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

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

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. DTCs in bone marrow were enumerated using the EPCAM-based immunomagnetic enrichment and flow cytometry (IE/FC) a...

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Veröffentlicht in:Clinical cancer research 2019-09, Vol.25 (17), p.5388-5397
Hauptverfasser: Magbanua, Mark Jesus M, Yau, Christina, Wolf, Denise M, Lee, Jin Sun, Chattopadhyay, Aheli, Scott, Janet H, Bowlby-Yoder, Erin, Hwang, E Shelley, Alvarado, Michael, Ewing, Cheryl A, Delson, Amy L, Van't Veer, Laura J, Esserman, Laura, Park, John W
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container_end_page 5397
container_issue 17
container_start_page 5388
container_title Clinical cancer research
container_volume 25
creator Magbanua, Mark Jesus M
Yau, Christina
Wolf, Denise M
Lee, Jin Sun
Chattopadhyay, Aheli
Scott, Janet H
Bowlby-Yoder, Erin
Hwang, E Shelley
Alvarado, Michael
Ewing, Cheryl A
Delson, Amy L
Van't Veer, Laura J
Esserman, Laura
Park, John W
description 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. 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. 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). 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.
doi_str_mv 10.1158/1078-0432.CCR-18-3888
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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). 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). 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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). 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). 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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. 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). 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title Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer
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