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

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.