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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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