Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer

Purpose: We examined the prognostic impact of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) detected at the time of surgery in 742 untreated patients with early breast cancer.

Experimental Design: DTCs in bone marrow were enumerated using the EPCAM-based immunomagnetic enrichment and flow cytometry (IE/FC) assay. CTCs in blood were enumerated either by IE/FC or CellSearch. Median follow-up was 7.1 years for distant recurrence-free survival (DRFS) and 9.1 years for breast cancer-specific survival (BCSS) and overall survival (OS). Cox regressions were used to estimate hazard ratios for DRFS, BCSS, and OS in all patients, as well as in hormone receptor-positive (HR-positive, 87%) and HR-negative (13%) subsets.

Results: In multivariate models, CTC positivity by IE/FC was significantly associated with reduced BCSS in both all ( = 288; = 0.0138) and HR-positive patients ( = 249; = 0.0454). CTC positivity by CellSearch was significantly associated with reduced DRFS in both all ( = 380; = 0.0067) and HR-positive patients ( = 328; = 0.0002). DTC status, by itself, was not prognostic; however, when combined with CTC status by IE/FC ( = 273), double positivity (CTC+/DTC+, 8%) was significantly associated with reduced DRFS ( = 0.0270), BCSS ( = 0.0205), and OS ( = 0.0168). In HR-positive patients, double positivity (9% of 235) was significantly associated with reduced DRFS ( = 0.0285), BCSS ( = 0.0357), and OS ( = 0.0092).

Conclusions: Detection of CTCs in patients with HR-positive early breast cancer was an independent prognostic factor for DRFS (using CellSearch) and BCSS (using IE/FC). Simultaneous detection of DTCs provided additional prognostic power for outcome, including OS.