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Erschienen in: Archives of Gynecology and Obstetrics 2/2012

01.02.2012 | Gynecologic Oncology

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

verfasst von: 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

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 2/2012

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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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Metadaten
Titel
Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients
verfasst von
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
Publikationsdatum
01.02.2012
Verlag
Springer-Verlag
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 2/2012
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-011-1954-2

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