title: An 8-gene mRNA expression profile in circulating tumor cells predicts response to aromatase inhibitors in metastatic breast cancer patients.
abstract: BACKGROUND
  Molecular characterization of circulating tumor cells (CTC) is promising for personalized medicine. We aimed to identify a CTC gene expression profile predicting outcome to first-line aromatase inhibitors in metastatic breast cancer (MBC) patients.
  
  
  METHODS
  CTCs were isolated from 78 MBC patients before treatment start. mRNA expression levels of 96 genes were measured by quantitative reverse transcriptase polymerase chain reaction. After applying predefined exclusion criteria based on lack of sufficient RNA quality and/or quantity, the data from 45 patients were used to construct a gene expression profile to predict poor responding patients, defined as disease progression or death <9 months, by a leave-one-out cross validation.
  
  
  RESULTS
  Of the 45 patients, 19 were clinically classified as poor responders. To identify them, the 75% most variable genes were used to select genes differentially expressed between good and poor responders. An 8-gene CTC predictor was significantly associated with outcome (Hazard Ratio [HR] 4.40, 95% Confidence Interval [CI]: 2.17-8.92, P < 0.001). This predictor identified poor responding patients with a sensitivity of 63% and a positive predictive value of 75%, while good responding patients were correctly predicted in 85% of the cases. In multivariate Cox regression analysis, including CTC count at baseline, the 8-gene CTC predictor was the only factor independently associated with outcome (HR 4.59 [95% CI: 2.11-9.56], P < 0.001). This 8-gene signature was not associated with outcome in a group of 71 MBC patients treated with systemic treatments other than AI.
  
  
  CONCLUSIONS
  An 8-gene CTC predictor was identified which discriminates good and poor outcome to first-line aromatase inhibitors in MBC patients. Although results need to be validated, this study underscores the potential of molecular characterization of CTCs.
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Esther A
authors.initials: EA
authors.lastname: Reijm
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, 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, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smid
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Joan Bolt-de
authors.initials: JB
authors.lastname: Vries
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, 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, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Onstenk
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus and Department of Oncology, University of Antwerp, Antwerp, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Peeters
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus and Department of Oncology, University of Antwerp, Antwerp, Belgium.
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Seynaeve
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.affiliation: Department of Internal Medicine, Ikazia Hospital, Rotterdam, The Netherlands.
authors.forename: Felix E
authors.initials: FE
authors.lastname: de Jongh
authors.affiliation: Department of Internal Medicine, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hamberg
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: van Galen
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, 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, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Maurice P H M
authors.initials: MP
authors.lastname: Jansen
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, 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, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, 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, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, 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, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
authors.forename: Els M J J
authors.initials: EM
authors.lastname: Berns
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC - Cancer Institute, Erasmus University Medical Center, Room He 116, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands. s.sleijfer@erasmusmc.nl.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011379:Prognosis; D018570:Risk Assessment
chemical_list: D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor