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


METHODS
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.


CONCLUSIONS
The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.
Nakagawa
Taku
T
Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California 90404, USA.
Martinez
Steve R
SR
Goto
Yasufumi
Y
Koyanagi
Kazuo
K
Kitago
Minoru
M
Shingai
Tatsushi
T
Elashoff
David A
DA
Ye
Xing
X
Singer
Frederick R
FR
Giuliano
Armando E
AE
Hoon
Dave S B
DS
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D021701:Sentinel Lymph Node Biopsy
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone