title: Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer.
abstract: Before using circulating tumor cells (CTCs) as liquid biopsy, insight into molecular discrepancies between CTCs and primary tumors is essential. We characterized CellSearch-enriched CTCs from 62 metastatic breast cancer (MBC) patients with ≥5 CTCs starting first-line systemic treatment. Expression levels of 35 tumor-associated, CTC-specific genes, including ESR1, coding for the estrogen receptor (ER), were measured by reverse transcription quantitative polymerase chain reaction and correlated to corresponding primary tumors. In 30 patients (48%), gene expression profiles of 35 genes were discrepant between CTCs and the primary tumor, but this had no prognostic consequences. In 15 patients (24%), the expression of ER was discrepant. Patients with ER-negative primary tumors and ER-positive CTCs had a longer median TTS compared to those with concordantly ER-negative CTCs (8.5 versus 2.1 months, P = 0.05). From seven patients, an axillary lymph node metastasis was available. In two patients, the CTC profiles better resembled the lymph node metastasis than the primary tumor. Our findings suggest that molecular discordances between CTCs and primary tumors frequently occur, but that this bears no prognostic consequences. Alterations in ER-status between primary tumors and CTCs might have prognostic implications.
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: w.onstenk@erasmusmc.nl.
authors: Wendy
authors: W
authors: Onstenk
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Anieta M
authors: AM
authors: Sieuwerts
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Marleen
authors: M
authors: Weekhout
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Bianca
authors: B
authors: Mostert
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Esther A
authors: EA
authors: Reijm
authors: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Carolien H M
authors: CH
authors: van Deurzen
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Joan B
authors: JB
authors: Bolt-de Vries
authors: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus and Department of Oncology, University of Antwerp, Antwerp, Belgium.
authors: Dieter J
authors: DJ
authors: Peeters
authors: Department of Internal Medicine, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
authors: Paul
authors: P
authors: Hamberg
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Caroline
authors: C
authors: Seynaeve
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Agnes
authors: A
authors: Jager
authors: Department of Internal Medicine, Ikazia Hospital, Rotterdam, The Netherlands.
authors: Felix E
authors: FE
authors: de Jongh
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Marcel
authors: M
authors: Smid
authors: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus and Department of Oncology, University of Antwerp, Antwerp, Belgium.
authors: Luc Y
authors: LY
authors: Dirix
authors: Department of Internal Medicine, IJsselland Hospital, Capelle aan den IJssel, The Netherlands.
authors: Diederik F S
authors: DF
authors: Kehrer
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Anne
authors: A
authors: van Galen
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Raquel
authors: R
authors: Ramirez-Moreno
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Jaco
authors: J
authors: Kraan
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Mai
authors: M
authors: Van
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Jan W
authors: JW
authors: Gratama
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: John W M
authors: JW
authors: Martens
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: John A
authors: JA
authors: Foekens
authors: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Stefan
authors: S
authors: Sleijfer
mesh_terms: D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics; D012189:Retrospective Studies; D059467:Transcriptome
chemical_list: D011960:Receptors, Estrogen
keywords: CellSearch; Circulating tumor cells; Estrogen receptor; Gene expression; Metastatic breast cancer; Prognostic