Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes

Taku Nakagawa, Steve R. Martinez, Yasufumi Goto, Kazuo Koyanagi, Minoru Kitago, Tatsushi Shingai, David A. Elashoff, Xing Ye, Frederick R. Singer, Armando E. Giuliano, Dave S B Hoon

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Abstract

Purpose: Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status. Experimental Design: Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normalhealthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status. Results: CTCs were detected in 39 of 90 (43%) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29%) stage I patients, 19 of 42 (45%) stage II patients, and 10 of 13 (77%) stage III patients. In multivariate analysis, only lymphovascular invasion and ≥2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95% confidence interval (95% CI), 3.52-43.77, P < 0.0001; and OR, 3.88; 95% CI, 1.69-8.89, P = 0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P = 0.0004). At least one CTC biomarker was detected in 10 of 11 (91%) patients with non-SLN metastases. Conclusion: The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.

Original languageEnglish (US)
Pages (from-to)4105-4110
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number14
DOIs
StatePublished - Jul 15 2007
Externally publishedYes

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Circulating Neoplastic Cells
Lymph Nodes
Tumor Biomarkers
Breast Neoplasms
Neoplasm Metastasis
Reverse Transcription
N-Acetylgalactosaminyltransferases
Odds Ratio
Confidence Intervals
Melanoma-Specific Antigens
Polymerase Chain Reaction
Volunteers
Healthy Volunteers
Research Design
Multivariate Analysis
Messenger RNA
Sentinel Lymph Node

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nakagawa, T., Martinez, S. R., Goto, Y., Koyanagi, K., Kitago, M., Shingai, T., ... Hoon, D. S. B. (2007). Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes. Clinical Cancer Research, 13(14), 4105-4110. https://doi.org/10.1158/1078-0432.CCR-07-0419

Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes. / Nakagawa, Taku; Martinez, Steve R.; Goto, Yasufumi; Koyanagi, Kazuo; Kitago, Minoru; Shingai, Tatsushi; Elashoff, David A.; Ye, Xing; Singer, Frederick R.; Giuliano, Armando E.; Hoon, Dave S B.

In: Clinical Cancer Research, Vol. 13, No. 14, 15.07.2007, p. 4105-4110.

Research output: Contribution to journalArticle

Nakagawa, T, Martinez, SR, Goto, Y, Koyanagi, K, Kitago, M, Shingai, T, Elashoff, DA, Ye, X, Singer, FR, Giuliano, AE & Hoon, DSB 2007, 'Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes', Clinical Cancer Research, vol. 13, no. 14, pp. 4105-4110. https://doi.org/10.1158/1078-0432.CCR-07-0419
Nakagawa, Taku ; Martinez, Steve R. ; Goto, Yasufumi ; Koyanagi, Kazuo ; Kitago, Minoru ; Shingai, Tatsushi ; Elashoff, David A. ; Ye, Xing ; Singer, Frederick R. ; Giuliano, Armando E. ; Hoon, Dave S B. / Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 14. pp. 4105-4110.
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abstract = "Purpose: Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status. Experimental Design: Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normalhealthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status. Results: CTCs were detected in 39 of 90 (43{\%}) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29{\%}) stage I patients, 19 of 42 (45{\%}) stage II patients, and 10 of 13 (77{\%}) stage III patients. In multivariate analysis, only lymphovascular invasion and ≥2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95{\%} confidence interval (95{\%} CI), 3.52-43.77, P < 0.0001; and OR, 3.88; 95{\%} CI, 1.69-8.89, P = 0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P = 0.0004). At least one CTC biomarker was detected in 10 of 11 (91{\%}) patients with non-SLN metastases. Conclusion: The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.",
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T1 - Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes

AU - Nakagawa, Taku

AU - Martinez, Steve R.

AU - Goto, Yasufumi

AU - Koyanagi, Kazuo

AU - Kitago, Minoru

AU - Shingai, Tatsushi

AU - Elashoff, David A.

AU - Ye, Xing

AU - Singer, Frederick R.

AU - Giuliano, Armando E.

AU - Hoon, Dave S B

PY - 2007/7/15

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N2 - Purpose: Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status. Experimental Design: Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normalhealthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status. Results: CTCs were detected in 39 of 90 (43%) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29%) stage I patients, 19 of 42 (45%) stage II patients, and 10 of 13 (77%) stage III patients. In multivariate analysis, only lymphovascular invasion and ≥2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95% confidence interval (95% CI), 3.52-43.77, P < 0.0001; and OR, 3.88; 95% CI, 1.69-8.89, P = 0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P = 0.0004). At least one CTC biomarker was detected in 10 of 11 (91%) patients with non-SLN metastases. Conclusion: The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.

AB - Purpose: Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status. Experimental Design: Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normalhealthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status. Results: CTCs were detected in 39 of 90 (43%) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29%) stage I patients, 19 of 42 (45%) stage II patients, and 10 of 13 (77%) stage III patients. In multivariate analysis, only lymphovascular invasion and ≥2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95% confidence interval (95% CI), 3.52-43.77, P < 0.0001; and OR, 3.88; 95% CI, 1.69-8.89, P = 0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P = 0.0004). At least one CTC biomarker was detected in 10 of 11 (91%) patients with non-SLN metastases. Conclusion: The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.

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