Abstract
Circulating tumor cells (CTC) are detected by the CellSearch System in 20% to 25% of patients with primary breast cancer (pBC). To improve CTC detection, we investigated melanoma cell adhesion molecule (MCAM) as enrichment marker next to epithelial cell adhesion molecule (EpCAM) and tested the clinical relevance of MCAM-positive CTCs in patients with HER2-negative stage II/III pBC starting neoadjuvant chemotherapy (NAC) in the NEOZOTAC trial. Using the CellSearch System, EpCAM-positive and MCAM-positive CTCs were separately enriched from 7.5 mL blood, at baseline and after the first NAC cycle. Circulating endothelial cells (CEC) were measured using flow cytometry. Primary objective was to improve the CTC detection rate to ≥ 40% combining EpCAM/MCAM. Correlations of CTC and CEC counts and pathologic complete response (pCR) were also explored. At baseline, we detected EpCAM-positive and MCAM-positive CTCs in 12 of 68 (18%) and 8 of 68 (12%) patients, respectively. After one cycle, this was 7 of 44 (16%) and 7 of 44 (16%) patients, respectively. The detection rate improved from 18% at baseline and 16% after one cycle with EpCAM to 25% (P = 0.08) and 30% (P = 0.02), respectively, with EpCAM/MCAM. No patients with MCAM-positive CTCs versus 23% of patients without MCAM-positive CTCs at baseline achieved pCR (P = 0.13). EpCAM-positive CTCs and CEC counts were not correlated to pCR. Combined EpCAM/MCAM CellSearch enrichment thus increased the CTC detection rate in stage II/III pBC. We found no associations of CTC and CEC counts with pCR to NAC. The clinical relevance of MCAM-positive CTCs deserves further study.
Highlights
A circulating tumor cell (CTC) count from peripheral blood as measured by the FDA-approved CellSearch System (Janssen Diagnostics) is a strong prognostic factor in both primary and meta-Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online.Ó2014 American Association for Cancer Research.static breast cancers [1]
The CTC detection rate increased from 18%
We investigated melanoma cell adhesion molecule (MCAM) as additional CellSearch enrichment marker next to epithelial cell adhesion molecule (EpCAM) to improve the CTC capture rate in stage II/III breast cancer
Summary
A circulating tumor cell (CTC) count from peripheral blood as measured by the FDA-approved CellSearch System (Janssen Diagnostics) is a strong prognostic factor in both primary and meta-Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).Ó2014 American Association for Cancer Research.static breast cancers [1]. 70% of patients with metastatic breast cancer (mBC) have !1 CTC/7.5 mL of blood, in primary breast cancer (pBC), this proportion is only as low as 20% to 25% [1,2,3,4,5,6]. In both cases, the presence of CTCs is associated with poor prognosis. For mBC, patients with !5 CTCs/7.5 mL blood have significantly shorter median progression-free survival (PFS) and overall survival (OS) compared with patients with
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