer registries in Japan. Research Group of Population-Based Cancer Registries of Japan. Jpn J Clin Oncol. 2006;36:602–7.CrossRefPubMed Tsukuma H, Ajiki W, Ioka A, Oshima A. Survival of cancer patients diagnosed between 1993 and 1996: a collaborative study of population-based cancer registries in Japan. Research Group of Population-Based Cancer Registries of Japan. Jpn J Clin Oncol. 2006;36:602–7.CrossRefPubMed
2.
go back to reference Woodward WA, Vinh-Hung V, Ueno NT, Cheng YC, Royce M, Tai P. Prognostic value of nodal ratios in node-positive breast cancer. J Clin Oncol. 2003;24:2910–16.CrossRef Woodward WA, Vinh-Hung V, Ueno NT, Cheng YC, Royce M, Tai P. Prognostic value of nodal ratios in node-positive breast cancer. J Clin Oncol. 2003;24:2910–16.CrossRef
3.
go back to reference Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;25(353):793–802.CrossRef Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;25(353):793–802.CrossRef
4.
go back to reference 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;351:781–91.CrossRefPubMed 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;351:781–91.CrossRefPubMed
5.
go back to reference Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC. 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. 2006;12:4218–24.CrossRefPubMed Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC. 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. 2006;12:4218–24.CrossRefPubMed
6.
go back to reference Daskalaki A, Agelaki S, Perraki M, Apostolaki S, Xenidis N, Stathopoulos E, et al. Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer. Br J Cancer 2009;101:589–97.CrossRefPubMedPubMedCentral Daskalaki A, Agelaki S, Perraki M, Apostolaki S, Xenidis N, Stathopoulos E, et al. Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer. Br J Cancer 2009;101:589–97.CrossRefPubMedPubMedCentral
7.
go back to reference Meads MB, Hazlehurst LA, Dalton WS. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res. 2008;14:2519–26.CrossRefPubMed Meads MB, Hazlehurst LA, Dalton WS. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res. 2008;14:2519–26.CrossRefPubMed
8.
go back to reference Bidard FC, Vincent-Salomon A, Sigal-Zafrani B, Dieras V, Mathiot C, Mignot L, et al. Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Ann Oncol. 2008;19:496–500.CrossRefPubMed Bidard FC, Vincent-Salomon A, Sigal-Zafrani B, Dieras V, Mathiot C, Mignot L, et al. Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Ann Oncol. 2008;19:496–500.CrossRefPubMed
9.
go back to reference Krishnamurthy S, Cristofanilli M, Singh B, Reuben J, Gao H, Cohen EN, et al. Detection of minimal residual disease in blood and bone marrow in early-stage breast cancer. Cancer 2010;116:3330–7.CrossRefPubMed Krishnamurthy S, Cristofanilli M, Singh B, Reuben J, Gao H, Cohen EN, et al. Detection of minimal residual disease in blood and bone marrow in early-stage breast cancer. Cancer 2010;116:3330–7.CrossRefPubMed
10.
go back to reference Schindlbeck C, Kampik T, Janni W, Rack B, Jeschke U, Krajewski S, et al. Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas. Breast Cancer Res. 2005;7:R1174–85.CrossRefPubMedPubMedCentral Schindlbeck C, Kampik T, Janni W, Rack B, Jeschke U, Krajewski S, et al. Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas. Breast Cancer Res. 2005;7:R1174–85.CrossRefPubMedPubMedCentral
11.
go back to reference Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.CrossRef Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.CrossRef
12.
go back to reference van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224–37.CrossRefPubMed van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224–37.CrossRefPubMed
13.
go back to reference Muller V, Stahmann N, Riethdorf S, Rau T, Zabel T, Goetz A, et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res. 2005;11:3678–85.CrossRefPubMed Muller V, Stahmann N, Riethdorf S, Rau T, Zabel T, Goetz A, et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res. 2005;11:3678–85.CrossRefPubMed
14.
go back to reference Zabaglo L, Ormerod MG, Parton M, Ring A, Smith IE, Dowsett M. Cell filtration-laser scanning cytometry for the characterisation of circulating breast cancer cells. Cytometry A 2003;55:102–8.CrossRefPubMed Zabaglo L, Ormerod MG, Parton M, Ring A, Smith IE, Dowsett M. Cell filtration-laser scanning cytometry for the characterisation of circulating breast cancer cells. Cytometry A 2003;55:102–8.CrossRefPubMed
15.
go back to reference Nora Dickson M, Tsinberg P, Tang Z, Bischoff FZ, Wilson T, Leonard EF. Efficient capture of circulating tumor cells with a novel immunocytochemical microfluidic device. Biomicrofluidics 2011;5(3):34119–915.CrossRefPubMed Nora Dickson M, Tsinberg P, Tang Z, Bischoff FZ, Wilson T, Leonard EF. Efficient capture of circulating tumor cells with a novel immunocytochemical microfluidic device. Biomicrofluidics 2011;5(3):34119–915.CrossRefPubMed
16.
go back to reference Schindlbeck C, Pfab G, Jueckstock J, Andergassen U, Sommer H, Janni W, et al. Prognostic relevance of disseminated tumor cells in the bone marrow of patients with primary breast cancer: results of a standardized follow-up. Anticancer Res. 2011;31:2749–55.PubMed Schindlbeck C, Pfab G, Jueckstock J, Andergassen U, Sommer H, Janni W, et al. Prognostic relevance of disseminated tumor cells in the bone marrow of patients with primary breast cancer: results of a standardized follow-up. Anticancer Res. 2011;31:2749–55.PubMed
17.
