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

DOI: 10.1007/s00404-011-1954-2

Cite this article as:
Rack, B., Jückstock, J., Günthner-Biller, M. et al. Arch Gynecol Obstet (2012) 285: 485. doi:10.1007/s00404-011-1954-2

Abstract

Purpose

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.

Conclusion

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.

Keywords

Breast cancerRecurrence-free follow-upIsolated tumor cellsMinimal residual diseaseTrastuzumab treatment

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