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

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 normal healthy 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 >or=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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 14 Pg. 4105-10 (Jul 15 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17634536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Ki-67 Antigen
• RNA, Neoplasm
• Receptors, Estrogen
• Receptors, Progesterone
• Receptor, ErbB-2

Topics

• Biomarkers, Tumor (analysis)
• Breast Neoplasms (blood, genetics, pathology)
• Cell Line, Tumor
• Female
• Humans
• Ki-67 Antigen (analysis)
• Lymphatic Metastasis (pathology)
• Middle Aged
• Neoplasm Staging
• RNA, Neoplasm (genetics, isolation & purification)
• Receptor, ErbB-2 (analysis)
• Receptors, Estrogen (analysis)
• Receptors, Progesterone (analysis)
• Sentinel Lymph Node Biopsy