title: Efficacy control of therapy using circulating epithelial tumor cells (CETC) as "liquid biopsy": trastuzumab in HER2/neu-positive breast carcinoma.
abstract: OBJECTIVE
  The majority of targeted personalized cancer therapies are effective only in part of the patients, and most of these drugs are excessively expensive. Therefore, methods are urgently required, which reveal already early during treatment, whether the therapy is effective. In the present report, monitoring of circulating epithelial tumor cells (CETC) was used as a timely control of trastuzumab therapy in patients with HER2/neu-positive breast cancer.
  
  
  METHODS
  Seventy-nine sequential HER2/neu-positive breast cancer patients, 35 without trastuzumab, and 36 treated with 1 year of trastuzumab treatment were included. CETC from unseparated white blood cells stained with FITC-anti-EpCAM were analyzed repeatedly during chemotherapy and between 2 and 10 times during 1 year of maintenance treatment or observation.
  
  
  RESULTS
  Patients treated with trastuzumab had a better relapse-free survival than patients without trastuzumab treatment during the first 2-4 years of follow-up. Decrease in numbers or no change versus highly variable numbers or increase (fivefold or more) allowed to discriminate highly significantly and clearly (P < 0.0001, hazard ratio 5.5) between patients with a low or high risk of relapse. An increase in CETC was accompanied by an increasing portion of cells containing a very high number of HER2/neu gene amplificates.
  
  
  CONCLUSIONS
  Analysis of the behavior of CETC can, in the future, contribute to evaluate the efficacy of targeted therapy early during the course of the disease, sparing patients unnecessary treatment but also to reduce the costs for the health system and to downsize the extent and length of clinical studies.
authors: Department of Experimental Hematology and Oncology, Clinic for Internal Medicine II, Friedrich Schiller University, Jena, Erlanger Allee 101, 07747, Jena, Germany. Katharina.pachmann@med.uni-jena.de
authors: Katharina
authors: K
authors: Pachmann
authors: O
authors: O
authors: Camara
authors: T
authors: T
authors: Kroll
authors: M
authors: M
authors: Gajda
authors: A K
authors: AK
authors: Gellner
authors: J
authors: J
authors: Wotschadlo
authors: I B
authors: IB
authors: Runnebaum
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000097:blood; D001706:Biopsy / Q000379:methods; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human