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

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

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.

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Acknowledgments

Supported by a grant from Roche and the Friedrich-Baur-Stiftung, Munich, Germany. Neither Roche nor the Friedrich-Baur-Stiftung had any influence on the study design, collection, analysis and interpretation of the data or writing of the manuscript. The authors are sincerely grateful to Heidi Coleman for her editorial support.

Conflict of interest

Brigitte Rack, Christian Schindlbeck and Wolfgang Janni have received research funding and speakers honoraria from Roche. Julia Jückstock, Margit Günthner-Biller, Ulrich Andergassen, Julia Neugebauer, Philip Hepp, Alexandra Schoberth, Doris Mayr, Thomas Zwingers and Klaus Friese have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Klinikum Innenstadt, Ludwig-Maximilians-Universitaet Muenchen, Maistr. 11, 80337, Munich, Germany

    Brigitte Rack, Julia Jückstock, Maria Günthner-Biller, Ulrich Andergassen, Julia Neugebauer & Klaus Friese

  2. TRION Research GmbH, Am Klopferspitz 19, 82152, Martinsried, Germany

    Alexandra Schoberth

  3. Klinikum Traunstein, Cuno-Niggl-Straße 3, 83278, Traunstein, Germany

    Christian Schindlbeck

  4. Estimate GmbH, Konrad-Adenauer-Allee 1, 86150, Augsburg, Germany

    Thomas Zwingers

  5. Pathologisches Institut, Ludwig-Maximilians-Universitaet, Thalkirchnerstr. 36, 80337, Munich, Germany

    Doris Mayr

  6. Department of Gynecology and Obstetrics, Heinrich-Heine-Universitaet, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Philip Hepp & Wolfgang Janni

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  1. Brigitte Rack
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Correspondence to Brigitte Rack.

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Rack, B., Jückstock, J., Günthner-Biller, M. et al. Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients. Arch Gynecol Obstet 285, 485–492 (2012). https://doi.org/10.1007/s00404-011-1954-2

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  • DOI: https://doi.org/10.1007/s00404-011-1954-2

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