Archives of Gynecology and Obstetrics

, Volume 285, Issue 2, pp 485–492

Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients

  • Brigitte Rack
  • Julia Jückstock
  • Maria Günthner-Biller
  • Ulrich Andergassen
  • Julia Neugebauer
  • Philip Hepp
  • Alexandra Schoberth
  • Doris Mayr
  • Thomas Zwingers
  • Christian Schindlbeck
  • Klaus Friese
  • Wolfgang Janni
Gynecologic Oncology



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.


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.


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.


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.


Breast cancer Recurrence-free follow-up Isolated tumor cells Minimal residual disease Trastuzumab treatment 


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Brigitte Rack
    • 1
  • Julia Jückstock
    • 1
  • Maria Günthner-Biller
    • 1
  • Ulrich Andergassen
    • 1
  • Julia Neugebauer
    • 1
  • Philip Hepp
    • 6
  • Alexandra Schoberth
    • 2
  • Doris Mayr
    • 5
  • Thomas Zwingers
    • 4
  • Christian Schindlbeck
    • 3
  • Klaus Friese
    • 1
  • Wolfgang Janni
    • 6
  1. 1.Department of Gynecology and Obstetrics, Klinikum InnenstadtLudwig-Maximilians-Universitaet MuenchenMunichGermany
  2. 2.TRION Research GmbHMartinsriedGermany
  3. 3.Klinikum TraunsteinTraunsteinGermany
  4. 4.Estimate GmbHAugsburgGermany
  5. 5.Pathologisches InstitutLudwig-Maximilians-UniversitaetMunichGermany
  6. 6.Department of Gynecology and Obstetrics, Heinrich-Heine-UniversitaetDüsseldorfGermany

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