title: Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients.
abstract: OBJECTIVE
  Isolated tumor cells (ITC) in the bone marrow of breast cancer patients increase the risk of recurrence and decrease survival, both at primary diagnosis and during follow-up. We tested the efficacy of trastuzumab in clearing HER2/neu-positive ITC from the marrow of patients completing primary treatment.
  
  
  METHODS
  Ten recurrence-free patients with persistent HER2/neu-positive ITC after routine adjuvant treatment received trastuzumab 6 mg/kg q3w for 12 months in a non-randomized pilot phase II interventional study. Bone marrow ITC HER2/neu status was evaluated at baseline, after treatment for 3, 6 and 12 months, and yearly thereafter, in combination with clinical follow-up. Median follow-up was 23 (15-64) months after baseline bone marrow aspiration.
  
  
  RESULTS
  Trastuzumab for 12 months eradicated HER2/neu-positive ITC from bone marrow in all patients (P = 0.002) and significantly reduced the number of ITC-positive patients (P = 0.031). However, HER2/neu-negative ITC persisted in three patients immediately after treatment and were detected at yearly bone marrow aspiration in five patients. Two patients with ITC counts ≥5 at yearly follow-up developed metastases and one died.
  
  
  CONCLUSIONS
  This is the first evidence that trastuzumab is effective in clearing HER2/neu-positive cells from bone marrow during recurrence-free follow-up in breast cancer patients. It also suggests, thanks to the antigen shift phenomenon, an important prognostic role for HER2/neu expression on marrow ITC as a real-time biopsy. However, treatment was mainly effective in patients with HER2/neu-positive ITC. Given the heterogeneity of minimal residual disease, these patients might benefit from a combination of targeted treatment approaches.
authors: Department of Gynecology and Obstetrics, Klinikum Innenstadt, Ludwig-Maximilians-Universitaet Muenchen, Maistr. 11, 80337 Munich, Germany. brigitte.rack@med.uni-muenchen.de
authors: Brigitte
authors: B
authors: Rack
authors: Julia
authors: J
authors: Jückstock
authors: Maria
authors: M
authors: Günthner-Biller
authors: Ulrich
authors: U
authors: Andergassen
authors: Julia
authors: J
authors: Neugebauer
authors: Philip
authors: P
authors: Hepp
authors: Alexandra
authors: A
authors: Schoberth
authors: Doris
authors: D
authors: Mayr
authors: Thomas
authors: T
authors: Zwingers
authors: Christian
authors: C
authors: Schindlbeck
authors: Klaus
authors: K
authors: Friese
authors: Wolfgang
authors: W
authors: Janni
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D010865:Pilot Projects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab