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Published in: Breast Cancer Research and Treatment 3/2009

01-02-2009 | Clinical Trial

HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer

Authors: Julie E. Lang, Kailash Mosalpuria, Massimo Cristofanilli, Savitri Krishnamurthy, James Reuben, Balraj Singh, Isabelle Bedrosian, Funda Meric-Bernstam, Anthony Lucci

Published in: Breast Cancer Research and Treatment | Issue 3/2009

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Abstract

Introduction Circulating tumor cells (CTCs) correlate with worse prognosis in patients with metastatic breast cancer, but there are little data on CTCs in operable patients. We hypothesized that primary tumor characteristics would predict the likelihood of identifying CTCs in patients with operable breast cancer. Methods Clinical and pathological data from 92 patients with operable breast cancer were collected. The CellSearch system was used to detect CTCs in 30 ml of peripheral blood. CTCs were defined as nucleated cells lacking CD45 but expressing cytokeratins 8, 18, or 19. Univariate analysis was performed to determine if the presence of any primary tumor characteristic was predictive of CTCs. As a secondary objective we evaluated if nodal or bone marrow status was predictive of CTCs. Results Thirty-eight percent of patients (35/92) had evidence of CTCs, with a median number of 1.0 CTC per CTC positive patient (range 1–22). HER2 status was the sole primary tumor characteristic that reliably predicted the presence of CTCs (P = 0.01, risk ratio = 3.66). No significant association was found between the presence of CTCs and tumor size (T), estrogen receptor (ER) status, progesterone receptor (PR) status, grade, histologic type, degree of nodal involvement (N), lymphovascular invasion (LVI) or Ki-67 proliferation. Bone marrow micrometastases were found in 17/64 (26.6%) of the patients but did not correlate with the presence of CTCs. Conclusion HER2 status was the only primary tumor characteristic that correlated with the presence of CTCs. Long-term follow-up will be required to determine the significance of CTCs in operable breast cancer.
Literature
1.
go back to reference Braun S, Vogl FD, Naume B et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802PubMedCrossRef Braun S, Vogl FD, Naume B et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802PubMedCrossRef
2.
go back to reference Lang JE, Hall CS, Singh B et al (2007) Significance of micrometastasis in bone marrow and blood of operable breast cancer patients: research tool or clinical application? Expert Rev Anticancer Ther 7:1463–1472PubMedCrossRef Lang JE, Hall CS, Singh B et al (2007) Significance of micrometastasis in bone marrow and blood of operable breast cancer patients: research tool or clinical application? Expert Rev Anticancer Ther 7:1463–1472PubMedCrossRef
3.
go back to reference Wulfing P, Borchard J, Buerger H et al (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12:1715–1720PubMedCrossRef Wulfing P, Borchard J, Buerger H et al (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12:1715–1720PubMedCrossRef
4.
go back to reference Pierga JY, Bonneton C, Vincent-Salomon A et al (2004) Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clinical Cancer Research 10:1392–1400PubMedCrossRef Pierga JY, Bonneton C, Vincent-Salomon A et al (2004) Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clinical Cancer Research 10:1392–1400PubMedCrossRef
5.
go back to reference Meng S, Tripathy D, Shete S et al (2004) HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA 101:9393–9398PubMedCrossRef Meng S, Tripathy D, Shete S et al (2004) HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA 101:9393–9398PubMedCrossRef
6.
go back to reference Xenidis N, Perraki M, Kafousi M et al (2006) Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin Oncol 24:3756–3762PubMedCrossRef Xenidis N, Perraki M, Kafousi M et al (2006) Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin Oncol 24:3756–3762PubMedCrossRef
7.
go back to reference Zach O, Kasparu H, Wagner H et al (2002) Prognostic value of tumour cell detection in peripheral blood of breast cancer patients. Acta Med Austriaca Suppl 59:32–34PubMed Zach O, Kasparu H, Wagner H et al (2002) Prognostic value of tumour cell detection in peripheral blood of breast cancer patients. Acta Med Austriaca Suppl 59:32–34PubMed
8.
go back to reference Gaforio JJ, Serrano MJ, Sanchez-Rovira P et al (2003) Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis. Int J Cancer 107:984–990PubMedCrossRef Gaforio JJ, Serrano MJ, Sanchez-Rovira P et al (2003) Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis. Int J Cancer 107:984–990PubMedCrossRef
9.
go back to reference Stathopoulos EN, Sanidas E, Kafousi M et al (2005) Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes. Ann Oncol 16:240–246PubMedCrossRef Stathopoulos EN, Sanidas E, Kafousi M et al (2005) Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes. Ann Oncol 16:240–246PubMedCrossRef
10.
go back to reference Benoy IH, Elst H, Philips M et al (2006) Real-time RT-PCR detection of disseminated tumour cells in bone marrow has superior prognostic significance in comparison with circulating tumour cells in patients with breast cancer. Br J Cancer 94:672–680PubMed Benoy IH, Elst H, Philips M et al (2006) Real-time RT-PCR detection of disseminated tumour cells in bone marrow has superior prognostic significance in comparison with circulating tumour cells in patients with breast cancer. Br J Cancer 94:672–680PubMed
11.
go back to reference Naume B, Borgen E, Beiske K et al (1997) Immunomagnetic techniques for the enrichment and detection of isolated breast carcinoma cells in bone marrow and peripheral blood. J Hematother 6:103–114PubMed Naume B, Borgen E, Beiske K et al (1997) Immunomagnetic techniques for the enrichment and detection of isolated breast carcinoma cells in bone marrow and peripheral blood. J Hematother 6:103–114PubMed
12.
go back to reference Racila E, Euhus D, Weiss AJ et al (1998) Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci U S A 95:4589–4594PubMedCrossRef Racila E, Euhus D, Weiss AJ et al (1998) Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci U S A 95:4589–4594PubMedCrossRef
13.
go back to reference Zhou L, Wang K, Tan W et al (2006) Quantitative intracellular molecular profiling using a one-dimensional flow system. Analytical chemistry 78:6246–6251PubMedCrossRef Zhou L, Wang K, Tan W et al (2006) Quantitative intracellular molecular profiling using a one-dimensional flow system. Analytical chemistry 78:6246–6251PubMedCrossRef
14.
go back to reference Ring A, Smith IE, Dowsett M (2004) Circulating tumour cells in breast cancer. Lancet Oncol 5:79–88PubMedCrossRef Ring A, Smith IE, Dowsett M (2004) Circulating tumour cells in breast cancer. Lancet Oncol 5:79–88PubMedCrossRef
15.
go back to reference Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791PubMedCrossRef Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791PubMedCrossRef
16.
go back to reference Tibbe AG, Miller MC, Terstappen LW (2007) Statistical considerations for enumeration of circulating tumor cells. Cytometry A 71:154–162PubMed Tibbe AG, Miller MC, Terstappen LW (2007) Statistical considerations for enumeration of circulating tumor cells. Cytometry A 71:154–162PubMed
17.
go back to reference Allard WJ, Matera J, Miller MC et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904PubMedCrossRef Allard WJ, Matera J, Miller MC et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904PubMedCrossRef
18.
go back to reference Riethdorf S, Fritsche H, Muller V et al (2007) Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res 13:920–928PubMedCrossRef Riethdorf S, Fritsche H, Muller V et al (2007) Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res 13:920–928PubMedCrossRef
19.
go back to reference Rack B, Schindlbeck C, Janni W et al (2006) Incidence of circulating tumor cells (CTCs) in peripheral blood of breast cancer patients at primary diagnosis—a potential tool for risk stratification, ASCO Annual Meeting (J Clin Oncol (ed) (2006) 2006 ASCO Annual Meeting Proceedings Part I 24(18S: June 20 Supplement):20053) Rack B, Schindlbeck C, Janni W et al (2006) Incidence of circulating tumor cells (CTCs) in peripheral blood of breast cancer patients at primary diagnosis—a potential tool for risk stratification, ASCO Annual Meeting (J Clin Oncol (ed) (2006) 2006 ASCO Annual Meeting Proceedings Part I 24(18S: June 20 Supplement):20053)
20.
go back to reference Rack B, Schindlbeck C, Hofmann S et al (2007) Circulating tumor cells (CTCs) in peripheral blood of primary breast cancer patients, ASCO Annual Meeting. J Clin Oncol (2007) 2007 ASCO Annual Meeting Proceedings Part I 25(18S: June 20 Supplement):10595 Rack B, Schindlbeck C, Hofmann S et al (2007) Circulating tumor cells (CTCs) in peripheral blood of primary breast cancer patients, ASCO Annual Meeting. J Clin Oncol (2007) 2007 ASCO Annual Meeting Proceedings Part I 25(18S: June 20 Supplement):10595
21.
go back to reference Nimeus-Malmstrom E, Ritz C, Eden P et al (2006) Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy. Eur J Cancer 42:2729–2737PubMedCrossRef Nimeus-Malmstrom E, Ritz C, Eden P et al (2006) Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy. Eur J Cancer 42:2729–2737PubMedCrossRef
22.
go back to reference Pantel K, Schlimok G, Braun S et al (1993) Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J Natl Cancer Inst 85:1419–1424PubMedCrossRef Pantel K, Schlimok G, Braun S et al (1993) Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J Natl Cancer Inst 85:1419–1424PubMedCrossRef
23.
go back to reference Smith I, Procter M, D Gelber R et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369:29–36PubMedCrossRef Smith I, Procter M, D Gelber R et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369:29–36PubMedCrossRef
24.
go back to reference Alvarado M, Brissaud C, Scott J et al (2007) Disseminated tumor cells correlate with estrogen receptor positivity in operable breast cancer patients. San Antonio Breast Cancer Symposium Alvarado M, Brissaud C, Scott J et al (2007) Disseminated tumor cells correlate with estrogen receptor positivity in operable breast cancer patients. San Antonio Breast Cancer Symposium
25.
go back to reference Meng S, Tripathy D, Shete S et al (2006) uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci USA 103:17361–17365PubMedCrossRef Meng S, Tripathy D, Shete S et al (2006) uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci USA 103:17361–17365PubMedCrossRef
26.
go back to reference Ignatiadis M, Xenidis N, Perraki M et al (2007) Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer. J Clin Oncol 25:5194–5202PubMedCrossRef Ignatiadis M, Xenidis N, Perraki M et al (2007) Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer. J Clin Oncol 25:5194–5202PubMedCrossRef
27.
go back to reference Hayes DF, Walker TM, Singh B et al (2002) Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int J Oncol 21:1111–1117PubMed Hayes DF, Walker TM, Singh B et al (2002) Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int J Oncol 21:1111–1117PubMed
28.
go back to reference McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 97:1180–1184PubMedCrossRef McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 97:1180–1184PubMedCrossRef
29.
go back to reference Cristofanilli M, Broglio KR, Guarneri V et al (2007) Circulating tumor cells in metastatic breast cancer: biologic staging beyond tumor burden. Clin Breast Cancer 7:471–479PubMedCrossRef Cristofanilli M, Broglio KR, Guarneri V et al (2007) Circulating tumor cells in metastatic breast cancer: biologic staging beyond tumor burden. Clin Breast Cancer 7:471–479PubMedCrossRef
Metadata
Title
HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer
Authors
Julie E. Lang
Kailash Mosalpuria
Massimo Cristofanilli
Savitri Krishnamurthy
James Reuben
Balraj Singh
Isabelle Bedrosian
Funda Meric-Bernstam
Anthony Lucci
Publication date
01-02-2009
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-008-9951-2

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