go back to reference Weihrauch MR, Skibowski E, Draube A, Geller A, Tesch H, Diehl V, et al. Immunomagnetic enrichment and detection of isolated tumor cells in bone marrow of patients with epithelial malignancies. Clin Exp Metastasis 2002,19:617–21.CrossRefPubMed Weihrauch MR, Skibowski E, Draube A, Geller A, Tesch H, Diehl V, et al. Immunomagnetic enrichment and detection of isolated tumor cells in bone marrow of patients with epithelial malignancies. Clin Exp Metastasis 2002,19:617–21.CrossRefPubMed
18.
go back to reference Banys M, Müller V, Melcher C, Aktas B, Kasimir-Bauer S, Hagenbeck C, et al. Circulating tumor cells in breast cancer. Clin Chim Acta 2013;23(423):39–45.CrossRef Banys M, Müller V, Melcher C, Aktas B, Kasimir-Bauer S, Hagenbeck C, et al. Circulating tumor cells in breast cancer. Clin Chim Acta 2013;23(423):39–45.CrossRef
19.
go back to reference Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, 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. 2011;17:2967–76.CrossRefPubMed Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, 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. 2011;17:2967–76.CrossRefPubMed
20.
go back to reference Janni W, Gastroph S, Hepp F, Kentenich C, Rjosk D, Schindlbeck C, et al. Prognostic significance of an increased number of micrometastatic tumor cells in the bone marrow of patients with first recurrence of breast carcinoma. Cancer 2000;88:2252–9.CrossRefPubMed Janni W, Gastroph S, Hepp F, Kentenich C, Rjosk D, Schindlbeck C, et al. Prognostic significance of an increased number of micrometastatic tumor cells in the bone marrow of patients with first recurrence of breast carcinoma. Cancer 2000;88:2252–9.CrossRefPubMed
21.
go back to reference Pachmann K, Camara O, Kavallaris A, Krauspe S, Malarski N, Gajda M, 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. 2008;26:1208–15.CrossRefPubMed Pachmann K, Camara O, Kavallaris A, Krauspe S, Malarski N, Gajda M, 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. 2008;26:1208–15.CrossRefPubMed
22.
go back to reference Benoy IH, Elst H, Philips M, Wuyts H, Van Dam P, Scharpe S, et al. Prognostic significance of disseminated tumor cells as detected by quantitative real-time reverse-transcriptase polymerase chain reaction in patients with breast cancer. Clin Breast Cancer 2006;7:146–52.CrossRefPubMed Benoy IH, Elst H, Philips M, Wuyts H, Van Dam P, Scharpe S, et al. Prognostic significance of disseminated tumor cells as detected by quantitative real-time reverse-transcriptase polymerase chain reaction in patients with breast cancer. Clin Breast Cancer 2006;7:146–52.CrossRefPubMed
23.
go back to reference Molloy TJ, Bosma AJ, Baumbusch LO, Synnestvedt M, Borgen E, Russnes HG, et al. The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res. 2011;13(3):R61.1–11. Molloy TJ, Bosma AJ, Baumbusch LO, Synnestvedt M, Borgen E, Russnes HG, et al. The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res. 2011;13(3):R61.1–11.
24.
go back to reference Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 2014;28(158):1110–22.CrossRef Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 2014;28(158):1110–22.CrossRef
26.
go back to reference Peeters DJ, Van den Eynden GG, van Dam PJ, Prove A, Benoy IH, van Dam PA, et al. Circulating tumour cells in the central and the peripheral venous compartment in patients with metastatic breast cancer. Br J Cancer 2011;104:1472–7.CrossRefPubMedPubMedCentral Peeters DJ, Van den Eynden GG, van Dam PJ, Prove A, Benoy IH, van Dam PA, et al. Circulating tumour cells in the central and the peripheral venous compartment in patients with metastatic breast cancer. Br J Cancer 2011;104:1472–7.CrossRefPubMedPubMedCentral
27.
go back to reference Schindlbeck C, Andergassen U, Hofmann S, Jückstock J, Jeschke U, Sommer H, et al. Comparison of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients. J Cancer Res Clin Oncol. 2013;139:1055–62. doi:10.1007/s00432-013-1418-0 (Epub 23 March 2013).CrossRefPubMed Schindlbeck C, Andergassen U, Hofmann S, Jückstock J, Jeschke U, Sommer H, et al. Comparison of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients. J Cancer Res Clin Oncol. 2013;139:1055–62. doi:10.​1007/​s00432-013-1418-0 (Epub 23 March 2013).CrossRefPubMed
Metadata
Title
Usefulness of CTC and DTC-BM Detection for Adjuvant Therapy Effects and Prognosis Prediction in Early Breast Carcinoma: Results of 8–11 Years of Follow-up Evaluation
Authors
Hiroshi Takeyama, MD
T. Shimada, MD
S. Kinoshita, MD
K. Uchida, MD
Publication date
01-05-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 5/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5714-1

Other articles of this Issue 5/2017

Annals of Surgical Oncology 5/2017 Go to the issue