Abstract
IntroductionThe detection of circulating tumour cells (CTCs) in the peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are promising prognostic tools for risk stratification in early breast cancer. There is, however, a need for further validation of these techniques in larger patient cohorts with adequate follow-up periods.MethodsWe assayed CTCs and DTCs at primary surgery in 733 stage I or II breast cancer patients with a median follow-up time of 7.6 years. CTCs were detected in samples of peripheral blood mononuclear cells previously stored in liquid-nitrogen using a previously-developed multi-marker quantitative PCR (QPCR)-based assay. DTCs were detected in bone marrow samples by immunocytochemical analysis using anti-cytokeratin antibodies.ResultsCTCs were detected in 7.9% of patients, while DTCs were found in 11.7%. Both CTC and DTC positivity predicted poor metastasis-free survival (MFS) and breast cancer-specific survival (BCSS); MFS hazard ratio (HR) = 2.4 (P < 0.001)/1.9 (P = 0.006), and BCSS HR = 2.5 (P < 0.001)/2.3 (P = 0.01), for CTC/DTC status, respectively). Multivariate analyses demonstrated that CTC status was an independent prognostic variable for both MFS and BCSS. CTC status also identified a subset of patients with significantly poorer outcome among low-risk node negative patients that did not receive adjuvant systemic therapy (MFS HR 2.3 (P = 0.039), BCSS HR 2.9 (P = 0.017)). Using both tests provided increased prognostic information and indicated different relevance within biologically dissimilar breast cancer subtypes.ConclusionsThese results support the use of CTC analysis in early breast cancer to generate clinically useful prognostic information.
Highlights
The detection of circulating tumour cells (CTCs) in the peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are promising prognostic tools for risk stratification in early breast cancer
This sample set generated comparable tumour marker weights to the metastatic patients. This analysis demonstrated that the assay gave a positive CTC score when as few as one tumour cell per mL was present in the sample
Circulating tumour cell status versus disseminated tumour cell status Previously, we reported the clinical significance of DTC status in this patient cohort by immunocytochemical detection of cytokeratin-positive cells [1]
Summary
The detection of circulating tumour cells (CTCs) in the peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are promising prognostic tools for risk stratification in early breast cancer. In recent years breast cancer survival rates have been steadily increasing, partly due to earlier diagnoses as a result of increased awareness and widespread mammography screening programmes. Despite these advances, approximately one-third of patients will develop distant metastasis, which represents the terminal step in the progression of the disease. There remains a need for good quality studies to confirm the clinical relevance of CTCs in larger patient cohorts, in comparison to DTCs. So far relatively few such studies in early breast cancer have included mature outcome data. Whether CTC detection could replace DTC detection is still an open question, and the value of CTCs versus DTCs may differ among patients as a consequence of different tumour biology and/or dissemination characteristics
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