Abstract
e22106 Background: Using the CellSearch System (Veridex, USA), ≥1 CTC/7.5 mL of peripheral blood is found in ~20% of primary breast cancer (BC) patients. However, epithelial cell adhesion molecule (EpCAM)-negative CTCs may be missed. We previously showed that a subset of BC cell lines lacks EpCAM, but does express melanoma cell adhesion molecule (MCAM) and that MCAM-positive CTCs (M-CTCs) do occur in metastatic breast cancer patients. In a side-study of the NEOZOTAC trial, a randomized study comparing neoadjuvant chemotherapy (NAC) with or without zoledronic acid in stage II/III BC, we investigated whether combined enrichment with EpCAM and MCAM increases the CTC detection rate. Besides, we hypothesized that CTC counts would correlate with pathological complete response (pCR) to NAC. Additionally, as exploratory study, circulated endothelial cells (CECs) were measured. Methods: At baseline and after the 1st chemotherapy cycle, blood was drawn from all patients in the NEOZOTAC trial who gave additional informed consent. The CellSearch System was used to count EpCAM-positive CTCs (E-CTCs) and M-CTCs. For the latter, the anti-EpCAM-ferrofluid was replaced by an anti-MCAM-ferrofluid (both Veridex). CECs were measured using flow cytometry. Results: At baseline, blood was received from 73 patients; ≥1 E-CTCs and M-CTCs were detected in 14/73 (19%, median 1) and 8/68 (12%, median 1), respectively. Combining both counts, ≥1 CTCs were detected in 17/68 (25%) of patients (p=0.01). After 1 chemotherapy cycle, E-CTCs, M-CTCs and overall CTCs were detected in 9/47 (19%), 7/45 (16%), and 13/44 (30%; p<0.01) patients. Median CEC count was 43 at baseline and 142 after cycle 1 (p<0.001). No differences in CTC and CEC count were found between the treatment arms. Baseline CTC counts, nor changes in counts, were associated with pCR. Conclusions: Combined enrichment of CTCs with EpCAM and MCAM significantly increased CTC detection rates in stage II/III BC with about 10%. CTC counts were not associated with pCR to NAC. Associations with disease free survival will follow when available.
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