title: Improved Circulating Tumor Cell Detection by a Combined EpCAM and MCAM CellSearch Enrichment Approach in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy.
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.
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands. w.onstenk@erasmusmc.nl.
authors.forename: Wendy
authors.initials: W
authors.lastname: Onstenk
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jaco
authors.initials: J
authors.lastname: Kraan
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Bianca
authors.initials: B
authors.lastname: Mostert
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Mieke M
authors.initials: MM
authors.lastname: Timmermans
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands. Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ayoub
authors.initials: A
authors.lastname: Charehbili
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kroep
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Johan W R
authors.initials: JW
authors.lastname: Nortier
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: van de Ven
authors.affiliation: Department of Medical Oncology, Amphia Hospital, Breda, the Netherlands.
authors.forename: Joan B
authors.initials: JB
authors.lastname: Heijns
authors.affiliation: Department of Internal Medicine, Deventer Hospital, Deventer, the Netherlands.
authors.forename: Lonneke W
authors.initials: LW
authors.lastname: Kessels
authors.affiliation: Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Hanneke W M
authors.initials: HW
authors.lastname: van Laarhoven
authors.affiliation: Department of Internal Medicine, Reinier de Graaf Hospital, Delft, the Netherlands.
authors.forename: Monique M E M
authors.initials: MM
authors.lastname: Bos
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Gratama
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051929:CD146 Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; C497902:MCAM protein, human