title: Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker.
abstract: BACKGROUND
  This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients.
  
  
  METHODS
  Sixty HER2-positive MBC patients were enrolled in the present study. Before the initiation of systemic treatment, CTCs from 7.5 ml of blood were analyzed using the CellSearch system. The progression-free survival (PFS) of the patients was estimated using Kaplan-Meier survival curves.
  
  
  RESULTS
  CTCs were detected in 45% (27/60) of the patients, who had shorter median PFS than those without CTCs (2.5 vs. 7.5 months, P=0.0125). Furthermore, referring to the standard HER2 testing that uses immunohistochemistry (IHC), we proposed a CTC HER2-positive criterion, defined as >30% of CTCs over-expressing HER2. Among patients undergoing anti-HER2 therapy, those with HER2-positive CTCs had longer PFS (8.8 vs. 2.5 months, P=0.002). Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P=0.001). Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P=0.499).
  
  
  CONCLUSIONS
  Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients. To test this idea, additional large cohort, multi-center and prospective clinical trials are needed.
authors.affiliation: Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, No.8 Dongdajie, Beijing, 100071, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhang
authors.forename: Haixu
authors.initials: H
authors.lastname: Hu
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
authors.forename: Shikai
authors.initials: S
authors.lastname: Wu
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Zefei
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human