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. 2011 Jun 7;104(12):1913-9.
doi: 10.1038/bjc.2011.164. Epub 2011 May 17.

A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer

T J Molloy  1 , L A Devriese, H H Helgason, A J Bosma, M Hauptmann, E E Voest, J H M Schellens, L J van't Veer
Affiliations

A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer

T J Molloy et al. Br J Cancer. .

Abstract

Background: The detection of circulating tumour cells (CTCs) has been linked with poor prognosis in advanced breast cancer. Relatively few studies have been undertaken to study the clinical relevance of CTCs in early-stage breast cancer.

Methods: In a prospective study, we evaluated CTCs in the peripheral blood of 82 early-stage breast cancer patients. Control groups consisted of 16 advanced breast cancer patients and 45 healthy volunteers. The CTC detection was performed using ErbB2/EpCAM immunomagnetic tumour cell enrichment followed by multimarker quantitative PCR (QPCR). The CTC status and common clinicopathological factors were correlated to relapse-free, breast cancer-related and overall survival.

Results: Circulating tumour cells were detected in 16 of 82 (20%) patients with early-stage breast cancer and in 13 out of 16 (81%) with advanced breast cancer. The specificity was 100%. The median follow-up time was 51 months (range: 17-60). The CTC positivity in early-stage breast cancer patients resulted in significantly poorer relapse-free survival (log rank test: P=0.003) and was an independent predictor of relapse-free survival (multivariate hazard ratio=5.13, P=0.006, 95% CI: 1.62-16.31).

Conclusion: The detection of CTCs in peripheral blood of early-stage breast cancer patients provided prognostic information for relapse-free survival.

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Figures

Figure 1
Figure 1
Quadratic discriminant analysis (QDA) values incorporating the expression of the four marker genes CK19, p1B, EGP and MmGl measured in the peripheral blood of healthy controls (n=45; open circles), early-stage breast cancer (BC) patients (n=82; triangles) and advanced BC patients (n=16; closed circles). The median expression levels for the QDA are indicated by a horizontal line (healthy controls=−1.16, early-stage BC patients=−1.16, advanced breast cancer patients=2.39).
Figure 2
Figure 2
Kaplan–Meier survival curve for relapse-free survival of early-stage breast cancer patients (n=82) who were CTC negative (n=66) or positive (n=16) at diagnosis. CTC-positive patients had a significantly poorer relapse-free survival than CTC-negative patients (univariate hazard ratio=4.72; 95% CI: 1.52–14.66; log rank test P=0.003). The number of patients at risk at each time point (months) are indicated for the CTC-negative (black) and CTC-positive (grey) groups. Abbreviations: CTC-positive or CTC-negative=positive or negative circulating tumour cell status according to quadratic discriminant analysis (QDA) score; FU=follow-up.
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